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Clinical Trial Results:
A Phase 3, Randomized, Double Blind, Placebo and Active-Controlled, Multicenter, Parallel-Group Study of the Analgesic Efficacy and Safety of Tanezumab in Adult Subjects with Chronic low Back Pain

Summary
EudraCT number	2012-005495-34
Trial protocol	SE   HU   DK   ES
Global end of trial date	20 Dec 2018
Results information
Results version number	v1
This version publication date	04 Jan 2020
First version publication date	04 Jan 2020
Other versions	v2

Trial information Top of page
Trial identification
Sponsor protocol code	A4091059
Additional study identifiers
ISRCTN number	-
US NCT number	NCT02528253
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Pfizer, Inc.
Sponsor organisation address	235 E 42nd Street, New York, United States, NY 10017
Public contact	Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
Scientific contact	Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	20 Dec 2018
Is this the analysis of the primary completion data?	No
Global end of trial reached?	Yes
Global end of trial date	20 Dec 2018
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	Demonstrate superior analgesic efficacy of tanezumab 10 mg and 5 mg administered subcutaneously (SC) every 8 weeks compared to placebo at Week 16.
Protection of trial subjects	The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	18 Aug 2015
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Canada: 80
Country: Number of subjects enrolled	France: 1
Country: Number of subjects enrolled	Hungary: 24
Country: Number of subjects enrolled	Japan: 129
Country: Number of subjects enrolled	Korea, Republic of: 16
Country: Number of subjects enrolled	Spain: 61
Country: Number of subjects enrolled	Sweden: 11
Country: Number of subjects enrolled	United States: 1503
Worldwide total number of subjects	1825
EEA total number of subjects	97
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	1607
From 65 to 84 years	218
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Study enrolled a total of 1832 subjects. However subject disposition has been provided for 1825 treated subjects.
Pre-assignment
Screening details	Treatment period for investigation product was up to Week 56.Safety follow up period started at Week 64,thus Week 64 and Week 80 time points are during safety follow up period.% reduction in low back pain intensity (LBPI) and subjects global assessment (PGA) 2-point reduction are efficacy measures and not applicable during safety follow up.
Period 1
Period 1 title	Overall Study (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Investigator, Subject
Arms
Are arms mutually exclusive	Yes
Arm title	Placebo Followed by Tanezumab 5 mg
Arm description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously (SC) once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol prolonged release (PR), orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (greater than equal to [>=] 30 percentage [%] reduction in average (low back pain intensity [LBPI]) score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 milligram (mg), SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Arm type	Experimental
Investigational medicinal product name	Tanezumab
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	Subject received tanezumab injection administered subcutaneously (SC) once every 8 weeks from Day 1.
Arm title	Placebo Followed by Tanezumab 10 mg
Arm description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 percentage % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Arm type	Experimental
Investigational medicinal product name	Tanezumab
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	Subject received tanezumab injection administered subcutaneously (SC) once every 8 weeks from Day 1.
Arm title	Tanezumab 5 mg
Arm description	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Arm type	Experimental
Investigational medicinal product name	Tanezumab
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	Subject received tanezumab injection administered subcutaneously (SC) once every 8 weeks from Day 1.
Arm title	Tanezumab 10 mg
Arm description	Tanezumab (RN624 or PF-04383119) 10 mg injection administered SC once every 8 weeks from Day 1, and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Arm type	Experimental
Investigational medicinal product name	Tanezumab
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	Subject received tanezumab injection administered subcutaneously (SC) once every 8 weeks from Day 1.
Arm title	Tramadol
Arm description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 56.
Arm type	Experimental
Investigational medicinal product name	Tramadol
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	Subject received tramadol tablet administered orally once daily.
Number of subjects in period 1 Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol Started 205 204 407 407 602 Completed 130 134 267 271 379 Not completed 75 70 140 136 223      Adverse event, serious fatal 2 2 1 - 1      Withdrawn Due to Pregnancy - 1 - - 1      Consent withdrawn by subject 25 20 29 48 73      Adverse event, non-fatal 3 4 4 8 18      Unspecified 21 22 58 52 76      Lost to follow-up 16 9 31 16 34      Insufficient clinical response 7 10 13 12 16      Protocol deviation 1 2 4 - 4

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Placebo Followed by Tanezumab 5 mg
Reporting group description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously (SC) once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol prolonged release (PR), orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (greater than equal to [>=] 30 percentage [%] reduction in average (low back pain intensity [LBPI]) score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 milligram (mg), SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Reporting group title	Placebo Followed by Tanezumab 10 mg
Reporting group description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 percentage % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Reporting group title	Tanezumab 5 mg
Reporting group description	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Reporting group title	Tanezumab 10 mg
Reporting group description	Tanezumab (RN624 or PF-04383119) 10 mg injection administered SC once every 8 weeks from Day 1, and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Reporting group title	Tramadol
Reporting group description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 56.
Reporting group values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol Total Number of subjects 205 204 407 407 602 1825 Age categorical Units: Subjects     In utero 0 0 0 0 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0 0 0 0 0     Newborns (0-27 days) 0 0 0 0 0 0     Infants and toddlers (28 days-23 months) 0 0 0 0 0 0     Children (2-11 years) 0 0 0 0 0 0     Adolescents (12-17 years) 0 0 0 0 0 0     Adults (18-64 years) 178 186 362 355 526 1607     From 65-84 years 27 18 45 52 76 218     85 years and over 0 0 0 0 0 0 Age Continuous Units: years     arithmetic mean (standard deviation) 49.01 ( 13.76 ) 48.97 ( 12.00 ) 48.66 ( 12.36 ) 49.15 ( 12.36 ) 48.42 ( 13.08 ) - Sex: Female, Male Units: Subjects     Female 123 113 248 218 339 1041     Male 82 91 159 189 263 784 Race/Ethnicity, Customized Units: Subjects     White 154 142 295 303 428 1322     Black or African American 35 35 65 66 102 303     Asian 13 25 39 28 65 170     Other 3 2 8 10 7 30

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Placebo Followed by Tanezumab 5 mg
Reporting group description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously (SC) once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol prolonged release (PR), orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (greater than equal to [>=] 30 percentage [%] reduction in average (low back pain intensity [LBPI]) score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 milligram (mg), SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Reporting group title	Placebo Followed by Tanezumab 10 mg
Reporting group description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 percentage % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Reporting group title	Tanezumab 5 mg
Reporting group description	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Reporting group title	Tanezumab 10 mg
Reporting group description	Tanezumab (RN624 or PF-04383119) 10 mg injection administered SC once every 8 weeks from Day 1, and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Reporting group title	Tramadol
Reporting group description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 56.
Subject analysis set title	Placebo
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 percentage % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Subject analysis set title	Tramadol PR
Subject analysis set type	Intention-to-treat
Subject analysis set description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 16.
Subject analysis set title	Placebo
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 percentage % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Subject analysis set title	Placebo
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 percentage % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Subject analysis set title	Tramadol PR
Subject analysis set type	Intention-to-treat
Subject analysis set description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 56.
Subject analysis set title	Tramadol PR
Subject analysis set type	Intention-to-treat
Subject analysis set description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 56.
Subject analysis set title	Tramadol PR
Subject analysis set type	Intention-to-treat
Subject analysis set description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 56.
Subject analysis set title	Placebo
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16.
Subject analysis set title	Tanezumab 5 mg Pooled
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily, from week 16 to week 56.Those subjects were also included who received tanezumab 5 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Subject analysis set title	Tanezumab 10 mg Pooled
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily, from week 16 to week 56.Those subjects were also included who received tanezumab 10 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Subject analysis set title	Tramadol PR
Subject analysis set type	Intention-to-treat
Subject analysis set description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 56.
Subject analysis set title	Placebo
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16.
Subject analysis set title	Tanezumab 10 mg Pooled
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily, from week 16 to week 56.Those subjects were also included who received tanezumab 10 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Subject analysis set title	Placebo
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 percentage % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily from week 16 to week 56.
Subject analysis set title	Tanezumab 5 mg Pooled
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily, from week 16 to week 56.Those subjects were also included who received tanezumab 5 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Subject analysis set title	Tanezumab 10 mg Pooled
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily, from week 16 to week 56. Those subjects were also included who received tanezumab 10 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Subject analysis set title	Pooled Placebo
Subject analysis set type	Intention-to-treat
Subject analysis set description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 16. At week 16, subjects who met efficacy responder criteria (>=30 % reduction in average LBPI score and >=15% reduction in average LBPI score relative to baseline at any week from week 1 to week 15), then received tanezumab 5 mg or 10 mg, SC, once every 8 weeks plus placebo tablets matched to tramadol PR, orally, once daily, from week 16 to week 56.

End points Top of page

Primary: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Placebo at Week 16 Top of page
End point title	Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Placebo at Week 16 [1]
End point description	Average low back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive response technology (IRT). Subjects described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. ITT population: randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).Pre-specified intent of study for efficacy data up to Week(W)16 was to analyze subjects who received placebo from Day 1 and then received tanezumab 5/10 mg at week 16, together, in placebo arm. Hence, data has been reported per four arms.
End point type	Primary
End point timeframe	Baseline, Week 16
Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale     least squares mean (standard error) -2.98 ( 0.14 ) -3.08 ( 0.14 ) -2.68 ( 0.15 ) -2.81 ( 0.12 )
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. Analysis of covariance (ANCOVA) model for imputed datasets included treatment as a fixed effect, and baseline average low back pain intensity (LBPI) as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1117
Method	ANCOVA
Parameter type	Least Square (LS) Mean Difference
Point estimate	-0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	0.07
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0281
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.4
Confidence interval
level	95%
sides	2-sided
lower limit	-0.76
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.18

Primary: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Placebo at Week 16 Top of page

Secondary: Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) at Week 16 for Tanezumab Versus (Vs) Placebo Top of page
End point title	Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) at Week 16 for Tanezumab Versus (Vs) Placebo [2]
End point description	The RMDQ is a self-administered, widely used health status measure index of how well subjects with low back pain (LBP) are able to function with regard to daily activities. It measures pain and function, using 24 items describing limitations to everyday life that can be caused by LBP. The score of the RMDQ is the total number of items checked ranging from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater disability. ITT population was analyzed. Pre-specified intent of study for efficacy data up to Week 16 was to analyze, subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm, in pooled manner. Data have been reported per four arms.
End point type	Secondary
End point timeframe	Baseline, Week 16
Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale     least squares mean (standard error) -6.27 ( 0.35 ) -6.69 ( 0.35 ) -4.95 ( 0.36 ) -5.21 ( 0.30 )
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0035
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.32
Confidence interval
level	95%
sides	2-sided
lower limit	-2.21
upper limit	-0.43
Variability estimate	Standard error of the mean
Dispersion value	0.45
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.74
Confidence interval
level	95%
sides	2-sided
lower limit	-2.64
upper limit	-0.83
Variability estimate	Standard error of the mean
Dispersion value	0.46

Secondary: Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) at Week 16 for Tanezumab Versus (Vs) Placebo Top of page

Secondary: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Tramadol at Week 16 Top of page
End point title	Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Tramadol at Week 16 [3]
End point description	Average LBP was assessed on an 11-point NRS captured through an IRT. Subjects described their average LBP during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. ITT population was analyzed. Pre-specified intent of study for efficacy data up to Week 16 was to analyze, subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm, in pooled manner. Data have been reported per four arms.
End point type	Secondary
End point timeframe	Baseline, Week 16
Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale     least squares mean (standard error) -2.98 ( 0.14 ) -3.08 ( 0.14 ) -2.68 ( 0.15 ) -2.81 ( 0.12 )
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3118
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.16
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0958
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.28
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	0.05
Variability estimate	Standard error of the mean
Dispersion value	0.17

Secondary: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Tramadol at Week 16 Top of page

Secondary: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56 Top of page
End point title	Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56 [4]
End point description	Average LBP was assessed on an 11-point NRS captured through an IRT. The LBPI score was captured once daily from baseline up to week 16, and once weekly from week 16 to week 64. Subjects described their average LBP during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Pre-specified intent of study for efficacy data up to Week 16 was to analyze, subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm, in pooled manner. Hence data have been reported per four arms. ITT population was analyzed. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to and including week 16 and comparisons of tanezumab Vs tramadol for data up to and including week 56. Hence, number analyzed is 99999 for placebo arm for week 16 and onwards.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56
Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -1.54 ( 0.09 ) -1.59 ( 0.09 ) -1.17 ( 0.09 ) -1.36 ( 0.08 )     Change at Week 4 -2.24 ( 0.12 ) -2.43 ( 0.12 ) -1.75 ( 0.12 ) -1.99 ( 0.10 )     Change at Week 8 -2.64 ( 0.13 ) -2.79 ( 0.13 ) -2.10 ( 0.13 ) -2.43 ( 0.11 )     Change at Week 12 -2.92 ( 0.13 ) -3.12 ( 0.13 ) -2.54 ( 0.13 ) -2.74 ( 0.11 )     Change at Week 24 -2.76 ( 0.16 ) -2.92 ( 0.16 ) 99999 ( 99999 ) -2.64 ( 0.14 )     Change at Week 32 -2.74 ( 0.17 ) -2.75 ( 0.16 ) 99999 ( 99999 ) -2.52 ( 0.14 )     Change at Week 40 -2.64 ( 0.17 ) -2.67 ( 0.17 ) 99999 ( 99999 ) -2.49 ( 0.14 )     Change at Week 48 -2.58 ( 0.17 ) -2.62 ( 0.17 ) 99999 ( 99999 ) -2.43 ( 0.15 )     Change at Week 56 -2.52 ( 0.17 ) -2.62 ( 0.17 ) 99999 ( 99999 ) -2.40 ( 0.15 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0015
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.37
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	-0.14
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0004
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.42
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	-0.19
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0771
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-0.41
upper limit	0.02
Variability estimate	Standard error of the mean
Dispersion value	0.11
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0959
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.39
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.11
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.037
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.44
upper limit	-0.01
Variability estimate	Standard error of the mean
Dispersion value	0.11
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0008
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.48
Confidence interval
level	95%
sides	2-sided
lower limit	-0.76
upper limit	-0.2
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.68
Confidence interval
level	95%
sides	2-sided
lower limit	-0.96
upper limit	-0.39
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0711
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.02
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0661
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.02
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0009
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.44
Confidence interval
level	95%
sides	2-sided
lower limit	-0.7
upper limit	-0.18
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0008
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.53
Confidence interval
level	95%
sides	2-sided
lower limit	-0.84
upper limit	-0.22
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.69
Confidence interval
level	95%
sides	2-sided
lower limit	-1
upper limit	-0.38
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0274
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.61
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1495
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.08
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0123
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.37
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	-0.08
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0307
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.37
Confidence interval
level	95%
sides	2-sided
lower limit	-0.71
upper limit	-0.03
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0009
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.58
Confidence interval
level	95%
sides	2-sided
lower limit	-0.91
upper limit	-0.24
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2103
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.51
upper limit	0.11
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2656
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.48
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0152
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.38
Confidence interval
level	95%
sides	2-sided
lower limit	-0.68
upper limit	-0.07
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5164
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.12
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.25
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1488
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.28
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2431
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	0.15
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2428
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.16
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4561
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.54
upper limit	0.24
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3523
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.2
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4403
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.23
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3205
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	0.19
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5763
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.11
Confidence interval
level	95%
sides	2-sided
lower limit	-0.51
upper limit	0.28
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as a fixed effect, and baseline average LBPI as a covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2887
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.61
upper limit	0.18
Variability estimate	Standard error of the mean
Dispersion value	0.2

Secondary: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56 Top of page

Secondary: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 64 Top of page
End point title	Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 64 [5]
End point description	Average LBP was assessed on an 11-point NRS captured through an IRT. The LBPI score was captured once a week for week 64. Subjects described their average LBP during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). ‘Number analyzed’ (n) = subjects evaluable for this endpoint at specified time point.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline (n= 200, 204, 406, 406, 605) 7.16 ( 1.15 ) 7.23 ( 1.09 ) 7.25 ( 1.08 ) 7.18 ( 1.13 ) 7.17 ( 1.16 )     Change at Week 64 (n= 58, 53, 126, 145, 176) -4.36 ( 2.28 ) -4.32 ( 2.01 ) -4.04 ( 2.15 ) -3.71 ( 2.39 ) -4.08 ( 2.12 )
No statistical analyses for this end point

Secondary: Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 64 Top of page

Secondary: Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Total Score at Weeks 2, 4, 8, 16 (for Tanezumab vs Tramadol) 24, 32, 40, 48 and 56 Top of page
End point title	Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Total Score at Weeks 2, 4, 8, 16 (for Tanezumab vs Tramadol) 24, 32, 40, 48 and 56 [6]
End point description	RMDQ is a self-administered, widely used health status measure index of how well subjects with LBP are able to function with regard to daily activities. It measures pain and function, using 24 items describing limitations to everyday life that can be caused by LBP. The score of the RMDQ is the total number of items checked ranging from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater disability. Pre-specified intent of study for efficacy data up to Week 16 was to analyze, subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm, in pooled manner. Hence data have been reported per four arms. ITT population was analyzed. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to and including week 16 and comparisons of tanezumab Vs tramadol for data up to and including week 56. Hence, number analyzed is 99999 for placebo arm for week 16 and onwards.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -3.30 ( 0.25 ) -3.84 ( 0.26 ) -2.46 ( 0.26 ) -2.74 ( 0.21 )     Change at Week 4 -4.58 ( 0.29 ) -5.32 ( 0.29 ) -3.37 ( 0.29 ) -3.67 ( 0.25 )     Change at Week 8 -5.27 ( 0.31 ) -5.85 ( 0.31 ) -3.90 ( 0.31 ) -4.51 ( 0.27 )     Change at Week 16 -6.27 ( 0.35 ) -6.69 ( 0.35 ) -4.95 ( 0.36 ) -5.21 ( 0.30 )     Change at Week 24 -5.57 ( 0.41 ) -5.92 ( 0.41 ) 99999 ( 99999 ) -4.59 ( 0.35 )     Change at Week 32 -5.46 ( 0.42 ) -5.71 ( 0.42 ) 99999 ( 99999 ) -4.74 ( 0.35 )     Change at Week 40 -5.12 ( 0.43 ) -5.24 ( 0.44 ) 99999 ( 99999 ) -4.53 ( 0.36 )     Change at Week 48 -4.92 ( 0.43 ) -5.14 ( 0.43 ) 99999 ( 99999 ) -4.44 ( 0.37 )     Change at Week 56 -4.85 ( 0.45 ) -5.23 ( 0.44 ) 99999 ( 99999 ) -4.41 ( 0.36 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0121
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.84
Confidence interval
level	95%
sides	2-sided
lower limit	-1.5
upper limit	-0.18
Variability estimate	Standard error of the mean
Dispersion value	0.34
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.38
Confidence interval
level	95%
sides	2-sided
lower limit	-2.05
upper limit	-0.71
Variability estimate	Standard error of the mean
Dispersion value	0.34
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3697
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.28
Confidence interval
level	95%
sides	2-sided
lower limit	-0.89
upper limit	0.33
Variability estimate	Standard error of the mean
Dispersion value	0.31
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0658
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.56
Confidence interval
level	95%
sides	2-sided
lower limit	-1.16
upper limit	0.04
Variability estimate	Standard error of the mean
Dispersion value	0.3
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0004
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.1
Confidence interval
level	95%
sides	2-sided
lower limit	-1.7
upper limit	-0.5
Variability estimate	Standard error of the mean
Dispersion value	0.31
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0013
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.22
Confidence interval
level	95%
sides	2-sided
lower limit	-1.96
upper limit	-0.48
Variability estimate	Standard error of the mean
Dispersion value	0.38
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.96
Confidence interval
level	95%
sides	2-sided
lower limit	-2.7
upper limit	-1.21
Variability estimate	Standard error of the mean
Dispersion value	0.38
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3906
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-0.99
upper limit	0.39
Variability estimate	Standard error of the mean
Dispersion value	0.35
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0082
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.92
Confidence interval
level	95%
sides	2-sided
lower limit	-1.6
upper limit	-0.24
Variability estimate	Standard error of the mean
Dispersion value	0.35
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.65
Confidence interval
level	95%
sides	2-sided
lower limit	-2.34
upper limit	-0.97
Variability estimate	Standard error of the mean
Dispersion value	0.35
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0006
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.37
Confidence interval
level	95%
sides	2-sided
lower limit	-2.15
upper limit	-0.58
Variability estimate	Standard error of the mean
Dispersion value	0.4
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.95
Confidence interval
level	95%
sides	2-sided
lower limit	-2.73
upper limit	-1.16
Variability estimate	Standard error of the mean
Dispersion value	0.4
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1004
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.61
Confidence interval
level	95%
sides	2-sided
lower limit	-1.34
upper limit	0.12
Variability estimate	Standard error of the mean
Dispersion value	0.37
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0385
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.76
Confidence interval
level	95%
sides	2-sided
lower limit	-1.47
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.37
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.34
Confidence interval
level	95%
sides	2-sided
lower limit	-2.06
upper limit	-0.61
Variability estimate	Standard error of the mean
Dispersion value	0.37
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0035
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.32
Confidence interval
level	95%
sides	2-sided
lower limit	-2.21
upper limit	-0.43
Variability estimate	Standard error of the mean
Dispersion value	0.45
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.74
Confidence interval
level	95%
sides	2-sided
lower limit	-2.64
upper limit	-0.83
Variability estimate	Standard error of the mean
Dispersion value	0.46
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5412
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-1.09
upper limit	0.57
Variability estimate	Standard error of the mean
Dispersion value	0.42
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0107
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.06
Confidence interval
level	95%
sides	2-sided
lower limit	-1.87
upper limit	-0.25
Variability estimate	Standard error of the mean
Dispersion value	0.42
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0004
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.48
Confidence interval
level	95%
sides	2-sided
lower limit	-2.29
upper limit	-0.66
Variability estimate	Standard error of the mean
Dispersion value	0.42
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0464
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.98
Confidence interval
level	95%
sides	2-sided
lower limit	-1.94
upper limit	-0.02
Variability estimate	Standard error of the mean
Dispersion value	0.49
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0068
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-1.33
Confidence interval
level	95%
sides	2-sided
lower limit	-2.3
upper limit	-0.37
Variability estimate	Standard error of the mean
Dispersion value	0.49
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1485
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.72
Confidence interval
level	95%
sides	2-sided
lower limit	-1.7
upper limit	0.26
Variability estimate	Standard error of the mean
Dispersion value	0.5
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0507
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.97
Confidence interval
level	95%
sides	2-sided
lower limit	-1.94
upper limit	0
Variability estimate	Standard error of the mean
Dispersion value	0.5
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.248
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.59
Confidence interval
level	95%
sides	2-sided
lower limit	-1.6
upper limit	0.41
Variability estimate	Standard error of the mean
Dispersion value	0.51
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1605
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.71
Confidence interval
level	95%
sides	2-sided
lower limit	-1.71
upper limit	0.28
Variability estimate	Standard error of the mean
Dispersion value	0.51
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3654
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.47
Confidence interval
level	95%
sides	2-sided
lower limit	-1.5
upper limit	0.55
Variability estimate	Standard error of the mean
Dispersion value	0.52
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1782
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.7
Confidence interval
level	95%
sides	2-sided
lower limit	-1.71
upper limit	0.32
Variability estimate	Standard error of the mean
Dispersion value	0.52
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3981
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.44
Confidence interval
level	95%
sides	2-sided
lower limit	-1.47
upper limit	0.58
Variability estimate	Standard error of the mean
Dispersion value	0.52
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline RMDQ, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1089
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.83
Confidence interval
level	95%
sides	2-sided
lower limit	-1.84
upper limit	0.18
Variability estimate	Standard error of the mean
Dispersion value	0.52

Secondary: Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Total Score at Weeks 2, 4, 8, 16 (for Tanezumab vs Tramadol) 24, 32, 40, 48 and 56 Top of page

Secondary: Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 64 and 80 Top of page
End point title	Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 64 and 80 [7]
End point description	The RMDQ is a self-administered, widely used health status measure index of how well subjects with LBP are able to function with regard to daily activities. It measures pain and function, using 24 items describing limitations to everyday life that can be caused by LBP. The score of the RMDQ is the total number of items checked ranging from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater disability. ITT population included all randomized subjects who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, “n” = subjects evaluable for this end point at specified time point.
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline (n= 202, 204, 405, 407, 605) 14.64 ( 5.26 ) 14.98 ( 5.03 ) 15.02 ( 5.21 ) 15.06 ( 4.92 ) 15.10 ( 5.11 )     Change at Week 64 (n= 63,141, 149,59,204) -8.35 ( 6.72 ) -8.71 ( 5.78 ) -8.72 ( 6.32 ) -7.64 ( 5.96 ) -8.87 ( 5.88 )     Change at Week 80 (n= 62,135, 146,59,193) -8.03 ( 7.00 ) -7.27 ( 6.79 ) -8.80 ( 6.68 ) -7.13 ( 5.99 ) -8.35 ( 6.01 )
No statistical analyses for this end point

Secondary: Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 64 and 80 Top of page

Secondary: Change from Baseline in Patient’s Global Assessment (PGA) of Low Back Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 Top of page
End point title	Change from Baseline in Patient’s Global Assessment (PGA) of Low Back Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 [8]
End point description	PGA of LBP assessed by asking question to subjects:“Considering all the ways your low back pain affects you, how are you doing today?”Subjects responded on 5 point Likert scale ranging from 1-5,by IRT,where1=very good (asymptomatic & no limitation of normal activities);2=good (mild symptoms & no limitation of normal activities);3=fair(moderate symptoms and limitation of some normal activities);4=poor (severe symptoms and inability to carry out most normal activities);5=very poor (very severe symptoms which are intolerable and inability to carry out all normal activities).Higher scores indicated worsening of condition.Pre-specified intent for efficacy data up to Week 16 was to analyze,subjects received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm.ITT.Pre-specified intent was to compare tanezumab Vs placebo for data up to & including week 16 &comparisons of tanezumab Vs tramadol for data up to & including week 56.n=99999for placebo for week 16 and above.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -0.62 ( 0.04 ) -0.67 ( 0.04 ) -0.54 ( 0.04 ) -0.54 ( 0.03 )     Change at Week 4 -0.82 ( 0.04 ) -0.86 ( 0.04 ) -0.64 ( 0.04 ) -0.66 ( 0.04 )     Change at Week 8 -0.82 ( 0.05 ) -0.89 ( 0.05 ) -0.69 ( 0.05 ) -0.76 ( 0.04 )     Change at Week 16 -0.98 ( 0.05 ) -1.02 ( 0.05 ) -0.86 ( 0.05 ) -0.85 ( 0.04 )     Change at Week 24 -0.83 ( 0.06 ) -0.82 ( 0.06 ) 99999 ( 99999 ) -0.74 ( 0.05 )     Change at Week 32 -0.80 ( 0.06 ) -0.79 ( 0.06 ) 99999 ( 99999 ) -0.74 ( 0.05 )     Change at Week 40 -0.80 ( 0.06 ) -0.75 ( 0.06 ) 99999 ( 99999 ) -0.70 ( 0.05 )     Change at Week 48 -0.74 ( 0.07 ) -0.72 ( 0.07 ) 99999 ( 99999 ) -0.66 ( 0.06 )     Change at Week 56 -0.76 ( 0.06 ) -0.74 ( 0.07 ) 99999 ( 99999 ) -0.66 ( 0.06 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1472
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-0.18
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0135
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.24
upper limit	-0.03
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.9149
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	0.01
Confidence interval
level	95%
sides	2-sided
lower limit	-0.09
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0893
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-0.18
upper limit	0.01
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0044
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.14
Confidence interval
level	95%
sides	2-sided
lower limit	-0.23
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0025
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-0.28
upper limit	-0.06
Variability estimate	Standard error of the mean
Dispersion value	0.06
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.32
upper limit	-0.1
Variability estimate	Standard error of the mean
Dispersion value	0.06
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8348
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.01
Confidence interval
level	95%
sides	2-sided
lower limit	-0.11
upper limit	0.09
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.26
upper limit	-0.06
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.3
upper limit	-0.1
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0272
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.25
upper limit	-0.01
Variability estimate	Standard error of the mean
Dispersion value	0.06
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0009
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.31
upper limit	-0.08
Variability estimate	Standard error of the mean
Dispersion value	0.06
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.168
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.18
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2968
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.06
Confidence interval
level	95%
sides	2-sided
lower limit	-0.16
upper limit	0.05
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0219
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.12
Confidence interval
level	95%
sides	2-sided
lower limit	-0.23
upper limit	-0.02
Variability estimate	Standard error of the mean
Dispersion value	0.05
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0717
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.12
Confidence interval
level	95%
sides	2-sided
lower limit	-0.25
upper limit	0.01
Variability estimate	Standard error of the mean
Dispersion value	0.07
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0207
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.29
upper limit	-0.02
Variability estimate	Standard error of the mean
Dispersion value	0.07
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8399
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	0.01
Confidence interval
level	95%
sides	2-sided
lower limit	-0.11
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.06
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0299
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.25
upper limit	-0.01
Variability estimate	Standard error of the mean
Dispersion value	0.06
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 16:Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.006
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-0.29
upper limit	-0.05
Variability estimate	Standard error of the mean
Dispersion value	0.06
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24:Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1974
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.24
upper limit	0.05
Variability estimate	Standard error of the mean
Dispersion value	0.07
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.278
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-0.22
upper limit	0.06
Variability estimate	Standard error of the mean
Dispersion value	0.07
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.433
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.06
Confidence interval
level	95%
sides	2-sided
lower limit	-0.21
upper limit	0.09
Variability estimate	Standard error of the mean
Dispersion value	0.07
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4946
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-0.2
upper limit	0.09
Variability estimate	Standard error of the mean
Dispersion value	0.07
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1884
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.1
Confidence interval
level	95%
sides	2-sided
lower limit	-0.25
upper limit	0.05
Variability estimate	Standard error of the mean
Dispersion value	0.08
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.521
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-0.2
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.08
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type
P-value	> 0.3329
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-0.23
upper limit	0.08
Variability estimate	Standard error of the mean
Dispersion value	0.08
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 48:Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5173
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.05
Confidence interval
level	95%
sides	2-sided
lower limit	-0.21
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.08
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2346
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.1
Confidence interval
level	95%
sides	2-sided
lower limit	-0.25
upper limit	0.06
Variability estimate	Standard error of the mean
Dispersion value	0.08
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline PGA, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3634
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.23
upper limit	0.09
Variability estimate	Standard error of the mean
Dispersion value	0.08

Secondary: Change from Baseline in Patient’s Global Assessment (PGA) of Low Back Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 Top of page

Secondary: Change from Baseline in Patient’s Global Assessment (PGA) of Low Back Pain at Week 64 Top of page
End point title	Change from Baseline in Patient’s Global Assessment (PGA) of Low Back Pain at Week 64 [9]
End point description	PGA of LBP was assessed by asking a question to subjects: “Considering all the ways your low back pain affects you, how are you doing today?” Subjects responded on a 5 point Likert scale ranging from 1-5, using IRT, where 1=very good (asymptomatic and no limitation of normal activities); 2=good (mild symptoms and no limitation of normal activities); 3=fair (moderate symptoms and limitation of some normal activities); 4=poor (severe symptoms and inability to carry out most normal activities); and 5=very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher scores indicated worsening of condition. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). ‘Number analyzed’ (n) = subjects evaluable for this endpoint at specified time point.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n= 202, 204, 405, 407, 605) 3.47 ( 0.65 ) 3.49 ( 0.60 ) 3.47 ( 0.61 ) 3.53 ( 0.63 ) 3.50 ( 0.63 )     Change at Week 64(n= 63, 57, 140, 147, 200) -1.21 ( 1.02 ) -1.16 ( 0.86 ) -1.03 ( 0.98 ) -1.01 ( 0.92 ) -1.14 ( 0.88 )
No statistical analyses for this end point

Secondary: Change from Baseline in Patient’s Global Assessment (PGA) of Low Back Pain at Week 64 Top of page

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline in Daily Average Low Back Pain Intensity (ALBPI) Score at Weeks 16, 24 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) Top of page
End point title	Percentage of Subjects With Cumulative Percent Change From Baseline in Daily Average Low Back Pain Intensity (ALBPI) Score at Weeks 16, 24 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) [10]
End point description	ALBP:assessed on 11-point NRS captured through an IRT.LBPI score captured once week for W64.Subjects described their average LBP during the past 24 hours on a scale ranging from 0(no pain)-10(worst possible pain),where higher scores indicated higher pain.% of subjects with cumulative reduction >0%; >=10, 20, 30, 40, 50, 60, 70, 80, 90 and=100%) in LBPI from baseline to W16, 24 and 56 were reported, subjects (%) are reported more than once in categories specified.Pre-specified intent of study for efficacy data up to W16 was to analyze,subjects who received placebo from Day 1 and received tan 5/10 mg at week 16 in placebo arm,in pooled manner.Data have been reported per 4 arms.ITT.Pre-specified intent of was to compare tan Vs placebo for data up to and including week 16 and comparisons of tan Vs tramadol for data up to and including week 56,data is 99999 for placebo arm for week 16 and onwards.“N” =subjects evaluable for this endpoint & “n”=subjects evaluable at specified time points.
End point type	Secondary
End point timeframe	Baseline, Weeks 16, 24 and 56
Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 406 406 404 605 Units: percentage of subjects number (not applicable)     Change at Week 16: >0% (n =406, 406, 404, 605) 85.3 87.2 80.8 80.8     Change at Week 16: >=10% (n =406, 406, 404, 605) 79.1 82.1 73.6 74.5     Change at Week 16: >=20% (n =406, 406, 404, 605) 72.5 73.2 64.8 64.8     Change at Week 16: >=30% (n =406, 406, 404, 605) 64.6 65.4 55.7 57.9     Change at Week 16: >=40% (n =406, 406, 404, 605) 52.1 56.3 46.8 49.9     Change at Week 16: >=50% (n =406, 406, 404, 605) 43.2 46.2 37.2 42.8     Change at Week 16: >=60% (n =406, 406, 404, 605) 33.4 36.9 29.3 32.2     Change at Week 16: >=70% (n =406, 406, 404, 605) 21.6 25.1 18.5 20.2     Change at Week 16: >=80% (n =406, 406, 404, 605) 13.3 15.7 10.3 13.4     Change at Week 16: >=90% (n =406, 406, 404, 605) 7.4 6.6 5.4 6.3     Change at Week 16: =100% (n =406, 406, 404, 605) 3.9 2.7 2.7 4.1     Change at Week 24: >0% (n =406, 406, 0, 605) 71.9 72.4 99999 66.4     Change at Week 24: >=10% (n =406, 406, 0, 605) 68.5 69.2 99999 63.1     Change at Week 24: >=20% (n =406, 406, 0, 605) 61.8 64.8 99999 58.0     Change at Week 24: >=30% (n =406, 406, 0, 605) 57.6 62.1 99999 53.6     Change at Week 24: >=40% (n =406, 406, 0, 605) 51.5 55.9 99999 47.8     Change at Week 24: >=50% (n =406, 406, 0, 605) 44.1 48.8 99999 41.2     Change at Week 24: >=60% (n =406, 406, 0, 605) 33.7 37.4 99999 32.2     Change at Week 24: >=70% (n =406, 406, 0, 605) 24.4 27.6 99999 23.8     Change at Week 24: >=80% (n =406, 406, 0, 605) 16.5 15.3 99999 14.2     Change at Week 24: >=90% (n =406, 406, 0, 605) 6.2 7.1 99999 6.6     Change at Week 24: =100% (n =406, 406, 0, 605) 3.4 5.2 99999 3.8     Change at Week 56: >0% (n =406, 406, 0, 605) 59.9 61.1 99999 58.2     Change at Week 56: >=10% (n =406, 406, 0, 605) 57.6 58.9 99999 55.7     Change at Week 56: >=20% (n =406, 406, 0, 605) 53.2 55.7 99999 51.2     Change at Week 56: >=30% (n =406, 406, 0, 605) 50.7 53.9 99999 46.8     Change at Week 56: >=40% (n =406, 406, 0, 605) 46.1 50.7 99999 42.1     Change at Week 56: >=50% (n =406, 406, 0, 605) 41.6 45.3 99999 38.7     Change at Week 56: >=60% (n =406, 406, 0, 605) 34.5 36.0 99999 31.1     Change at Week 56: >=70% (n =406, 406, 0, 605) 27.1 27.6 99999 23.3     Change at Week 56: >=80% (n =406, 406, 0, 605) 17.2 19.0 99999 15.5     Change at Week 56: >=90% (n =406, 406, 0, 605) 8.9 10.3 99999 9.3     Change at Week 56: =100% (n =406, 406, 0, 605) 6.7 7.9 99999 6.1
No statistical analyses for this end point

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline in Daily Average Low Back Pain Intensity (ALBPI) Score at Weeks 16, 24 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) Top of page

Secondary: Percentage of Subjects Achieving Average LBPI Reduction of >=30 Percent (%), >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) Top of page
End point title	Percentage of Subjects Achieving Average LBPI Reduction of >=30 Percent (%), >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) [11]
End point description	ALBP:assessed on 11-point NRS captured through IRT.LBPI score was captured once week for week 64.Subjects described their average LBP during the past 24 hours on scale ranging from 0(no pain)-10(worst possible pain),where higher scores indicated higher pain.Percentage of subjects with reduction in LBPI of at least (>=)30%, 50%, 70% and 90% at weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 & 56 compared to baseline were classified as responders to LBPI & are reported,subjects (%) are reported more than once in categories specified.Pre-specified intent of study for efficacy data up to Week 16 was to analyze, subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm,in pooled manner.Hence data have been reported per four arms.ITT.Pre-specified intent of study was to compare tanezumabVsplacebo for data up to & including week 16 & comparisons of tanezumabVstramadol for data up to & including W56. 99999=no data evaluable for placebo arm for week 16 & above.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56
Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 406 406 404 605 Units: percentage of subjects number (not applicable)     Week 2: At least 30% reduction 31.3 31.8 20.8 28.6     Week 2: At least 50% reduction 13.1 14.8 8.9 11.2     Week 2: At least 70% reduction 5.2 5.7 2.7 3.3     Week 2: At least 90% reduction 1.0 1.7 1.0 0.8     Week 4: At least 30% reduction 47.5 53.2 35.6 42.1     Week 4: At least 50% reduction 26.1 30.8 19.1 23.0     Week 4: At least 70% reduction 12.8 17.7 7.4 9.1     Week 4: At least 90% reduction 2.7 3.7 2.7 2.5     Week 8: At least 30% reduction 56.2 59.4 42.6 51.2     Week 8: At least 50% reduction 35.7 40.1 24.0 31.9     Week 8: At least 70% reduction 15.3 21.7 10.9 14.2     Week 8: At least 90% reduction 4.4 4.4 4.0 3.8     Week 12: At least 30% reduction 61.3 66.5 53.5 56.7     Week 12: At least 50% reduction 41.9 47.3 34.7 38.2     Week 12: At least 70% reduction 19.7 26.4 14.9 19.3     Week 12: At least 90% reduction 7.6 7.9 5.0 6.1     Week 16: At least 30% reduction 64.8 65.5 55.9 57.9     Week 16: At least 50% reduction 43.3 46.3 37.4 42.8     Week 16: At least 70% reduction 21.7 25.1 18.6 20.2     Week 16: At least 90% reduction 7.4 6.7 5.4 6.3     Week 24: At least 30% reduction 57.6 62.1 99999 53.6     Week 24: At least 50% reduction 44.1 48.8 99999 41.2     Week 24: At least 70% reduction 24.4 27.6 99999 23.8     Week 24: At least 90% reduction 6.2 7.1 99999 6.6     Week 32: At least 30% reduction 56.7 57.6 99999 50.6     Week 32: At least 50% reduction 44.6 46.3 99999 39.7     Week 32: At least 70% reduction 27.1 25.6 99999 22.5     Week 32: At least 90% reduction 7.6 9.6 99999 7.3     Week 40: At least 30% reduction 53.0 53.9 99999 49.4     Week 40: At least 50% reduction 43.1 44.8 99999 39.7     Week 40: At least 70% reduction 26.4 28.1 99999 24.1     Week 40: At least 90% reduction 9.6 11.3 99999 7.6     Week 48: At least 30% reduction 52.2 53.0 99999 48.6     Week 48: At least 50% reduction 43.1 44.6 99999 38.7     Week 48: At least 70% reduction 27.1 26.6 99999 23.5     Week 48: At least 90% reduction 9.4 11.1 99999 8.3     Week 56: At least 30% reduction 50.7 53.9 99999 46.8     Week 56: At least 50% reduction 41.6 45.3 99999 38.7     Week 56: At least 70% reduction 27.1 27.6 99999 23.3     Week 56: At least 90% reduction 8.9 10.3 99999 9.3
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=30%: Odds ratio (OR) and 95% Confidence interval (CI) estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0007
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.74
Confidence interval
level	95%
sides	2-sided
lower limit	1.26
upper limit	2.39
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0004
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.77
Confidence interval
level	95%
sides	2-sided
lower limit	1.29
upper limit	2.44
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0056
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.52
Confidence interval
level	95%
sides	2-sided
lower limit	1.13
upper limit	2.05
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3456
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.14
Confidence interval
level	95%
sides	2-sided
lower limit	0.87
upper limit	1.5
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2771
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.16
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.53
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0594
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.54
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	2.41
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0105
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.77
Confidence interval
level	95%
sides	2-sided
lower limit	1.14
upper limit	2.75
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.236
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.29
Confidence interval
level	95%
sides	2-sided
lower limit	0.85
upper limit	1.98
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR v Placebo
Number of subjects included in analysis	1415
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3746
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.81
upper limit	1.75
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0974
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.37
Confidence interval
level	95%
sides	2-sided
lower limit	0.94
upper limit	1.99
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0806
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.94
Confidence interval
level	95%
sides	2-sided
lower limit	0.92
upper limit	4.08
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0407
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.15
Confidence interval
level	95%
sides	2-sided
lower limit	1.03
upper limit	4.47
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5966
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.22
Confidence interval
level	95%
sides	2-sided
lower limit	0.58
upper limit	2.58
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1492
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.59
Confidence interval
level	95%
sides	2-sided
lower limit	0.85
upper limit	2.96
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.072
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.76
Confidence interval
level	95%
sides	2-sided
lower limit	0.95
upper limit	3.24
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9926
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.99
Confidence interval
level	95%
sides	2-sided
lower limit	0.25
upper limit	4
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3726
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.75
Confidence interval
level	95%
sides	2-sided
lower limit	0.51
upper limit	6.04
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7874
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.83
Confidence interval
level	95%
sides	2-sided
lower limit	0.22
upper limit	3.12
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.795
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.32
upper limit	4.46
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2065
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.1
Confidence interval
level	95%
sides	2-sided
lower limit	0.66
upper limit	6.68
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0006
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.64
Confidence interval
level	95%
sides	2-sided
lower limit	1.23
upper limit	2.17
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.05
Confidence interval
level	95%
sides	2-sided
lower limit	1.55
upper limit	2.72
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0387
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.32
Confidence interval
level	95%
sides	2-sided
lower limit	1.01
upper limit	1.71
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0903
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.24
Confidence interval
level	95%
sides	2-sided
lower limit	0.97
upper limit	1.6
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0006
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.56
Confidence interval
level	95%
sides	2-sided
lower limit	1.21
upper limit	2.01
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0166
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.5
Confidence interval
level	95%
sides	2-sided
lower limit	1.08
upper limit	2.09
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.89
Confidence interval
level	95%
sides	2-sided
lower limit	1.36
upper limit	2.62
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1389
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.27
Confidence interval
level	95%
sides	2-sided
lower limit	0.93
upper limit	1.73
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2504
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.59
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0057
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.49
Confidence interval
level	95%
sides	2-sided
lower limit	1.12
upper limit	1.98
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0126
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.83
Confidence interval
level	95%
sides	2-sided
lower limit	1.14
upper limit	2.93
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.69
Confidence interval
level	95%
sides	2-sided
lower limit	1.71
upper limit	4.22
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3485
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	0.79
upper limit	1.99
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0642
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.46
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	2.19
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.16
Confidence interval
level	95%
sides	2-sided
lower limit	1.48
upper limit	3.14
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9819
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.99
Confidence interval
level	95%
sides	2-sided
lower limit	0.42
upper limit	2.31
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4333
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.37
Confidence interval
level	95%
sides	2-sided
lower limit	0.62
upper limit	3.02
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.814
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.91
Confidence interval
level	95%
sides	2-sided
lower limit	0.41
upper limit	2
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.8331
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.09
Confidence interval
level	95%
sides	2-sided
lower limit	0.49
upper limit	2.4
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.2682
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.51
Confidence interval
level	95%
sides	2-sided
lower limit	0.73
upper limit	3.12
Statistical analysis title	Tanezumab 5 mg Vs Pooled Placebo
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.73
Confidence interval
level	95%
sides	2-sided
lower limit	1.31
upper limit	2.29
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.97
Confidence interval
level	95%
sides	2-sided
lower limit	1.49
upper limit	2.61
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0071
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.42
Confidence interval
level	95%
sides	2-sided
lower limit	1.1
upper limit	1.83
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.1187
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.22
Confidence interval
level	95%
sides	2-sided
lower limit	0.95
upper limit	1.57
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.011
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.39
Confidence interval
level	95%
sides	2-sided
lower limit	1.08
upper limit	1.79
Statistical analysis title	Tanezumab 5 mg Vs Pooled Placebo
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.76
Confidence interval
level	95%
sides	2-sided
lower limit	1.3
upper limit	2.39
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.12
Confidence interval
level	95%
sides	2-sided
lower limit	1.57
upper limit	2.87
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0069
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.48
Confidence interval
level	95%
sides	2-sided
lower limit	1.11
upper limit	1.97
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.2076
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	1.55
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0072
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.43
Confidence interval
level	95%
sides	2-sided
lower limit	1.1
upper limit	1.86
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0694
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.47
Confidence interval
level	95%
sides	2-sided
lower limit	0.97
upper limit	2.22
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.27
Confidence interval
level	95%
sides	2-sided
lower limit	1.53
upper limit	3.36
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.121
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.36
Confidence interval
level	95%
sides	2-sided
lower limit	0.92
upper limit	2
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.6706
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.08
Confidence interval
level	95%
sides	2-sided
lower limit	0.76
upper limit	1.54
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0022
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.67
Confidence interval
level	95%
sides	2-sided
lower limit	1.2
upper limit	2.32
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7546
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.12
Confidence interval
level	95%
sides	2-sided
lower limit	0.56
upper limit	2.22
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7347
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.13
Confidence interval
level	95%
sides	2-sided
lower limit	0.57
upper limit	2.24
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9029
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.96
Confidence interval
level	95%
sides	2-sided
lower limit	0.5
upper limit	1.84
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.6402
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.16
Confidence interval
level	95%
sides	2-sided
lower limit	0.62
upper limit	2.18
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.6199
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.17
Confidence interval
level	95%
sides	2-sided
lower limit	0.62
upper limit	2.2
Statistical analysis title	Tanezumab 5 mg Vs Pooled Placebo
Statistical analysis description	Week 12, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0229
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	1.05
upper limit	1.83
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 12, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0002
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.73
Confidence interval
level	95%
sides	2-sided
lower limit	1.3
upper limit	2.3
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 12, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type
P-value	> 0.315
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.14
Confidence interval
level	95%
sides	2-sided
lower limit	0.88
upper limit	1.47
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 12, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.137
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.21
Confidence interval
level	95%
sides	2-sided
lower limit	0.94
upper limit	1.57
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 12, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0018
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.52
Confidence interval
level	95%
sides	2-sided
lower limit	1.17
upper limit	1.97
Statistical analysis title	Tanezumab 5 mg Vs Pooled Placebo
Statistical analysis description	Week 12, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0342
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.36
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	1.81
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 12, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0003
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.69
Confidence interval
level	95%
sides	2-sided
lower limit	1.27
upper limit	2.24
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 12, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type
P-value	> 0.2561
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.16
Confidence interval
level	95%
sides	2-sided
lower limit	0.9
upper limit	1.51
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 12, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.2358
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.17
Confidence interval
level	95%
sides	2-sided
lower limit	0.9
upper limit	1.51
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 12, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.004
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.45
Confidence interval
level	95%
sides	2-sided
lower limit	1.13
upper limit	1.87
Statistical analysis title	Tanezumab 5 mg Vs Pooled Placebo
Statistical analysis description	Week 12, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0723
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.4
Confidence interval
level	95%
sides	2-sided
lower limit	0.97
upper limit	2.02
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 12, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.06
Confidence interval
level	95%
sides	2-sided
lower limit	1.45
upper limit	2.92
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 12, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0653
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	1.94
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 12, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.9177
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.02
Confidence interval
level	95%
sides	2-sided
lower limit	0.74
upper limit	1.4
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 12, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0088
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.49
Confidence interval
level	95%
sides	2-sided
lower limit	1.11
upper limit	2.01
Statistical analysis title	Tanezumab 5 mg Vs Pooled Placebo
Statistical analysis description	Week 12, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.1197
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.58
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	2.83
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 12, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0913
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.64
Confidence interval
level	95%
sides	2-sided
lower limit	0.92
upper limit	2.92
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 12, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type
P-value	> 0.4317
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	0.72
upper limit	2.19
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 12, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.3498
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.27
Confidence interval
level	95%
sides	2-sided
lower limit	0.77
upper limit	2.08
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 12, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.2768
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.31
Confidence interval
level	95%
sides	2-sided
lower limit	0.8
upper limit	2.15
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0101
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.45
Confidence interval
level	95%
sides	2-sided
lower limit	1.09
upper limit	1.92
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0054
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.5
Confidence interval
level	95%
sides	2-sided
lower limit	1.13
upper limit	1.99
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5493
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.08
Confidence interval
level	95%
sides	2-sided
lower limit	0.84
upper limit	1.39
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0269
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.34
Confidence interval
level	95%
sides	2-sided
lower limit	1.03
upper limit	1.74
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0144
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	1.07
upper limit	1.8
Statistical analysis title	Tanezumab 5 mg Vs Pooled Placebo
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0846
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.97
upper limit	1.7
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0101
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.45
Confidence interval
level	95%
sides	2-sided
lower limit	1.09
upper limit	1.91
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0848
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	0.97
upper limit	1.62
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.8732
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.02
Confidence interval
level	95%
sides	2-sided
lower limit	0.79
upper limit	1.32
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2734
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.15
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.48
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2839
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.21
Confidence interval
level	95%
sides	2-sided
lower limit	0.86
upper limit	1.7
Statistical analysis title	Tanezumab 10 mg Vs Pooled Placebo
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0238
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.47
Confidence interval
level	95%
sides	2-sided
lower limit	1.05
upper limit	2.07
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5212
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.11
Confidence interval
level	95%
sides	2-sided
lower limit	0.81
upper limit	1.53
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.5954
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.09
Confidence interval
level	95%
sides	2-sided
lower limit	0.8
upper limit	1.48
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0638
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.33
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	1.79
Statistical analysis title	Tanezumab 5 mg Vs Pooled Placebo
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.2661
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	0.78
upper limit	2.44
Statistical analysis title	Tanezumab 10 mg Vs pooled Placebo
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4717
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.24
Confidence interval
level	95%
sides	2-sided
lower limit	0.69
upper limit	2.21
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tramadol PR v Placebo
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type
P-value	> 0.5798
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.17
Confidence interval
level	95%
sides	2-sided
lower limit	0.68
upper limit	2
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5027
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.18
Confidence interval
level	95%
sides	2-sided
lower limit	0.72
upper limit	1.95
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.8165
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.06
Confidence interval
level	95%
sides	2-sided
lower limit	0.64
upper limit	1.77
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 24, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.1996
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.18
Confidence interval
level	95%
sides	2-sided
lower limit	0.92
upper limit	1.52
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 24, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0074
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.42
Confidence interval
level	95%
sides	2-sided
lower limit	1.1
upper limit	1.83
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 24, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3557
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.13
Confidence interval
level	95%
sides	2-sided
lower limit	0.87
upper limit	1.45
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 24, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.017
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.36
Confidence interval
level	95%
sides	2-sided
lower limit	1.06
upper limit	1.75
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 24, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8641
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.03
Confidence interval
level	95%
sides	2-sided
lower limit	0.76
upper limit	1.38
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 24, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1768
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.22
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	1.62
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 24, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7696
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.93
Confidence interval
level	95%
sides	2-sided
lower limit	0.55
upper limit	1.55
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 24, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7433
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.09
Confidence interval
level	95%
sides	2-sided
lower limit	0.66
upper limit	1.78
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 32, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0562
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.99
upper limit	1.65
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 32, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0274
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.33
Confidence interval
level	95%
sides	2-sided
lower limit	1.03
upper limit	1.71
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 32, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1206
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.22
Confidence interval
level	95%
sides	2-sided
lower limit	0.95
upper limit	1.58
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 32, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0365
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.31
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	1.69
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 32, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0964
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.96
upper limit	1.71
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 32, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2515
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.59
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 32, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8122
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.06
Confidence interval
level	95%
sides	2-sided
lower limit	0.66
upper limit	1.71
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 32, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1848
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.36
Confidence interval
level	95%
sides	2-sided
lower limit	0.86
upper limit	2.13
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 40, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2622
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.16
Confidence interval
level	95%
sides	2-sided
lower limit	0.9
upper limit	1.49
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 40, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1579
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.2
Confidence interval
level	95%
sides	2-sided
lower limit	0.93
upper limit	1.54
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 40, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2773
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.15
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.49
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 40, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1032
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.24
Confidence interval
level	95%
sides	2-sided
lower limit	0.96
upper limit	1.59
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 40, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4418
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.12
Confidence interval
level	95%
sides	2-sided
lower limit	0.84
upper limit	1.5
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 40, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1608
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.23
Confidence interval
level	95%
sides	2-sided
lower limit	0.92
upper limit	1.63
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 40, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2628
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.29
Confidence interval
level	95%
sides	2-sided
lower limit	0.83
upper limit	2.02
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 40, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0447
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.55
Confidence interval
level	95%
sides	2-sided
lower limit	1.01
upper limit	2.39
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 48, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.256
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.16
Confidence interval
level	95%
sides	2-sided
lower limit	0.9
upper limit	1.49
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 48, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.1741
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.93
upper limit	1.53
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 48, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1647
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.2
Confidence interval
level	95%
sides	2-sided
lower limit	0.93
upper limit	1.55
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 48, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0619
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.99
upper limit	1.65
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 48, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2025
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.21
Confidence interval
level	95%
sides	2-sided
lower limit	0.9
upper limit	1.61
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 48, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2601
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.18
Confidence interval
level	95%
sides	2-sided
lower limit	0.88
upper limit	1.58
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 48, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5635
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.14
Confidence interval
level	95%
sides	2-sided
lower limit	0.73
upper limit	1.77
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 48, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1338
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	2.11
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 56, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2137
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.17
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	1.51
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 56, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0256
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.33
Confidence interval
level	95%
sides	2-sided
lower limit	1.04
upper limit	1.72
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 56, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3531
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.13
Confidence interval
level	95%
sides	2-sided
lower limit	0.87
upper limit	1.46
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 56, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0358
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.31
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	1.7
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 56, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.184
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.22
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	1.62
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 56, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.125
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	0.94
upper limit	1.67
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 56, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.8266
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.95
Confidence interval
level	95%
sides	2-sided
lower limit	0.61
upper limit	1.48
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 56, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5673
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.13
Confidence interval
level	95%
sides	2-sided
lower limit	0.74
upper limit	1.72

Secondary: Percentage of Subjects Achieving Average LBPI Reduction of >=30 Percent (%), >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) Top of page

Secondary: Percentage of Subjects Achieving RMDQ Reduction of >=30%, >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) Top of page
End point title	Percentage of Subjects Achieving RMDQ Reduction of >=30%, >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) [12]
End point description	RMDQ:health status measure index of how well subjects with LBP are able to function with regard to daily activities. Measures pain and function using 24 items describing limitations to everyday life. Score of RMDQ is total number of items checked ranging from 0=no disability to 24=maximum disability, higher scores=greater disability. Percentage of subjects with reduction in LBPI of at least (>=) 30, 50, 70 and 90% at specified weeks compared to baseline were classified as responders to LBPI and are reported here. Pre-specified intent of study for efficacy data up to Week 16 was to analyze subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm. Hence, data have been reported per four arms. Comparison of tanezumab Vs placebo for data up to and including week 16 and comparisons of tanezumab Vs tramadol for data up to and including week 56 was pre-specified. Hence, number analyzed is 99999 for placebo arm for week 16 and onwards. ITT population.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 405 407 406 605 Units: percentage of subjects number (not applicable)     Week 2: At least 30% reduction 32.3 38.3 24.1 29.3     Week 2: At least 50% reduction 20.0 21.4 13.5 16.9     Week 2: At least 70% reduction 10.6 10.3 5.7 6.6     Week 2: At least 90% reduction 4.2 5.4 1.7 2.3     Week 4: At least 30% reduction 46.2 50.4 34.5 39.7     Week 4: At least 50% reduction 30.9 34.2 19.2 25.3     Week 4: At least 70% reduction 17.5 21.1 10.1 10.9     Week 4: At least 90% reduction 7.9 9.6 4.2 3.1     Week 8: At least 30% reduction 52.8 56.8 41.1 48.6     Week 8: At least 50% reduction 36.8 40.8 26.4 33.4     Week 8: At least 70% reduction 23.2 24.8 12.8 16.4     Week 8: At least 90% reduction 12.1 13.8 4.9 6.4     Week 16: At least 30% reduction 58.3 62.2 48.5 52.2     Week 16: At least 50% reduction 46.7 48.2 34.7 38.7     Week 16: At least 70% reduction 32.1 34.6 20.7 22.3     Week 16: At least 90% reduction 17.0 15.5 9.1 8.6     Week 24: At least 30% reduction 50.1 15.5 99999 44.8     Week 24: At least 50% reduction 42.5 45.0 99999 34.0     Week 24: At least 70% reduction 29.4 31.7 99999 20.7     Week 24: At least 90% reduction 16.5 18.4 99999 8.3     Week 32: At least 30% reduction 48.6 49.4 99999 43.0     Week 32: At least 50% reduction 42.0 44.7 99999 35.9     Week 32: At least 70% reduction 29.1 31.9 99999 22.5     Week 32: At least 90% reduction 17.8 17.9 99999 11.6     Week 40: At least 30% reduction 44.9 48.2 99999 41.5     Week 40: At least 50% reduction 38.5 40.8 99999 34.4     Week 40: At least 70% reduction 29.9 29.5 99999 23.3     Week 40: At least 90% reduction 17.3 17.2 99999 11.4     Week 48: At least 30% reduction 43.0 45.2 99999 40.8     Week 48: At least 50% reduction 38.0 37.8 99999 33.2     Week 48: At least 70% reduction 28.4 29.5 99999 22.0     Week 48: At least 90% reduction 16.3 17.7 99999 11.4     Week 56: At least 30% reduction 41.2 46.4 99999 41.5     Week 56: At least 50% reduction 36.5 38.8 99999 32.2     Week 56: At least 70% reduction 27.9 28.5 99999 22.3     Week 56: At least 90% reduction 17.8 18.7 99999 11.7
Statistical analysis title	Tanezumab 5 mg Vs Placebo
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0076
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.53
Confidence interval
level	95%
sides	2-sided
lower limit	1.12
upper limit	2.08
Statistical analysis title	Tanezumab 10 mg Vs Placebo
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.98
Confidence interval
level	95%
sides	2-sided
lower limit	1.46
upper limit	2.69
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.07
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.31
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	1.74
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type
P-value	> 0.2655
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.17
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.54
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Week 2, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0022
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.52
Confidence interval
level	95%
sides	2-sided
lower limit	1.16
upper limit	1.98
Statistical analysis title	Tanezumab 5 mg Vs Placebo
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0125
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.61
Confidence interval
level	95%
sides	2-sided
lower limit	1.11
upper limit	2.35
Statistical analysis title	Tanezumab 10 mg Vs Placebo
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0032
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.75
Confidence interval
level	95%
sides	2-sided
lower limit	1.21
upper limit	2.54
Statistical analysis title	Pooled Placebo Vs Tramadol PR
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.1528
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.3
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	1.85
Statistical analysis title	Tanezumab 5 mg Vs Tramadol PR
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type
P-value	> 0.1863
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.24
Confidence interval
level	95%
sides	2-sided
lower limit	0.9
upper limit	1.72
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0667
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.35
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	1.86
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0101
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2
Confidence interval
level	95%
sides	2-sided
lower limit	1.18
upper limit	3.39
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0162
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.91
Confidence interval
level	95%
sides	2-sided
lower limit	1.13
upper limit	3.25
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5599
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.17
Confidence interval
level	95%
sides	2-sided
lower limit	0.69
upper limit	1.99
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0202
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.71
Confidence interval
level	95%
sides	2-sided
lower limit	1.09
upper limit	2.68
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0335
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.64
Confidence interval
level	95%
sides	2-sided
lower limit	1.04
upper limit	2.57
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0416
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.53
Confidence interval
level	95%
sides	2-sided
lower limit	1.04
upper limit	6.17
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0075
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	3.24
Confidence interval
level	95%
sides	2-sided
lower limit	1.37
upper limit	7.69
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5374
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.33
Confidence interval
level	95%
sides	2-sided
lower limit	0.53
upper limit	3.34
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.082
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.89
Confidence interval
level	95%
sides	2-sided
lower limit	0.92
upper limit	3.89
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0108
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.43
Confidence interval
level	95%
sides	2-sided
lower limit	1.23
upper limit	4.81
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0006
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.65
Confidence interval
level	95%
sides	2-sided
lower limit	1.24
upper limit	2.2
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.95
Confidence interval
level	95%
sides	2-sided
lower limit	1.47
upper limit	2.59
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0963
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	0.96
upper limit	1.63
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0332
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.32
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	1.71
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 4, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0007
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.56
Confidence interval
level	95%
sides	2-sided
lower limit	1.21
upper limit	2.01
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.9
Confidence interval
level	95%
sides	2-sided
lower limit	1.37
upper limit	2.64
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.21
Confidence interval
level	95%
sides	2-sided
lower limit	1.6
upper limit	3.05
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0235
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.43
Confidence interval
level	95%
sides	2-sided
lower limit	1.05
upper limit	1.95
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0459
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.33
Confidence interval
level	95%
sides	2-sided
lower limit	1.01
upper limit	1.76
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 4, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.002
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.54
Confidence interval
level	95%
sides	2-sided
lower limit	1.17
upper limit	2.04
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0019
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.93
Confidence interval
level	95%
sides	2-sided
lower limit	1.27
upper limit	2.91
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.42
Confidence interval
level	95%
sides	2-sided
lower limit	1.62
upper limit	3.62
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6765
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.09
Confidence interval
level	95%
sides	2-sided
lower limit	0.72
upper limit	1.65
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0022
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.76
Confidence interval
level	95%
sides	2-sided
lower limit	1.23
upper limit	2.54
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 4, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.21
Confidence interval
level	95%
sides	2-sided
lower limit	1.56
upper limit	3.15
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.027
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.98
Confidence interval
level	95%
sides	2-sided
lower limit	1.08
upper limit	3.63
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.003
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.43
Confidence interval
level	95%
sides	2-sided
lower limit	1.35
upper limit	4.38
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.377
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.74
Confidence interval
level	95%
sides	2-sided
lower limit	0.38
upper limit	1.44
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0009
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.68
Confidence interval
level	95%
sides	2-sided
lower limit	1.49
upper limit	4.79
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 4, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	3.29
Confidence interval
level	95%
sides	2-sided
lower limit	1.87
upper limit	5.78
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0011
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.59
Confidence interval
level	95%
sides	2-sided
lower limit	1.2
upper limit	2.1
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.87
Confidence interval
level	95%
sides	2-sided
lower limit	1.41
upper limit	2.47
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0273
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.33
Confidence interval
level	95%
sides	2-sided
lower limit	1.03
upper limit	1.72
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1736
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.93
upper limit	1.54
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 8, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0092
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.4
Confidence interval
level	95%
sides	2-sided
lower limit	1.09
upper limit	1.81
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0015
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.63
Confidence interval
level	95%
sides	2-sided
lower limit	1.2
upper limit	2.2
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.95
Confidence interval
level	95%
sides	2-sided
lower limit	1.45
upper limit	2.63
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0164
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.41
Confidence interval
level	95%
sides	2-sided
lower limit	1.06
upper limit	1.86
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2857
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.16
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.51
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 8, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0149
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	1.07
upper limit	1.8
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.08
Confidence interval
level	95%
sides	2-sided
lower limit	1.43
upper limit	3.02
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.27
Confidence interval
level	95%
sides	2-sided
lower limit	1.57
upper limit	3.28
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type
P-value	> 0.118
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.34
Confidence interval
level	95%
sides	2-sided
lower limit	0.93
upper limit	1.92
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0062
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.56
Confidence interval
level	95%
sides	2-sided
lower limit	1.13
upper limit	2.14
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 8, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0009
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.7
Confidence interval
level	95%
sides	2-sided
lower limit	1.24
upper limit	2.32
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.69
Confidence interval
level	95%
sides	2-sided
lower limit	1.56
upper limit	4.61
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	3.1
Confidence interval
level	95%
sides	2-sided
lower limit	1.82
upper limit	5.28
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.312
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.33
Confidence interval
level	95%
sides	2-sided
lower limit	0.76
upper limit	2.32
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0019
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.02
Confidence interval
level	95%
sides	2-sided
lower limit	1.3
upper limit	3.14
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 8, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.33
Confidence interval
level	95%
sides	2-sided
lower limit	1.52
upper limit	3.59
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0064
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.47
Confidence interval
level	95%
sides	2-sided
lower limit	1.12
upper limit	1.95
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.74
Confidence interval
level	95%
sides	2-sided
lower limit	1.32
upper limit	2.31
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2757
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.15
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.48
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0575
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.99
upper limit	1.65
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 16, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0015
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.52
Confidence interval
level	95%
sides	2-sided
lower limit	1.17
upper limit	1.96
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0007
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.63
Confidence interval
level	95%
sides	2-sided
lower limit	1.23
upper limit	2.16
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.74
Confidence interval
level	95%
sides	2-sided
lower limit	1.31
upper limit	2.31
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2231
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.18
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	1.53
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0124
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	1.07
upper limit	1.79
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 16, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0025
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.48
Confidence interval
level	95%
sides	2-sided
lower limit	1.15
upper limit	1.91
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.82
Confidence interval
level	95%
sides	2-sided
lower limit	1.33
upper limit	2.51
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.03
Confidence interval
level	95%
sides	2-sided
lower limit	1.48
upper limit	2.79
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5701
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.09
Confidence interval
level	95%
sides	2-sided
lower limit	0.8
upper limit	1.49
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0004
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.67
Confidence interval
level	95%
sides	2-sided
lower limit	1.26
upper limit	2.22
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 16, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.86
Confidence interval
level	95%
sides	2-sided
lower limit	1.4
upper limit	2.46
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0008
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.07
Confidence interval
level	95%
sides	2-sided
lower limit	1.35
upper limit	3.17
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0059
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.84
Confidence interval
level	95%
sides	2-sided
lower limit	1.19
upper limit	2.83
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7741
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.94
Confidence interval
level	95%
sides	2-sided
lower limit	0.6
upper limit	1.46
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.21
Confidence interval
level	95%
sides	2-sided
lower limit	1.5
upper limit	3.25
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 16, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0008
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.96
Confidence interval
level	95%
sides	2-sided
lower limit	1.32
upper limit	2.9
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.089
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	0.97
upper limit	1.6
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 24, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0067
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.42
Confidence interval
level	95%
sides	2-sided
lower limit	1.1
upper limit	1.83
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0072
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.43
Confidence interval
level	95%
sides	2-sided
lower limit	1.1
upper limit	1.85
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 24, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0004
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.59
Confidence interval
level	95%
sides	2-sided
lower limit	1.23
upper limit	2.06
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0013
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.61
Confidence interval
level	95%
sides	2-sided
lower limit	1.2
upper limit	2.15
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 24, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.79
Confidence interval
level	95%
sides	2-sided
lower limit	1.34
upper limit	2.39
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.23
Confidence interval
level	95%
sides	2-sided
lower limit	1.51
upper limit	3.3
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 24, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.53
Confidence interval
level	95%
sides	2-sided
lower limit	1.72
upper limit	3.71
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 32, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0732
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.26
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	1.62
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 32, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0399
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.3
Confidence interval
level	95%
sides	2-sided
lower limit	1.01
upper limit	1.68
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 32, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0536
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.29
Confidence interval
level	95%
sides	2-sided
lower limit	1
upper limit	1.67
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 32, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0043
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.45
Confidence interval
level	95%
sides	2-sided
lower limit	1.12
upper limit	1.88
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 32, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0143
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.43
Confidence interval
level	95%
sides	2-sided
lower limit	1.07
upper limit	1.91
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 32, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0007
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.63
Confidence interval
level	95%
sides	2-sided
lower limit	1.23
upper limit	2.16
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 32, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.005
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.67
Confidence interval
level	95%
sides	2-sided
lower limit	1.17
upper limit	2.38
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 32, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0043
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.68
Confidence interval
level	95%
sides	2-sided
lower limit	1.18
upper limit	2.4
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 40, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2777
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.15
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.48
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 40, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0326
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.32
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	1.7
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 40, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1823
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.92
upper limit	1.55
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 40, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.035
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.32
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	1.71
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 40, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0164
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.42
Confidence interval
level	95%
sides	2-sided
lower limit	1.07
upper limit	1.88
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 40, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0257
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	1.04
upper limit	1.84
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 40, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.007
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.64
Confidence interval
level	95%
sides	2-sided
lower limit	1.14
upper limit	2.35
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 40, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0085
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.62
Confidence interval
level	95%
sides	2-sided
lower limit	1.13
upper limit	2.32
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 48, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4925
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.09
Confidence interval
level	95%
sides	2-sided
lower limit	0.85
upper limit	1.41
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 48, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1534
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.2
Confidence interval
level	95%
sides	2-sided
lower limit	0.93
upper limit	1.55
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 48, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1202
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.23
Confidence interval
level	95%
sides	2-sided
lower limit	0.95
upper limit	1.6
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 48, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1222
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.23
Confidence interval
level	95%
sides	2-sided
lower limit	0.95
upper limit	1.6
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 48, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0179
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.42
Confidence interval
level	95%
sides	2-sided
lower limit	1.06
upper limit	1.9
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 48, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0065
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.49
Confidence interval
level	95%
sides	2-sided
lower limit	1.12
upper limit	1.99
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 48, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0223
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.53
Confidence interval
level	95%
sides	2-sided
lower limit	1.06
upper limit	2.2
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 48, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0045
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.68
Confidence interval
level	95%
sides	2-sided
lower limit	1.17
upper limit	2.4
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 56, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9385
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.99
Confidence interval
level	95%
sides	2-sided
lower limit	0.77
upper limit	1.28
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 56, >=30%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1093
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.23
Confidence interval
level	95%
sides	2-sided
lower limit	0.95
upper limit	1.59
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 56, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1631
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.21
Confidence interval
level	95%
sides	2-sided
lower limit	0.93
upper limit	1.57
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 56, >=50%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0285
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.34
Confidence interval
level	95%
sides	2-sided
lower limit	1.03
upper limit	1.74
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 56, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0389
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.36
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	1.81
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 56, >=70%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.024
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.39
Confidence interval
level	95%
sides	2-sided
lower limit	1.04
upper limit	1.86
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 56, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0063
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.64
Confidence interval
level	95%
sides	2-sided
lower limit	1.15
upper limit	2.34
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 56, >=90%: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline RMDQ, baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0021
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.74
Confidence interval
level	95%
sides	2-sided
lower limit	1.22
upper limit	2.47

Secondary: Percentage of Subjects Achieving RMDQ Reduction of >=30%, >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF) Top of page

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 16, 24 and 56 Top of page
End point title	Percentage of Subjects With Cumulative Percent Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 16, 24 and 56 [13]
End point description	RMDQ: health status measure index of how well subjects with LBP are able to function with regard to daily activities. Measures pain and function using 24 items describing limitations to everyday life. Score of RMDQ is total number of items checked ranging from 0=no disability to 24=maximum disability, higher scores=greater disability. Percentage of subjects with reduction in LBPI of at least (>=) 30, 50, 70 and 90% at specified weeks compared to baseline were classified as responders to LBPI and are reported here. Pre-specified intent of study for efficacy data up to Week 16 was to analyze subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm. Hence, data have been reported per four arms. Comparison of tanezumab Vs placebo for data up to and including week 16 and comparisons of tanezumab Vs tramadol for data up to and including week 56 was pre-specified. Hence, number analyzed is 0 for placebo arm for week 16 and onwards. ITT population.
End point type	Secondary
End point timeframe	Baseline, Weeks 16, 24 and 56
Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 405 407 406 605 Units: percentage of subjects number (not applicable)     Change at Week 16: >=0% (n =405, 407, 406, 605) 76.8 83.5 71.2 71.2     Change at Week 16: >=10% (n =405, 407, 406, 605) 72.6 78.4 68.2 66.3     Change at Week 16: >=20% ((n =405, 407, 406, 605) 65.4 70.3 60.6 59.3     Change at Week 16: >=30% (n =405, 407, 406, 605) 58.3 62.2 48.5 52.2     Change at Week 16: >=40% (n =405, 407, 406, 605) 53.1 53.3 42.1 44.3     Change at Week 16: >=50% (n =405, 407, 406, 605) 46.7 48.2 34.7 38.7     Change at Week 16: >=60% (n =405, 407, 406, 605) 38.0 41.0 26.1 30.9     Change at Week 16: >=70% (n =405, 407, 406, 605) 32.1 34.6 20.7 22.3     Change at Week 16: >=80% (n =405, 407, 406, 605) 23.2 26.5 14.8 15.5     Change at Week 16: >=90% (n =405, 407, 406, 605) 17.0 15.5 9.1 9.1     Change at Week 16: =100% (n =405, 407, 406, 605) 13.3 9.3 6.4 4.8     Change at Week 24: >=0% (n =405, 407, 0, 605) 60.5 64.6 99999 57.7     Change at Week 24: >=10% (n =405, 407, 0, 605) 58.3 61.9 99999 55.7     Change at Week 24: >=20% (n =405, 407, 0, 605) 54.6 56.5 99999 51.1     Change at Week 24: >=30% (n =405, 407, 0, 605) 50.1 53.3 99999 44.8     Change at Week 24: >=40% (n =405, 407, 0, 605) 46.7 48.2 99999 39.5     Change at Week 24: >=50% (n =405, 407, 0, 605) 42.5 45.0 99999 34.0     Change at Week 24: >=60% (n =405, 407, 0, 605) 35.8 38.6 99999 26.1     Change at Week 24: >=70% (n =405, 407, 0, 605) 29.4 31.7 99999 20.7     Change at Week 24: >=80% (n =405, 407, 0, 605) 22.2 25.3 99999 14.2     Change at Week 24: >=90% (n =405, 407, 0, 605) 16.5 18.4 99999 8.3     Change at Week 24: =100% (n =405, 407, 0, 605) 11.6 11.5 99999 5.6     Change at Week 56: >0% (n =405, 407, 0, 605) 51.6 56.5 99999 52.6     Change at Week 56: >=10% (n =405, 407, 0, 605) 50.1 54.8 99999 49.9     Change at Week 56: >=20% (n =405, 407, 0, 605) 46.2 50.9 99999 46.0     Change at Week 56: >=30% (n =405, 407, 0, 605) 41.2 46.4 99999 41.5     Change at Week 56: >=40% (n =405, 407, 0, 605) 38.0 42.5 99999 36.2     Change at Week 56: >=50% (n =405, 407, 0, 605) 36.5 38.8 99999 32.2     Change at Week 56: >=60% (n =405, 407, 0, 605) 31.9 33.2 99999 27.1     Change at Week 56: >=70% (n =405, 407, 0, 605) 27.9 28.5 99999 22.3     Change at Week 56: >=80% (n =405, 407, 0, 605) 22.7 24.3 99999 17.2     Change at Week 56: >=90% (n =405, 407, 0, 605) 17.8 18.7 99999 11.7     Change at Week 56: =100% (n =405, 407, 0, 605) 13.8 14.0 99999 7.4
No statistical analyses for this end point

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 16, 24 and 56 Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Worst Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Worst Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data [14]
End point description	BPI-sf:questionnaire developed to assess severity of pain & pain interference on daily functions during 24 hours prior to evaluation.Severity of pain was measured based on questions 1 to 4 of pain at its ‘worst’, ‘least’, ‘average’ and ‘right now’.For Worst Pain item of BPI-sf scale(11 point NRS scale; range: 0[no pain] to 10[pain as bad as you can imagine]),subjects asked to rate their pain by marking an "X" in one of boxes that best described their pain at its worst,during 24 hours prior to evaluation,higher scores indicated greater pain severity.Question 5 (7-items) assessed level of pain interference on daily activities.Pre-specified intent for efficacy data up to Week 16 was to analyze,subjects received placebo from Day 1 and received tanezumab(tan)5/10 mg at week16 in placebo arm.Intent was to compare tan Vs placebo for data up to & including week 16 & comparisons of tan Vs tramadol for data up to &including week 56.Number analyzed=0 for placebo arm for week 16 & onwards.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -1.66 ( 0.10 ) -1.76 ( 0.10 ) -1.17 ( 0.10 ) -1.40 ( 0.09 )     Change at Week 4 -2.30 ( 0.12 ) -2.50 ( 0.12 ) -1.73 ( 0.12 ) -1.98 ( 0.11 )     Change at Week 8 -2.57 ( 0.13 ) -2.86 ( 0.13 ) -2.11 ( 0.13 ) -2.37 ( 0.11 )     Change at Week 16 -3.18 ( 0.14 ) -3.21 ( 0.14 ) -2.67 ( 0.15 ) -2.90 ( 0.12 )     Change at Week 24 -2.81 ( 0.17 ) -3.01 ( 0.17 ) 0 ( 0 ) -2.66 ( 0.14 )     Change at Week 32 -2.88 ( 0.17 ) -2.95 ( 0.17 ) 0 ( 0 ) -2.63 ( 0.15 )     Change at Week 40 -2.70 ( 0.18 ) -2.78 ( 0.18 ) 0 ( 0 ) -2.51 ( 0.15 )     Change at Week 48 -2.66 ( 0.19 ) -2.73 ( 0.18 ) 0 ( 0 ) -2.44 ( 0.15 )     Change at Week 56 -2.66 ( 0.19 ) -2.74 ( 0.18 ) 0 ( 0 ) -2.45 ( 0.15 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.49
Confidence interval
level	95%
sides	2-sided
lower limit	-0.75
upper limit	-0.22
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.59
Confidence interval
level	95%
sides	2-sided
lower limit	-0.85
upper limit	-0.33
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0615
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.47
upper limit	0.01
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0356
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	-0.02
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0032
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.36
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	-0.12
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.57
Confidence interval
level	95%
sides	2-sided
lower limit	-0.88
upper limit	-0.27
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.77
Confidence interval
level	95%
sides	2-sided
lower limit	-1.08
upper limit	-0.46
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0844
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.25
Confidence interval
level	95%
sides	2-sided
lower limit	-0.54
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0258
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0004
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.52
Confidence interval
level	95%
sides	2-sided
lower limit	-0.8
upper limit	-0.23
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0079
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.45
Confidence interval
level	95%
sides	2-sided
lower limit	-0.78
upper limit	-0.12
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.75
Confidence interval
level	95%
sides	2-sided
lower limit	-1.08
upper limit	-0.41
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0977
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.57
upper limit	0.05
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.215
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.11
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0016
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.49
Confidence interval
level	95%
sides	2-sided
lower limit	-0.79
upper limit	-0.18
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0058
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.52
Confidence interval
level	95%
sides	2-sided
lower limit	-0.88
upper limit	-0.15
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0038
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.54
Confidence interval
level	95%
sides	2-sided
lower limit	-0.91
upper limit	-0.18
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1707
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1083
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.28
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.06
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0734
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.64
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4603
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.25
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0799
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.74
upper limit	0.04
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2339
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.25
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	0.16
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1199
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.73
upper limit	0.08
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.384
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	0.23
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.27
Confidence interval
level	95%
sides	2-sided
lower limit	-0.68
upper limit	0.14
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2997
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.2
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1778
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.29
Confidence interval
level	95%
sides	2-sided
lower limit	-0.71
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3438
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.23
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1876
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.29
Confidence interval
level	95%
sides	2-sided
lower limit	-0.71
upper limit	0.14
Variability estimate	Standard error of the mean
Dispersion value	0.22

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Worst Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Worst Pain at Week 64: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Worst Pain at Week 64: Observed Data [15]
End point description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4 of pain at its ‘worst’, ‘least’, ‘average’ and ‘right now’. For the Worst Pain item of the BPI-sf scale (11 point NRS scale; range: 0 [no pain] to 10 [pain as bad as you can imagine]), subjects were asked to rate their pain by marking an "X" in one of the boxes that best described their pain at its worst, during 24 hours prior to evaluation, higher scores indicated greater pain severity. Question 5 (7-items) assessed level of pain interference on daily activities. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).”n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n=202,204,405,407,605) 7.93 ( 1.18 ) 7.91 ( 1.09 ) 7.95 ( 1.11 ) 7.92 ( 1.19 ) 7.92 ( 1.18 )     Change at Week 64(n=63,57,140,147,200) -3.90 ( 2.69 ) -4.28 ( 2.37 ) -4.01 ( 2.68 ) -3.61 ( 2.52 ) -4.23 ( 2.39 )
No statistical analyses for this end point

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Worst Pain at Week 64: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Average Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Average Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data [16]
End point description	BPI-sf: questionnaire developed to assess severity of pain & pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4 of pain at its ‘worst’, ‘least’, ‘average’ and ‘right now’. Pre-specified intent of study for efficacy data up to Week 16 was to analyze, subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm, in pooled manner. Hence data have been reported per four arms. ITT population was analyzed. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to and including week 16 and comparisons of tanezumab Vs tramadol for data up to and including week 56. Hence, number analyzed is 99999 for placebo arm for week 16 and onwards.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -1.40 ( 0.10 ) -1.47 ( 0.10 ) -0.93 ( 0.10 ) -1.20 ( 0.08 )     Change at Week 4 -2.04 ( 0.12 ) -2.22 ( 0.12 ) -1.52 ( 0.12 ) -1.76 ( 0.10 )     Change at Week 8 -2.36 ( 0.12 ) -2.60 ( 0.12 ) -1.90 ( 0.12 ) -2.20 ( 0.10 )     Change at Week 16 -2.84 ( 0.14 ) -2.93 ( 0.14 ) -2.47 ( 0.14 ) -2.64 ( 0.12 )     Change at Week 24 -2.58 ( 0.16 ) -2.72 ( 0.16 ) 99999 ( 99999 ) -2.45 ( 0.14 )     Change at Week 32 -2.61 ( 0.16 ) -2.67 ( 0.16 ) 99999 ( 99999 ) -2.43 ( 0.14 )     Change at Week 40 -2.46 ( 0.17 ) -2.53 ( 0.17 ) 99999 ( 99999 ) -2.32 ( 0.14 )     Change at Week 48 -2.40 ( 0.17 ) -2.44 ( 0.17 ) 99999 ( 99999 ) -2.29 ( 0.14 )     Change at Week 56 -2.32 ( 0.17 ) -2.51 ( 0.17 ) 99999 ( 99999 ) -2.29 ( 0.14 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.47
Confidence interval
level	95%
sides	2-sided
lower limit	-0.72
upper limit	-0.22
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.54
Confidence interval
level	95%
sides	2-sided
lower limit	-0.79
upper limit	-0.29
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0193
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.27
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0845
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.42
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0212
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.27
Confidence interval
level	95%
sides	2-sided
lower limit	-0.49
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.53
Confidence interval
level	95%
sides	2-sided
lower limit	-0.81
upper limit	-0.24
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.7
Confidence interval
level	95%
sides	2-sided
lower limit	-0.99
upper limit	-0.41
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf worst pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.079
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0336
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.29
Confidence interval
level	95%
sides	2-sided
lower limit	-0.55
upper limit	-0.02
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0008
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-0.73
upper limit	-0.19
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0034
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-0.77
upper limit	-0.15
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.7
Confidence interval
level	95%
sides	2-sided
lower limit	-1.01
upper limit	-0.39
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0361
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.59
upper limit	-0.02
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2786
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.44
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0058
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.4
Confidence interval
level	95%
sides	2-sided
lower limit	-0.68
upper limit	-0.11
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0365
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.37
Confidence interval
level	95%
sides	2-sided
lower limit	-0.71
upper limit	-0.02
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0092
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-0.8
upper limit	-0.11
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2923
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-0.49
upper limit	0.15
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2231
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.51
upper limit	0.12
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0724
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.29
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4776
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.23
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg Vs Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1482
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.27
Confidence interval
level	95%
sides	2-sided
lower limit	-0.64
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3249
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.18
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1997
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4823
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.14
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.25
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2754
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	0.17
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5861
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.11
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.29
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type
P-value	> 0.4346
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.54
upper limit	0.23
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8752
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.03
Confidence interval
level	95%
sides	2-sided
lower limit	-0.42
upper limit	0.36
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf average pain, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2663
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	0.17
Variability estimate	Standard error of the mean
Dispersion value	0.2

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Average Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Average Pain at Week 64: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Average Pain at Week 64: Observed Data [17]
End point description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4 of pain at its ‘worst’, ‘least’, ‘average’ and ‘right now’. For the Average Pain item of the BPI-sf scale (11 point NRS scale; range: 0 [no pain] to 10 [pain as bad as you can imagine]), subjects were asked to rate their pain by marking an "X" in one of the boxes that best described their pain during 24 hours prior to evaluation, higher scores indicated greater pain severity. Question 5 (7-items) assessed level of pain interference on daily activities. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).”n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n=202,204,405,407,605) 6.87 ( 1.20 ) 7.02 ( 1.15 ) 7.00 ( 1.18 ) 6.88 ( 1.21 ) 6.97 ( 1.21 )     Change at Week 64(n=63,57,140,147,200) -3.75 ( 2.37 ) -4.09 ( 1.82 ) -3.84 ( 2.23 ) -3.39 ( 2.38 ) -4.04 ( 2.06 )
No statistical analyses for this end point

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Average Pain at Week 64: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data [18]
End point description	BPI-sf:questionnaire assesses severity of pain and PI on daily functions during 24 hours prior to evaluation.Severity of pain was measured based on questions 1 to 4.Question 5(7-items) assessed level of PI on daily activities.PI index was calculated as mean of the seven BPI-sf PI items (question 5a to g),being PI with general activity;mood; walking ability;normal work (outside home and housework);relations with other people;sleep and enjoyment of life.Responses given on 11-point NRS with score ranging from 0(does not interfere) to10 (completely interferes),lower scores indicated less pain or PI.Pre-specified intent for efficacy data up to W16 was to analyze,subjects who received placebo from Day 1 and received tan 5/10 mg at w16 in placebo arm, in pooled manner.Data reported per 4 arms, intent of study was to compare tanVs placebo for data up to and including w16 and comparisons of tanVs tramadol for data up to and including w56.99999 signifies no subjects analyzed. ITT population.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -1.88 ( 0.11 ) -1.97 ( 0.11 ) -1.40 ( 0.11 ) -1.57 ( 0.10 )     Change at Week 4 -2.50 ( 0.13 ) -2.68 ( 0.13 ) -1.90 ( 0.13 ) -2.14 ( 0.11 )     Change at Week 8 -2.70 ( 0.13 ) -2.83 ( 0.13 ) -2.26 ( 0.13 ) -2.44 ( 0.11 )     Change at Week 16 -3.06 ( 0.14 ) -3.23 ( 0.14 ) -2.65 ( 0.14 ) -2.80 ( 0.12 )     Change at Week 24 -2.67 ( 0.17 ) -2.75 ( 0.16 ) 99999 ( 99999 ) -2.44 ( 0.14 )     Change at Week 32 -2.64 ( 0.16 ) -2.64 ( 0.16 ) 99999 ( 99999 ) -2.37 ( 0.14 )     Change at Week 40 -2.44 ( 0.17 ) -2.48 ( 0.17 ) 99999 ( 99999 ) -2.24 ( 0.14 )     Change at Week 48 -2.37 ( 0.17 ) -2.37 ( 0.17 ) 99999 ( 99999 ) -2.18 ( 0.14 )     Change at Week 56 -2.32 ( 0.17 ) -2.44 ( 0.17 ) 99999 ( 99999 ) -2.21 ( 0.15 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0013
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.48
Confidence interval
level	95%
sides	2-sided
lower limit	-0.77
upper limit	-0.19
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.57
Confidence interval
level	95%
sides	2-sided
lower limit	-0.87
upper limit	-0.28
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2272
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-0.43
upper limit	-0.1
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0209
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	-0.05
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0029
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.41
Confidence interval
level	95%
sides	2-sided
lower limit	-0.67
upper limit	-0.14
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.6
Confidence interval
level	95%
sides	2-sided
lower limit	-0.92
upper limit	-0.28
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.78
Confidence interval
level	95%
sides	2-sided
lower limit	-1.1
upper limit	-0.46
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1198
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.06
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.016
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.37
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	-0.07
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.55
Confidence interval
level	95%
sides	2-sided
lower limit	-0.85
upper limit	-0.25
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0091
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.44
Confidence interval
level	95%
sides	2-sided
lower limit	-0.77
upper limit	-0.11
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0007
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.57
Confidence interval
level	95%
sides	2-sided
lower limit	-0.9
upper limit	-0.24
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2264
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.48
upper limit	0.11
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0961
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.05
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0121
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.39
Confidence interval
level	95%
sides	2-sided
lower limit	-0.69
upper limit	-0.08
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.027
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.41
Confidence interval
level	95%
sides	2-sided
lower limit	-0.77
upper limit	-0.05
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0019
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.58
Confidence interval
level	95%
sides	2-sided
lower limit	-0.94
upper limit	-0.21
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3906
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.48
upper limit	0.19
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1209
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.59
upper limit	0.07
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0107
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.43
Confidence interval
level	95%
sides	2-sided
lower limit	-0.76
upper limit	-0.1
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2396
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.61
upper limit	0.15
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1088
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.69
upper limit	0.07
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1673
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.27
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.11
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1751
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.27
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	0.12
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3164
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.59
upper limit	0.19
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2253
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.15
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3408
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	0.2
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3391
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	0.2
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5818
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.11
Confidence interval
level	95%
sides	2-sided
lower limit	-0.5
upper limit	0.28
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference index, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2562
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.16
Variability estimate	Standard error of the mean
Dispersion value	0.2

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference Index at Week 64: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference Index at Week 64: Observed Data [19]
End point description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).”n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n= 202, 204, 405, 407, 605) 5.85 ( 1.90 ) 6.20 ( 1.88 ) 6.28 ( 1.81 ) 6.16 ( 1.93 ) 6.21 ( 1.88 )     Change at Week 64(n= 63, 57, 140, 147, 200) -3.87 ( 2.63 ) -4.21 ( 1.98 ) -4.00 ( 2.44 ) -3.60 ( 2.30 ) -3.98 ( 2.10 )
No statistical analyses for this end point

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference Index at Week 64: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with General Activity at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with General Activity at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data [20]
End point description	BPI-sf:questionnaire assesses severity of pain and PI on daily functions during 24 hours prior to evaluation.Severity of pain was measured based on questions 1 to 4.Question 5(7-items) assessed level of PI on daily activities.PI index was calculated as mean of the seven BPI-sf PI items (question 5a to g),being PI with general activity;mood; walking ability;normal work (outside home and housework);relations with other people;sleep and enjoyment of life.Responses given on 11-point NRS with score ranging from 0(does not interfere) to10 (completely interferes),lower scores indicated less pain or PI.Pre-specified intent for efficacy data up to W16 was to analyze,subjects who received placebo from Day 1 and received tan 5/10 mg at w16 in placebo arm, in pooled manner.Data reported per 4 arms, intent of study was to compare tanVs placebo for data up to and including w16 and comparisons of tanVs tramadol for data up to and including w56.99999 signifies no subjects analyzed. ITT population.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -1.84 ( 0.12 ) -1.91 ( 0.12 ) -1.46 ( 0.12 ) -1.53 ( 0.10 )     Change at Week 4 -2.45 ( 0.13 ) -2.71 ( 0.13 ) -1.92 ( 0.13 ) -2.14 ( 0.12 )     Change at Week 8 -2.68 ( 0.14 ) -2.86 ( 0.14 ) -2.37 ( 0.14 ) -2.54 ( 0.12 )     Change at Week 16 -3.20 ( 0.15 ) -3.35 ( 0.15 ) -2.70 ( 0.15 ) -2.89 ( 0.13 )     Change at Week 24 -2.78 ( 0.17 ) -2.87 ( 0.17 ) 99999 ( 99999 ) -2.87 ( 0.14 )     Change at Week 32 -2.74 ( 0.18 ) -2.76 ( 0.17 ) 99999 ( 99999 ) -2.52 ( 0.15 )     Change at Week 40 -2.54 ( 0.18 ) -2.58 ( 0.18 ) 99999 ( 99999 ) -2.40 ( 0.15 )     Change at Week 48 -2.47 ( 0.18 ) -2.47 ( 0.18 ) 99999 ( 99999 ) -2.33 ( 0.15 )     Change at Week 56 -2.44 ( 0.18 ) -2.53 ( 0.18 ) 99999 ( 99999 ) -2.39 ( 0.15 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0137
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.39
Confidence interval
level	95%
sides	2-sided
lower limit	-0.69
upper limit	-0.08
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0044
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.45
Confidence interval
level	95%
sides	2-sided
lower limit	-0.76
upper limit	-0.14
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.6194
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.07
Confidence interval
level	95%
sides	2-sided
lower limit	-0.35
upper limit	0.21
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0271
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.59
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0085
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.38
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	-0.1
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0027
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.53
Confidence interval
level	95%
sides	2-sided
lower limit	-0.87
upper limit	-0.18
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.78
Confidence interval
level	95%
sides	2-sided
lower limit	-1.13
upper limit	-0.44
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1859
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.54
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0573
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	0.01
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0005
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.56
Confidence interval
level	95%
sides	2-sided
lower limit	-0.88
upper limit	-0.25
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0841
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.31
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	0.04
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0074
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.49
Confidence interval
level	95%
sides	2-sided
lower limit	-0.85
upper limit	-0.13
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.316
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-0.49
upper limit	0.16
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3763
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.47
upper limit	0.18
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0505
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.32
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0118
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.49
Confidence interval
level	95%
sides	2-sided
lower limit	-0.88
upper limit	-0.11
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0012
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.64
Confidence interval
level	95%
sides	2-sided
lower limit	-1.03
upper limit	-0.25
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2966
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-0.54
upper limit	0.17
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0956
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	0.05
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0117
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.45
Confidence interval
level	95%
sides	2-sided
lower limit	-0.81
upper limit	-0.1
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3732
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.57
upper limit	0.21
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1922
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2986
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	0.19
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2584
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.17
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5195
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.14
Confidence interval
level	95%
sides	2-sided
lower limit	-0.57
upper limit	0.29
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3752
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.19
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	0.22
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5157
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.14
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.28
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5065
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.14
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.28
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8373
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.04
Confidence interval
level	95%
sides	2-sided
lower limit	-0.47
upper limit	0.38
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with general activity, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5146
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.14
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.28
Variability estimate	Standard error of the mean
Dispersion value	0.22

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with General Activity at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with General Activity at Week 64: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with General Activity at Week 64: Observed Data [21]
End point description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).”n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n=202,204,405,407,605) 6.40 ( 1.81 ) 6.69 ( 1.75 ) 6.69 ( 1.70 ) 6.66 ( 1.82 ) 6.67 ( 1.75 )     Change at Week 64(n=202,204,405,407,605) -3.87 ( 2.79 ) -4.46 ( 2.19 ) -4.03 ( 2.74 ) -3.72 ( 2.57 ) -4.16 ( 2.33 )
No statistical analyses for this end point

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with General Activity at Week 64: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Walking Ability at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Walking Ability at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data [22]
End point description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -1.72 ( 0.12 ) -1.89 ( 0.12 ) -1.28 ( 0.12 ) -1.54 ( 0.10 )     Change at Week 4 -2.38 ( 0.13 ) -2.55 ( 0.13 ) -1.81 ( 0.13 ) -2.03 ( 0.12 )     Change at Week 8 -2.60 ( 0.13 ) -2.73 ( 0.13 ) -2.17 ( 0.14 ) -2.30 ( 0.11 )     Change at Week 16 -2.90 ( 0.15 ) -3.15 ( 0.15 ) -2.55 ( 0.15 ) -2.68 ( 0.13 )     Change at Week 24 -2.54 ( 0.17 ) -2.73 ( 0.17 ) 99999 ( 99999 ) -2.30 ( 0.14 )     Change at Week 32 -2.50 ( 0.17 ) -2.59 ( 0.17 ) 99999 ( 99999 ) -2.24 ( 0.14 )     Change at Week 40 -2.31 ( 0.17 ) -2.46 ( 0.17 ) 99999 ( 99999 ) -2.09 ( 0.15 )     Change at Week 48 -2.24 ( 0.17 ) -2.34 ( 0.17 ) 99999 ( 99999 ) -2.04 ( 0.14 )     Change at Week 56 -2.24 ( 0.17 ) -2.45 ( 0.17 ) 99999 ( 99999 ) -2.07 ( 0.14 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0059
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.45
Confidence interval
level	95%
sides	2-sided
lower limit	-0.76
upper limit	-0.13
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.61
Confidence interval
level	95%
sides	2-sided
lower limit	-0.93
upper limit	-0.29
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0756
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.26
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2197
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.47
upper limit	0.11
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0208
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.34
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	-0.05
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0013
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.91
upper limit	-0.22
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.74
Confidence interval
level	95%
sides	2-sided
lower limit	-1.08
upper limit	-0.39
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1873
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0305
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	-0.03
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0013
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.52
Confidence interval
level	95%
sides	2-sided
lower limit	-0.84
upper limit	-0.2
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0158
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.43
Confidence interval
level	95%
sides	2-sided
lower limit	-0.78
upper limit	-0.08
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0015
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.56
Confidence interval
level	95%
sides	2-sided
lower limit	-0.91
upper limit	-0.21
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4173
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.45
upper limit	0.19
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0659
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.02
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0078
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.43
Confidence interval
level	95%
sides	2-sided
lower limit	-0.74
upper limit	-0.11
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0737
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.72
upper limit	0.03
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0021
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.59
Confidence interval
level	95%
sides	2-sided
lower limit	-0.97
upper limit	-0.22
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4535
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.48
upper limit	0.21
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2271
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0086
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-0.81
upper limit	-0.12
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2243
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	0.15
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0331
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.42
Confidence interval
level	95%
sides	2-sided
lower limit	-0.81
upper limit	-0.03
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1838
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.27
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0795
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.75
upper limit	0.04
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2847
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	0.18
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0745
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.36
Confidence interval
level	95%
sides	2-sided
lower limit	-0.76
upper limit	0.04
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.311
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.59
upper limit	0.19
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1375
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-0.7
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4036
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.17
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	0.23
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with walking ability, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0641
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.38
Confidence interval
level	95%
sides	2-sided
lower limit	-0.79
upper limit	0.02
Variability estimate	Standard error of the mean
Dispersion value	0.21

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Walking Ability at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Walking Ability at Week 64: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Walking Ability at Week 64: Observed Data [23]
End point description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).”n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n=202,204,405,407,605) 5.66 ( 2.28 ) 6.07 ( 2.14 ) 5.95 ( 2.22 ) 6.01 ( 2.24 ) 6.04 ( 2.03 )     Change at Week 64(n=63,57,140,147,200) -3.78 ( 2.91 ) -4.14 ( 2.37 ) -3.65 ( 2.79 ) -3.61 ( 2.65 ) -3.78 ( 2.37 )
No statistical analyses for this end point

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Walking Ability at Week 64: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Sleep at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Sleep at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data [24]
End point description	BPI-sf:questionnaire assesses severity of pain and PI on daily functions during 24 hours prior to evaluation.Severity of pain was measured based on questions 1 to 4.Question 5(7-items) assessed level of PI on daily activities.PI index was calculated as mean of the seven BPI-sf PI items (question 5a to g),being PI with general activity;mood; walking ability;normal work (outside home and housework);relations with other people;sleep and enjoyment of life.Responses given on 11-point NRS with score ranging from 0(does not interfere) to10 (completely interferes),lower scores indicated less pain or PI.Pre-specified intent for efficacy data up to W16 was to analyze,subjects who received placebo from Day 1 and received tan 5/10 mg at w16 in placebo arm, in pooled manner.Data reported per 4 arms, intent of study was to compare tanVs placebo for data up to and including w16 and comparisons of tanVs tramadol for data up to and including w56.99999 signifies no subjects analyzed. ITT population.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -2.09 ( 0.13 ) -2.15 ( 0.14 ) -1.58 ( 0.14 ) -1.80 ( 0.11 )     Change at Week 4 -2.79 ( 0.15 ) -2.98 ( 0.15 ) -2.13 ( 0.15 ) -2.34 ( 0.13 )     Change at Week 8 -2.94 ( 0.15 ) -3.13 ( 0.15 ) -2.42 ( 0.15 ) -2.70 ( 0.13 )     Change at Week 16 -3.38 ( 0.16 ) -3.44 ( 0.16 ) -2.92 ( 0.16 ) -3.00 ( 0.14 )     Change at Week 24 -2.89 ( 0.18 ) -3.09 ( 0.18 ) 99999 ( 99999 ) -2.59 ( 0.15 )     Change at Week 32 -2.88 ( 0.18 ) -2.94 ( 0.18 ) 99999 ( 99999 ) -2.54 ( 0.15 )     Change at Week 40 -2.64 ( 0.18 ) -2.81 ( 0.19 ) 99999 ( 99999 ) -2.41 ( 0.15 )     Change at Week 48 -2.61 ( 0.19 ) -2.73 ( 0.19 ) 99999 ( 99999 ) -2.34 ( 0.16 )     Change at Week 56 -2.57 ( 0.18 ) -2.74 ( 0.18 ) 99999 ( 99999 ) -2.37 ( 0.16 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0037
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.51
Confidence interval
level	95%
sides	2-sided
lower limit	-0.85
upper limit	-0.17
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0013
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.57
Confidence interval
level	95%
sides	2-sided
lower limit	-0.91
upper limit	-0.22
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1712
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.09
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0686
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.29
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	0.02
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0289
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.66
upper limit	-0.04
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.66
Confidence interval
level	95%
sides	2-sided
lower limit	-1.02
upper limit	-0.3
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.86
Confidence interval
level	95%
sides	2-sided
lower limit	-1.22
upper limit	-0.49
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2056
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.55
upper limit	0.12
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0084
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.45
Confidence interval
level	95%
sides	2-sided
lower limit	-0.78
upper limit	-0.11
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.64
Confidence interval
level	95%
sides	2-sided
lower limit	-0.98
upper limit	-0.31
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0063
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.52
Confidence interval
level	95%
sides	2-sided
lower limit	-0.9
upper limit	-0.15
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0002
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.72
Confidence interval
level	95%
sides	2-sided
lower limit	-1.09
upper limit	-0.34
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1155
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.28
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	0.07
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1652
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.59
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0129
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.44
Confidence interval
level	95%
sides	2-sided
lower limit	-0.78
upper limit	-0.09
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0236
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-0.87
upper limit	-0.06
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0136
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.52
Confidence interval
level	95%
sides	2-sided
lower limit	-0.93
upper limit	-0.11
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6624
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.09
Confidence interval
level	95%
sides	2-sided
lower limit	-0.47
upper limit	0.3
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0468
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.38
Confidence interval
level	95%
sides	2-sided
lower limit	-0.75
upper limit	-0.01
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.025
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.43
Confidence interval
level	95%
sides	2-sided
lower limit	-0.81
upper limit	-0.05
Variability estimate	Standard error of the mean
Dispersion value	0.19
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1539
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-0.72
upper limit	0.11
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0169
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.5
Confidence interval
level	95%
sides	2-sided
lower limit	-0.91
upper limit	-0.09
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1049
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.35
Confidence interval
level	95%
sides	2-sided
lower limit	-0.77
upper limit	0.07
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0599
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.4
Confidence interval
level	95%
sides	2-sided
lower limit	-0.82
upper limit	0.02
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3041
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.2
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0737
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.4
Confidence interval
level	95%
sides	2-sided
lower limit	-0.83
upper limit	0.04
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2293
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.27
Confidence interval
level	95%
sides	2-sided
lower limit	-0.71
upper limit	0.17
Variability estimate	Standard error of the mean
Dispersion value	0.23
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0806
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.39
Confidence interval
level	95%
sides	2-sided
lower limit	-0.82
upper limit	0.05
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.368
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.23
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with sleep, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0893
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.36
Confidence interval
level	95%
sides	2-sided
lower limit	-0.79
upper limit	0.06
Variability estimate	Standard error of the mean
Dispersion value	0.21

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Sleep at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Sleep at Week 64: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Sleep at Week 64: Observed Data [25]
End point description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).”n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n=202,204,405,407,605) 6.45 ( 2.49 ) 6.73 ( 2.37 ) 6.88 ( 2.31 ) 6.67 ( 2.39 ) 6.82 ( 2.38 )     Change at Week 64(n=63,57,140,147,200) -4.29 ( 3.17 ) -4.54 ( 2.80 ) -4.19 ( 2.95 ) -4.05 ( 2.70 ) -4.11 ( 2.78 )
No statistical analyses for this end point

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Sleep at Week 64: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Normal Work at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Normal Work at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data [26]
End point description	BPI-sf:questionnaire assesses severity of pain and PI on daily functions during 24 hours prior to evaluation.Severity of pain was measured based on questions 1 to 4.Question 5(7-items) assessed level of PI on daily activities.PI index was calculated as mean of the seven BPI-sf PI items (question 5a to g),being PI with general activity;mood; walking ability;normal work (outside home and housework);relations with other people;sleep and enjoyment of life.Responses given on 11-point NRS with score ranging from 0(does not interfere) to10 (completely interferes),lower scores indicated less pain or PI.Pre-specified intent for efficacy data up to W16 was to analyze,subjects who received placebo from Day 1 and received tan 5/10 mg at w16 in placebo arm, in pooled manner.Data reported per 4 arms, intent of study was to compare tanVs placebo for data up to and including w16 and comparisons of tanVs tramadol for data up to and including w56.99999 signifies no subjects analyzed. ITT population.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 2 -1.86 ( 0.12 ) -2.01 ( 0.12 ) -1.30 ( 0.12 ) -1.53 ( 0.10 )     Change at Week 4 -2.43 ( 0.14 ) -2.81 ( 0.14 ) -1.92 ( 0.14 ) -2.14 ( 0.12 )     Change at Week 8 -2.70 ( 0.14 ) -2.96 ( 0.14 ) -2.32 ( 0.14 ) -2.51 ( 0.12 )     Change at Week 16 -3.15 ( 0.15 ) -3.33 ( 0.16 ) -2.64 ( 0.15 ) -2.87 ( 0.13 )     Change at Week 24 -2.78 ( 0.17 ) -2.89 ( 0.17 ) 99999 ( 99999 ) -2.53 ( 0.15 )     Change at Week 32 -2.72 ( 0.18 ) -2.75 ( 0.18 ) 99999 ( 99999 ) -2.52 ( 0.15 )     Change at Week 40 -2.57 ( 0.18 ) -2.60 ( 0.18 ) 99999 ( 99999 ) -2.37 ( 0.15 )     Change at Week 48 -2.48 ( 0.18 ) -2.49 ( 0.18 ) 99999 ( 99999 ) -2.33 ( 0.15 )     Change at Week 56 -2.46 ( 0.18 ) -2.58 ( 0.18 ) 99999 ( 99999 ) -2.33 ( 0.16 )
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0007
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.56
Confidence interval
level	95%
sides	2-sided
lower limit	-0.88
upper limit	-0.24
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.71
Confidence interval
level	95%
sides	2-sided
lower limit	-1.03
upper limit	-0.38
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1291
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.07
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0015
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.48
Confidence interval
level	95%
sides	2-sided
lower limit	-0.77
upper limit	-0.18
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.029
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.33
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	-0.03
Variability estimate	Standard error of the mean
Dispersion value	0.15
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0041
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.52
Confidence interval
level	95%
sides	2-sided
lower limit	-0.87
upper limit	-0.17
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.89
Confidence interval
level	95%
sides	2-sided
lower limit	-1.25
upper limit	-0.54
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1799
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.55
upper limit	0.1
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0696
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.02
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.67
Confidence interval
level	95%
sides	2-sided
lower limit	-0.99
upper limit	-0.35
Variability estimate	Standard error of the mean
Dispersion value	0.16
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0387
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.38
Confidence interval
level	95%
sides	2-sided
lower limit	-0.74
upper limit	-0.02
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0005
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.64
Confidence interval
level	95%
sides	2-sided
lower limit	-1
upper limit	-0.28
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2768
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.18
Confidence interval
level	95%
sides	2-sided
lower limit	-0.51
upper limit	0.15
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2408
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.53
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0064
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-0.78
upper limit	-0.13
Variability estimate	Standard error of the mean
Dispersion value	0.17
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0115
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.51
Confidence interval
level	95%
sides	2-sided
lower limit	-0.9
upper limit	-0.11
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0006
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.69
Confidence interval
level	95%
sides	2-sided
lower limit	-1.08
upper limit	-0.29
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2028
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.59
upper limit	0.13
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1351
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.28
Confidence interval
level	95%
sides	2-sided
lower limit	-0.64
upper limit	0.09
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0133
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.46
Confidence interval
level	95%
sides	2-sided
lower limit	-0.82
upper limit	-0.09
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2157
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.25
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.15
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0781
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.36
Confidence interval
level	95%
sides	2-sided
lower limit	-0.76
upper limit	0.04
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3527
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.62
upper limit	0.22
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2994
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.2
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3326
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.21
Confidence interval
level	95%
sides	2-sided
lower limit	-0.63
upper limit	0.21
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2822
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.23
Confidence interval
level	95%
sides	2-sided
lower limit	-0.65
upper limit	0.19
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4932
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.15
Confidence interval
level	95%
sides	2-sided
lower limit	-0.57
upper limit	0.28
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4571
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.16
Confidence interval
level	95%
sides	2-sided
lower limit	-0.58
upper limit	0.26
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5586
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.13
Confidence interval
level	95%
sides	2-sided
lower limit	-0.56
upper limit	0.3
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment as fixed effects, baseline BPI-sf pain interference with normal work, and baseline average LBPI as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2664
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.24
Confidence interval
level	95%
sides	2-sided
lower limit	-0.67
upper limit	0.19
Variability estimate	Standard error of the mean
Dispersion value	0.22

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Normal Work at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data Top of page

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Normal Work at Week 64: Observed Data Top of page
End point title	Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Normal Work at Week 64: Observed Data [27]
End point description	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).”n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Week 64
Notes [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n=202,204,405,407,605) 6.31 ( 2.12 ) 6.62 ( 2.03 ) 6.65 ( 1.91 ) 6.65 ( 1.90 ) 6.56 ( 2.07 )     Change at Week 64(n=63,57,140,147,200) -3.95 ( 2.99 ) -4.60 ( 2.46 ) -4.15 ( 2.86 ) -3.80 ( 2.71 ) -4.08 ( 2.39 )
No statistical analyses for this end point

Secondary: Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Pain Interference with Normal Work at Week 64: Observed Data Top of page

Secondary: Number of Subjects who Responded for Chronic Low Back Pain Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 Top of page
End point title	Number of Subjects who Responded for Chronic Low Back Pain Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 [28]
End point description	Chronic LBP responder index analysis:composite endpoint of aLBPI score, PGA of LBP, RMDQ total score. Subjects were successful responders if they had: >=30 percent reduction in mean daily average LBPI from baseline to particular week; decrease of >=30 percent in PGA of low back pain from baseline to particular week or no worsening (increase) in RMDQ total score from baseline to particular week. Pre-specified intent of study for efficacy data up to W16 was to analyze, subjects who received placebo from Day 1 and received tan 5/10 mg at week 16 in placebo arm, in pooled manner. Data have been reported per four arms. ITT population. Pre-specified intent of study was to compare tan Vs placebo for data up to and including week 16 and comparisons of tan Vs tramadol for data up to and including week 56.Number analyzed is 99999 for placebo arm for week 16 and onwards. Here ‘Number of Subjects Analyzed (N)” = subjects who were evaluable for this endpoint.
End point type	Secondary
End point timeframe	Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Placebo Number of subjects analysed 404 406 605 404 Units: count of subjects     Week 2 62 76 74 32     Week 4 115 130 134 67     Week 8 131 151 178 86     Week 16 168 179 211 136     Week 24 166 158 207 99999     Week 32 158 160 204 99999     Week 40 158 149 202 99999     Week 48 148 140 197 99999     Week 56 140 144 192 99999
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	808
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.14
Confidence interval
level	95%
sides	2-sided
lower limit	1.36
upper limit	3.36
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.68
Confidence interval
level	95%
sides	2-sided
lower limit	1.73
upper limit	4.16
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.03
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.62
Confidence interval
level	95%
sides	2-sided
lower limit	1.05
upper limit	2.51
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	808
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.03
Confidence interval
level	95%
sides	2-sided
lower limit	1.44
upper limit	2.86
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.37
Confidence interval
level	95%
sides	2-sided
lower limit	1.69
upper limit	3.32
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.029
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.44
Confidence interval
level	95%
sides	2-sided
lower limit	1.04
upper limit	1.99
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	808
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0003
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.8
Confidence interval
level	95%
sides	2-sided
lower limit	1.31
upper limit	2.47
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type	superiority
P-value	< 0.0001
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	2.21
Confidence interval
level	95%
sides	2-sided
lower limit	1.62
upper limit	3.03
Statistical analysis title	Placebo Versus Tramadol PR
Statistical analysis description	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0033
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.56
Confidence interval
level	95%
sides	2-sided
lower limit	1.16
upper limit	2.1
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	808
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0179
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.41
Confidence interval
level	95%
sides	2-sided
lower limit	1.06
upper limit	1.88
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	810
Analysis specification	Pre-specified
Analysis type
P-value	> 0.0021
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.56
Confidence interval
level	95%
sides	2-sided
lower limit	1.18
upper limit	2.08
Statistical analysis title	Placebo Versus Tramadol PR
Statistical analysis description	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6629
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.06
Confidence interval
level	95%
sides	2-sided
lower limit	0.81
upper limit	1.38
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0251
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.35
Confidence interval
level	95%
sides	2-sided
lower limit	1.04
upper limit	1.75
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 24: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1278
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.22
Confidence interval
level	95%
sides	2-sided
lower limit	0.94
upper limit	1.59
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 32: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0749
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.27
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	1.65
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 32: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0633
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.99
upper limit	1.66
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 40: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0626
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.99
upper limit	1.67
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 40: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2727
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.16
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.51
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 48: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1749
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.2
Confidence interval
level	95%
sides	2-sided
lower limit	0.92
upper limit	1.57
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 48: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5239
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.09
Confidence interval
level	95%
sides	2-sided
lower limit	0.84
upper limit	1.42
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 56: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1009
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3336
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.14
Confidence interval
level	95%
sides	2-sided
lower limit	0.87
upper limit	1.49
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 56: OR and 95% CI estimated from logistic regression model. Logistic regression model included treatment as fixed effect and baseline average LBPI, baseline PGA, and baseline RMDQ as covariates.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2163
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.18
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	1.54

Secondary: Number of Subjects who Responded for Chronic Low Back Pain Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 Top of page

Secondary: Percentage of Subjects Achieving Improvement of >=2 Points in Patient’s Global Assessment (PGA) of Low Back Pain From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56:Mixed Baseline Observation Carried Forward (BOCF)/ Last Observation CF (LOCF) Top of page
End point title	Percentage of Subjects Achieving Improvement of >=2 Points in Patient’s Global Assessment (PGA) of Low Back Pain From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56:Mixed Baseline Observation Carried Forward (BOCF)/ Last Observation CF (LOCF) [29]
End point description	PGA of LBP assessed by asking a question to subjects: “Considering all the ways your low back pain affects you, how are you doing today?” Subjects responded on a 5 point Likert scale ranging from 1-5, using IRT, Higher scores indicated worsening of condition. Percentage of subjects with improvement of at least 2 points from baseline in PGA of LBP were reported. Missing data was imputed using mixed BOCF/LOCF. Pre-specified intent for efficacy data up to W16 was to analyze, subjects who received placebo from Day 1 and received tan 5/10 mg at w16 in placebo arm, in pooled manner. Data reported per 4 arms, intent of study was to compare tan Vs placebo for data up to and including w16 and comparisons of tan Vs tramadol for data up to and including w56.99999 signifies no subjects analyzed. ITT population. Here,”N”=subjects evaluable for this endpoint.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Notes [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 405 407 406 605 Units: percentage of subjects number (not applicable)     Week 2 11.1 14.7 9.4 10.1     Week 4 20.5 21.4 13.8 15.0     Week 8 20.2 24.1 15.3 18.8     Week 16 27.4 30.0 22.7 22.5     Week 24 25.9 25.1 99999 21.5     Week 32 25.2 23.1 99999 20.7     Week 40 25.9 25.1 99999 20.7     Week 48 23.2 22.4 99999 20.5     Week 56 24.2 21.1 99999 20.5
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.326
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.28
Confidence interval
level	95%
sides	2-sided
lower limit	0.78
upper limit	2.08
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0445
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.61
Confidence interval
level	95%
sides	2-sided
lower limit	1.01
upper limit	2.56
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9263
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.02
Confidence interval
level	95%
sides	2-sided
lower limit	0.65
upper limit	1.61
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3194
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	0.81
upper limit	1.94
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0308
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.58
Confidence interval
level	95%
sides	2-sided
lower limit	1.04
upper limit	2.38
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0048
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.79
Confidence interval
level	95%
sides	2-sided
lower limit	1.2
upper limit	2.69
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0114
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.68
Confidence interval
level	95%
sides	2-sided
lower limit	1.12
upper limit	2.51
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7857
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.06
Confidence interval
level	95%
sides	2-sided
lower limit	0.71
upper limit	1.56
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0041
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.7
Confidence interval
level	95%
sides	2-sided
lower limit	1.18
upper limit	2.44
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0109
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.59
Confidence interval
level	95%
sides	2-sided
lower limit	1.11
upper limit	2.28
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0363
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.53
Confidence interval
level	95%
sides	2-sided
lower limit	1.03
upper limit	2.27
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.004
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.76
Confidence interval
level	95%
sides	2-sided
lower limit	1.2
upper limit	2.59
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1992
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.27
Confidence interval
level	95%
sides	2-sided
lower limit	0.88
upper limit	1.84
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3084
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.2
Confidence interval
level	95%
sides	2-sided
lower limit	0.85
upper limit	1.7
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0586
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.38
Confidence interval
level	95%
sides	2-sided
lower limit	0.99
upper limit	1.94
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	811
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.063
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.39
Confidence interval
level	95%
sides	2-sided
lower limit	0.98
upper limit	1.97
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0347
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.45
Confidence interval
level	95%
sides	2-sided
lower limit	1.03
upper limit	2.04
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.79
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.96
Confidence interval
level	95%
sides	2-sided
lower limit	0.69
upper limit	1.33
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0207
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.45
Confidence interval
level	95%
sides	2-sided
lower limit	1.06
upper limit	2
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0093
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.51
Confidence interval
level	95%
sides	2-sided
lower limit	1.11
upper limit	2.07
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 24: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.04
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.39
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	1.91
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 24: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2478
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.21
Confidence interval
level	95%
sides	2-sided
lower limit	0.88
upper limit	1.65
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 32: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0304
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.24
Confidence interval
level	95%
sides	2-sided
lower limit	1.03
upper limit	1.96
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 32: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4763
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.12
Confidence interval
level	95%
sides	2-sided
lower limit	0.81
upper limit	1.56
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 40: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0178
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.47
Confidence interval
level	95%
sides	2-sided
lower limit	1.07
upper limit	2.01
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 40: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5223
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.11
Confidence interval
level	95%
sides	2-sided
lower limit	0.8
upper limit	1.53
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 48: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1708
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.25
Confidence interval
level	95%
sides	2-sided
lower limit	0.91
upper limit	1.72
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 48: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6022
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.09
Confidence interval
level	95%
sides	2-sided
lower limit	0.79
upper limit	1.5
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 56: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1010
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0846
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.32
Confidence interval
level	95%
sides	2-sided
lower limit	0.96
upper limit	1.81
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 56: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of low back pain, baseline average LBPI, and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9626
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.01
Confidence interval
level	95%
sides	2-sided
lower limit	0.73
upper limit	1.39

Secondary: Percentage of Subjects Achieving Improvement of >=2 Points in Patient’s Global Assessment (PGA) of Low Back Pain From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56:Mixed Baseline Observation Carried Forward (BOCF)/ Last Observation CF (LOCF) Top of page

Secondary: European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Top of page
End point title	European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score [30]
End point description	EQ-5D-5L:standardized subjects completed questionnaire that measures health-related quality of life (QOL) and translates that score into an index value or utility score.EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS).EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Individual dimension scores ranged from 1.0 (least impairment of health state) to 5.0 (most impairment of health state).Each dimension has 5 levels:1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Health utility score for a subject with no problems in all 5 items is 1 for all countries (except for Zimbabwe where it is 0.9), and is reduced where a subject reports greater levels of problems across the five dimensions. ITT population was analyzed and “n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Weeks 8, 16, 24, 40 and 56
Notes [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline:Mobility(n=202,204,405,407,605) 2.5 ( 0.84 ) 2.6 ( 0.88 ) 2.5 ( 0.83 ) 2.6 ( 0.82 ) 2.6 ( 0.86 )     Baseline:Self-care(n=202,204,405,407,605) 2.0 ( 0.95 ) 2.1 ( 0.97 ) 2.0 ( 0.95 ) 2.0 ( 0.92 ) 2.0 ( 0.95 )     Baseline:Usual activities(n=202,204,405,407,605) 2.8 ( 0.90 ) 2.8 ( 0.83 ) 2.8 ( 0.82 ) 2.8 ( 0.80 ) 2.8 ( 0.84 )     Baseline:Pain/Discomfort(n=202,204,405,407,605) 3.3 ( 0.73 ) 3.4 ( 0.71 ) 3.4 ( 0.68 ) 3.3 ( 0.69 ) 3.3 ( 0.70 )     Baseline:Anxiety/Depression(n=202,204,405,407,605) 1.8 ( 0.99 ) 1.9 ( 1.03 ) 1.9 ( 1.01 ) 1.9 ( 0.98 ) 1.9 ( 1.00 )     Week 8: Mobility(n=183,184,374,375,557) 1.9 ( 0.78 ) 2.0 ( 0.90 ) 1.8 ( 0.85 ) 1.8 ( 0.81 ) 1.9 ( 0.87 )     Week 8: Selfcare(n=183,184,374,375,557) 1.5 ( 0.71 ) 1.7 ( 0.79 ) 1.4 ( 0.66 ) 1.4 ( 0.65 ) 1.5 ( 0.73 )     Week8:Usual activities(n=183,184,374,375,557) 2.2 ( 0.81 ) 2.2 ( 0.89 ) 2.0 ( 0.85 ) 2.0 ( 0.82 ) 2.1 ( 0.91 )     Week8:Pain/Discomfort(n=183,184,374,375,557) 2.7 ( 0.82 ) 2.6 ( 0.84 ) 2.5 ( 0.80 ) 2.4 ( 0.80 ) 2.5 ( 0.79 )     Week8:Anxiety/Depression(n=183,184,374,375,557) 1.5 ( 0.81 ) 1.6 ( 0.92 ) 1.5 ( 0.83 ) 1.5 ( 0.78 ) 1.6 ( 0.84 )     Week16: Mobility(n=161,163,333,338,452) 1.7 ( 0.82 ) 1.8 ( 0.85 ) 1.7 ( 0.78 ) 1.6 ( 0.75 ) 1.8 ( 0.79 )     Week16:Self-care(n=161,163,333,338,452) 1.4 ( 0.64 ) 1.5 ( 0.72 ) 1.3 ( 0.62 ) 1.3 ( 0.61 ) 1.5 ( 0.69 )     Week16: Usual activities(n=161,163,333,338,452) 1.9 ( 0.81 ) 2.0 ( 0.85 ) 1.8 ( 0.84 ) 1.8 ( 0.80 ) 1.9 ( 0.82 )     Week16: Pain/Discomfort(n=161,163,333,338,452) 2.3 ( 0.90 ) 2.4 ( 0.86 ) 2.2 ( 0.83 ) 2.2 ( 0.75 ) 2.3 ( 0.76 )     Week16: Anxiety/Depression(n=161,163,333,338,452) 1.4 ( 0.68 ) 1.5 ( 0.82 ) 1.5 ( 0.83 ) 1.4 ( 0.77 ) 1.5 ( 0.79 )     Week24: Mobility(n=86, 88,222,227,285) 1.5 ( 0.63 ) 1.6 ( 0.79 ) 1.6 ( 0.75 ) 1.5 ( 0.66 ) 1.7 ( 0.75 )     Week24: Selfcare(n=86, 88,222,227,285) 1.3 ( 0.47 ) 1.4 ( 0.75 ) 1.3 ( 0.58 ) 1.2 ( 0.51 ) 1.3 ( 0.59 )     Week24: Usual activities(n=86, 88,222,227,285) 1.6 ( 0.68 ) 1.7 ( 0.71 ) 1.6 ( 0.71 ) 1.7 ( 0.67 ) 1.7 ( 0.72 )     Week24: Pain/Discomfort(n=86, 88,222,227,285) 2.0 ( 0.64 ) 1.9 ( 0.70 ) 2.1 ( 0.76 ) 2.0 ( 0.74 ) 2.1 ( 0.75 )     Week24: Anxiety/Depression(n=86,88,222,227,285) 1.2 ( 0.44 ) 1.3 ( 0.64 ) 1.4 ( 0.73 ) 1.3 ( 0.65 ) 1.3 ( 0.66 )     Week40: Mobility(n=70, 73,162,174,225) 1.5 ( 0.76 ) 1.5 ( 0.62 ) 1.5 ( 0.75 ) 1.5 ( 0.70 ) 1.6 ( 0.73 )     Week40: Selfcare(n=70, 73,162,174,225) 1.2 ( 0.62 ) 1.3 ( 0.53 ) 1.2 ( 0.46 ) 1.2 ( 0.45 ) 1.3 ( 0.62 )     Week 40:Usualactivities(n=70, 73,162,174,225) 1.6 ( 0.69 ) 1.6 ( 0.73 ) 1.6 ( 0.72 ) 1.7 ( 0.68 ) 1.7 ( 0.76 )     Week 40:Pain/Discomfort(n=70,73,162,174,225) 1.9 ( 0.62 ) 1.9 ( 0.64 ) 2.0 ( 0.73 ) 1.9 ( 0.75 ) 2.0 ( 0.72 )     Week40: Anxiety/Depression(n=70,73,162,174,225) 1.2 ( 0.49 ) 1.3 ( 0.60 ) 1.3 ( 0.64 ) 1.3 ( 0.68 ) 1.4 ( 0.63 )     Week56: Mobility(n=62, 62,134,154,197) 1.4 ( 0.61 ) 1.5 ( 0.72 ) 1.5 ( 0.69 ) 1.4 ( 0.67 ) 1.6 ( 0.83 )     Week 56: Self-care(n=62,62,134,154,197) 1.1 ( 0.44 ) 1.3 ( 0.52 ) 1.2 ( 0.55 ) 1.2 ( 0.43 ) 1.4 ( 0.66 )     Week 56:Usualactivities(n=62, 62,134,154,197) 1.6 ( 0.82 ) 1.6 ( 0.69 ) 1.6 ( 0.78 ) 1.6 ( 0.73 ) 1.7 ( 0.82 )     Week 56:Pain/Discomfort(n=62,62,134,154,197) 2.0 ( 0.77 ) 1.9 ( 0.66 ) 2.0 ( 0.72 ) 1.9 ( 0.72 ) 2.0 ( 0.74 )     Week 56:Anxiety/Depression(n=62,62,134,154,197) 1.3 ( 0.54 ) 1.3 ( 0.55 ) 1.4 ( 0.77 ) 1.3 ( 0.70 ) 1.3 ( 0.63 )
No statistical analyses for this end point

Secondary: European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Top of page

Secondary: European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value Top of page
End point title	European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value [31]
End point description	EQ-5D-5L: standardized subject completed questionnaire that measures health-related QOL and translates that score into an index value or utility score.EQ-5D-5L consists of 2 components: a health state profile and an optional VAS.EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Individual dimension scores ranged from 1.0 to 5.0. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Responses from five domains were used to calculate a single utility index (Overall health utility score) where values are <= 1.Overall health utility score for a subject with no problems in all 5 items is 1 for all countries (except for Zimbabwe where it is 0.9), and reduced where subject reports greater levels of problems across five dimensions. ITT population and “n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline, Weeks 8, 16, 24, 40 and 56
Notes [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: units on a scale arithmetic mean (standard deviation)     Baseline(n=202,204,405,407,605) 0.62 ( 0.16 ) 0.61 ( 0.15 ) 0.61 ( 0.16 ) 0.62 ( 0.16 ) 0.61 ( 0.16 )     Week 8(n=183,184,374,375,557) 0.74 ( 0.13 ) 0.71 ( 0.14 ) 0.75 ( 0.13 ) 0.76 ( 0.14 ) 0.74 ( 0.14 )     Week 16(n=161,163,333,338,452) 0.77 ( 0.14 ) 0.75 ( 0.14 ) 0.78 ( 0.14 ) 0.79 ( 0.13 ) 0.77 ( 0.13 )     Week 24(n=86, 88,222,227,285) 0.82 ( 0.10 ) 0.81 ( 0.13 ) 0.80 ( 0.13 ) 0.82 ( 0.12 ) 0.80 ( 0.12 )     Week 40(n=70, 73, 162,174,225) 0.83 ( 0.11 ) 0.82 ( 0.12 ) 0.82 ( 0.12 ) 0.83 ( 0.12 ) 0.80 ( 0.14 )     Week 56(n=62, 62,134,154,197) 0.85 ( 0.11 ) 0.82 ( 0.13 ) 0.82 ( 0.14 ) 0.84 ( 0.12 ) 0.81 ( 0.14 )
No statistical analyses for this end point

Secondary: European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value Top of page

Secondary: Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Baseline: Observed Data Top of page
End point title	Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Baseline: Observed Data [32]
End point description	WPAI: LBP is 6-question subject rated questionnaire that measures the effect of subject’s chronic low back pain (CLBP) on general health and symptom severity on work productivity and regular activities. It yields 4 sub-scores: work time missed due to pain (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.Pre-specified intent for efficacy data up to W16 was to analyze, subjects who received placebo from Day 1 and received tan 5/10 mg at w16 in placebo arm, in pooled manner. Data reported per 4 arms. ITT population was analyzed and “n”= subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Baseline
Notes [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale arithmetic mean (standard deviation)     Percent Work TimeMissed(n=236,236,232,316) 11.1 ( 21.03 ) 10.8 ( 19.89 ) 8.2 ( 17.43 ) 10.7 ( 20.12 )     PercentImpairment WhileWorking(n=230,232,229,313) 60.8 ( 19.68 ) 60.6 ( 20.56 ) 57.9 ( 21.25 ) 61.2 ( 19.83 )     Percent Overall WorkImpairment(n=230,232,229, 313) 63.2 ( 20.34 ) 63.1 ( 21.69 ) 60.2 ( 22.11 ) 63.6 ( 20.93 )     Percent Activity Impairment(n=405,407,406,605) 66.6 ( 17.57 ) 65.1 ( 18.33 ) 65.7 ( 18.13 ) 65.4 ( 18.31 )
No statistical analyses for this end point

Secondary: Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Baseline: Observed Data Top of page

Secondary: Change from Baseline in Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Weeks 16, 56 and 64 Top of page
End point title	Change from Baseline in Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Weeks 16, 56 and 64 [33]
End point description	WPAI:LBP:6-question subject rated questionnaire that measures effect of subject’s chronic LBP on general health and symptom severity on work productivity and regular activities. It yields 4 sub-scores: work time missed due to pain (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. ITT population was analyzed. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to and including week (W) 16 and comparisons of tanezumab Vs tramadol for data up to & including week 56. Hence, "n" is 0 for placebo arm for week 16 and onwards.“n”= subjects evaluable for this endpoint for specified categories.'99999' = signifies that no subjects were evaluable, hence mean and standard deviation not applicable.Change at Week: CAW.
End point type	Secondary
End point timeframe	Baseline, Weeks 16, 56 and 64
Notes [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Change at Week 16:Absenteeism (n=179,174,171,208) -5.07 ( 1.15 ) -5.89 ( 1.16 ) -5.82 ( 1.18 ) -5.68 ( 1.07 )     CAW16:%Impairment While Working(n=173,170,166,204) -29.49 ( 1.71 ) -30.22 ( 1.72 ) -25.46 ( 1.75 ) -27.11 ( 1.58 )     CAW16:%Overall Work Impairment(n=173,170,166,204) -30.49 ( 1.75 ) -31.95 ( 1.77 ) -26.54 ( 1.80 ) -28.29 ( 1.62 )     CAW16:%Activity Impairment(n=337,343,329,457) -32.25 ( 1.38 ) -32.25 ( 1.38 ) -28.07 ( 1.39 ) -30.83 ( 1.23 )     CAW56:%Work Time Missed (n=77,77,0,87) -8.06 ( 1.11 ) -7.48 ( 1.11 ) 99999 ( 99999 ) -7.19 ( 1.05 )     CAW56:%Impairment While Working(n=76,76,0,87) -39.38 ( 2.03 ) -41.32 ( 2.02 ) 99999 ( 99999 ) -38.51 ( 1.89 )     CAW56:%Overall Work Impairment(n=76,76,0,87) -41.18 ( 2.18 ) -42.63 ( 2.18 ) 99999 ( 99999 ) -39.25 ( 2.04 )     CAW56:%Activity Impairment(n=134,154,0,197) -43.53 ( 1.75 ) -44.16 ( 1.63 ) 99999 ( 99999 ) -43.00 ( 1.47 )
Statistical analysis title	Pooled Placebo versus Tanezumab 5 mg
Statistical analysis description	Change at Week 16: Percent Work Time Missed: ANCOVA model included treatment as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6508
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	0.74
Confidence interval
level	95%
sides	2-sided
lower limit	-2.49
upper limit	3.98
Variability estimate	Standard error of the mean
Dispersion value	1.64
Statistical analysis title	Pooled Placebo versus Tanezumab 10 mg
Statistical analysis description	Change at Week 16: Percent Work Time Missed: ANCOVA model included treatment as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9629
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.08
Confidence interval
level	95%
sides	2-sided
lower limit	-3.33
upper limit	3.18
Variability estimate	Standard error of the mean
Dispersion value	1.66
Statistical analysis title	Pooled Placebo versus Tramadol PR
Statistical analysis description	Change at Week 16: Percent Work Time Missed: ANCOVA model included treatment as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9295
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	0.14
Confidence interval
level	95%
sides	2-sided
lower limit	-2.99
upper limit	3.27
Variability estimate	Standard error of the mean
Dispersion value	1.59
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Change at Week 16: Percent Work Time Missed: ANCOVA model included treatment as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7007
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	0.6
Confidence interval
level	95%
sides	2-sided
lower limit	-2.48
upper limit	3.69
Variability estimate	Standard error of the mean
Dispersion value	1.57
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 16: Percent Work Time Missed: ANCOVA model included treatment as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8902
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.22
Confidence interval
level	95%
sides	2-sided
lower limit	-3.32
upper limit	2.88
Variability estimate	Standard error of the mean
Dispersion value	1.58
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Change at Week 56: Percent Work Time Missed: ANCOVA model included treatment as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5698
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.87
Confidence interval
level	95%
sides	2-sided
lower limit	-3.89
upper limit	2.15
Variability estimate	Standard error of the mean
Dispersion value	1.53
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Change at Week 56: Percent Work Time Missed: ANCOVA model included treatment as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8464
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	-0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-3.32
upper limit	2.72
Variability estimate	Standard error of the mean
Dispersion value	1.53

Secondary: Change from Baseline in Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Weeks 16, 56 and 64 Top of page

Secondary: Number of Subjects Who Withdrew Due to Lack of Efficacy Top of page
End point title	Number of Subjects Who Withdrew Due to Lack of Efficacy [34]
End point description	Number of subjects who withdrew from treatment due to lack of efficacy have been reported here. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).
End point type	Secondary
End point timeframe	Baseline up to Week 56
Notes [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: subjects 25 41 41 46 65
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7366
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.93
Confidence interval
level	95%
sides	2-sided
lower limit	0.62
upper limit	1.41
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline average LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.771
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.06
Confidence interval
level	95%
sides	2-sided
lower limit	0.71
upper limit	1.58

Secondary: Number of Subjects Who Withdrew Due to Lack of Efficacy Top of page

Secondary: Time to Discontinuation Due to Lack of Efficacy Top of page
End point title	Time to Discontinuation Due to Lack of Efficacy [35]
End point description	Time to discontinuation due to lack of efficacy was defined as the time interval from the date of first study drug administration up to the date of discontinuation of subject from treatment due to lack of efficacy. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, “N” signifies subjects who discontinued from the study due to lack of efficacy. Here, 100 signifies that due to the Kaplan-Meier estimate not reaching the level for discontinuation due to insufficient clinical response, lack of efficacy, median could not be calculated.
End point type	Secondary
End point timeframe	Baseline up to Week 56
Notes [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: days     median (full range (min-max)) 100 (14 to 123) 100 (8 to 122) 100 (14 to 252) 100 (2 to 175) 100 (2 to 314)
Statistical analysis title	Tanezumab 10 mg Versus Tramadol
Statistical analysis description	Missing data for the selected percentile(s) was due to the Kaplan-Meier estimate not reaching the level for discontinuation due to lack of efficacy.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7142
Method	Logrank
Confidence interval
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Missing data for the selected percentile(s) was due to the Kaplan-Meier estimate not reaching the level for discontinuation due to lack of efficacy.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4724
Method	Logrank
Confidence interval

Secondary: Time to Discontinuation Due to Lack of Efficacy Top of page

Secondary: Number of Subjects Who Took Rescue Medication During Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64 Top of page
End point title	Number of Subjects Who Took Rescue Medication During Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64 [36]
End point description	In case of inadequate pain relief, acetaminophen/paracetamol caplets, tablets, or capsules up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between day 1 and week 56. Number of subjects with any use of rescue medication during the particular study week were summarized. For analyses after week 16 where multiple imputation was used, data was reported per 3 arms. This is because subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16, received placebo for the first 16 weeks, and their data before week 16 were not be imputed into analyses after week 16. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here,” Number of Subjects Analyzed (N)”=subjects evaluable for this end point and “number analysed (n)” subjects evaluable for this endpoint at specified time points.
End point type	Secondary
End point timeframe	Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64
Notes [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 407 407 604 Units: subjects     Week 2(n=406,406,402) 226 208 318     Week 4(n=407,407,604) 205 175 285     Week (n=407,407,604) 176 158 250     Week 12(n=407,407,604) 150 147 216     Week 16(n=407,407,604) 134 125 193     Week 24(n=407,407,604) 145 150 211     Week 32(n=407,407,604) 146 152 210     Week 40(n=407,407,604) 145 144 209     Week 48(n=407,407,604) 141 144 210     Week 56(n=407,407,604) 142 142 215
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.396
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.12
Confidence interval
level	95%
sides	2-sided
lower limit	0.87
upper limit	1.44
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 2: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5932
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.93
Confidence interval
level	95%
sides	2-sided
lower limit	0.73
upper limit	1.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3326
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.13
Confidence interval
level	95%
sides	2-sided
lower limit	0.88
upper limit	1.46
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 4: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1765
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.84
Confidence interval
level	95%
sides	2-sided
lower limit	0.65
upper limit	1.08
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5619
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.08
Confidence interval
level	95%
sides	2-sided
lower limit	0.84
upper limit	1.39
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 8: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3909
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.89
Confidence interval
level	95%
sides	2-sided
lower limit	0.69
upper limit	1.16
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 12: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7562
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.04
Confidence interval
level	95%
sides	2-sided
lower limit	0.8
upper limit	1.35
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 12: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9476
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.01
Confidence interval
level	95%
sides	2-sided
lower limit	0.78
upper limit	1.31
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7746
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.04
Confidence interval
level	95%
sides	2-sided
lower limit	0.79
upper limit	1.36
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 16: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6377
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.94
Confidence interval
level	95%
sides	2-sided
lower limit	0.71
upper limit	1.23
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8532
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.03
Confidence interval
level	95%
sides	2-sided
lower limit	0.79
upper limit	1.33
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 24: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5644
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.08
Confidence interval
level	95%
sides	2-sided
lower limit	0.83
upper limit	1.4
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 32: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.769
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.04
Confidence interval
level	0.77%
sides	2-sided
lower limit	0.8
upper limit	1.35
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 32: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4321
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.11
Confidence interval
level	95%
sides	2-sided
lower limit	0.85
upper limit	1.44
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 40: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7714
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.04
Confidence interval
level	95%
sides	2-sided
lower limit	0.8
upper limit	1.35
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 40: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8389
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.03
Confidence interval
level	95%
sides	2-sided
lower limit	0.79
upper limit	1.34
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 48: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9383
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.99
Confidence interval
level	95%
sides	2-sided
lower limit	0.76
upper limit	1.29
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 48: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.88
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	1.02
Confidence interval
level	95%
sides	2-sided
lower limit	0.78
upper limit	1.33
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 56: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7946
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.97
Confidence interval
level	95%
sides	2-sided
lower limit	0.74
upper limit	1.26
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 56: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline LBPI and treatment.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7803
Method	Regression, Logistic
Parameter type	Odds ratio (OR)
Point estimate	0.96
Confidence interval
level	95%
sides	2-sided
lower limit	0.74
upper limit	1.25

Secondary: Number of Subjects Who Took Rescue Medication During Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64 Top of page

Secondary: Number of Subjects Who Took Rescue Medication During Week 64: Observed Data Top of page
End point title	Number of Subjects Who Took Rescue Medication During Week 64: Observed Data [37]
End point description	In case of inadequate pain relief, after Week 24, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of subjects with any use of rescue medication during the 4 weeks up to and including the particular study week were summarized. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, ‘N’ signifies subjects who were evaluable for this endpoint.
End point type	Secondary
End point timeframe	Week 64
Notes [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Number of subjects analysed 61 60 Units: subjects 35 26
No statistical analyses for this end point

Secondary: Number of Subjects Who Took Rescue Medication During Week 64: Observed Data Top of page

Secondary: Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56 Top of page
End point title	Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56 [38]
End point description	In case of inadequate pain relief, acetaminophen/paracetamol caplets, tablets, or capsules up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between day 1 and week 56. Number of days the subjects used the rescue medication during the particular study weeks were summarized. For analyses after week 16 where multiple imputation was used, data was reported per 3 arms. This is because subjects who received placebo from Day 1 and received tanezumab 5/10 mg at week 16, received placebo for the first 16 weeks, and their data before week 16 were not be imputed into analyses after week 16. ITT population included all randomized subjects who received at least one dose of SC study medication (either tanezumab or matching placebo).
End point type	Secondary
End point timeframe	Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56
Notes [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 407 407 605 Units: days least squares mean (standard error)     Week 2 2.05 ( 0.15 ) 1.85 ( 0.14 ) 1.76 ( 0.11 )     Week 4 1.62 ( 0.13 ) 1.40 ( 0.12 ) 1.46 ( 0.10 )     Week 8 1.40 ( 0.13 ) 1.15 ( 0.11 ) 1.23 ( 0.09 )     Week 12 1.25 ( 0.13 ) 1.02 ( 0.11 ) 1.11 ( 0.09 )     Week 16 1.18 ( 0.13 ) 0.96 ( 0.11 ) 0.99 ( 0.09 )     Week 24 1.36 ( 0.15 ) 1.35 ( 0.14 ) 1.32 ( 0.12 )     Week 32 1.35 ( 0.15 ) 1.36 ( 0.15 ) 1.38 ( 0.12 )     Week 40 1.39 ( 0.15 ) 1.24 ( 0.14 ) 1.37 ( 0.12 )     Week 48 1.32 ( 0.14 ) 1.25 ( 0.14 ) 1.37 ( 0.12 )     Week 56 1.32 ( 0.14 ) 1.22 ( 0.13 ) 1.42 ( 0.12 )
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1272
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.16
Confidence interval
level	95%
sides	2-sided
lower limit	0.96
upper limit	1.41
Variability estimate	Standard error of the mean
Dispersion value	0.11
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 2: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6322
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.05
Confidence interval
level	95%
sides	2-sided
lower limit	0.86
upper limit	1.27
Variability estimate	Standard error of the mean
Dispersion value	0.1
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3559
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.1
Confidence interval
level	95%
sides	2-sided
lower limit	0.89
upper limit	1.36
Variability estimate	Standard error of the mean
Dispersion value	0.12
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 4: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6798
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.96
Confidence interval
level	95%
sides	2-sided
lower limit	0.77
upper limit	1.18
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.267
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.14
Confidence interval
level	95%
sides	2-sided
lower limit	0.9
upper limit	1.44
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 8: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5865
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.94
Confidence interval
level	95%
sides	2-sided
lower limit	0.74
upper limit	1.19
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 12: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3378
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.13
Confidence interval
level	95%
sides	2-sided
lower limit	0.88
upper limit	1.47
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 12: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.551
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.92
Confidence interval
level	95%
sides	2-sided
lower limit	0.71
upper limit	1.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2088
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.2
Confidence interval
level	95%
sides	2-sided
lower limit	0.9
upper limit	1.6
Variability estimate	Standard error of the mean
Dispersion value	0.18
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 16: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8692
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.98
Confidence interval
level	95%
sides	2-sided
lower limit	0.73
upper limit	1.3
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 24: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8444
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.03
Confidence interval
level	95%
sides	2-sided
lower limit	0.78
upper limit	1.35
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 24: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8936
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.02
Confidence interval
level	95%
sides	2-sided
lower limit	0.78
upper limit	1.34
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 32: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8716
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.98
Confidence interval
level	95%
sides	2-sided
lower limit	0.75
upper limit	1.28
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 32: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8827
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.98
Confidence interval
level	95%
sides	2-sided
lower limit	0.75
upper limit	1.29
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 40: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8996
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.02
Confidence interval
level	95%
sides	2-sided
lower limit	0.77
upper limit	1.34
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 40: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.488
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.91
Confidence interval
level	95%
sides	2-sided
lower limit	0.69
upper limit	1.2
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Tanezumab 5 mg versus Tramadol PR
Statistical analysis description	Week 48: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7938
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.96
Confidence interval
level	95%
sides	2-sided
lower limit	0.73
upper limit	1.27
Variability estimate	Standard error of the mean
Dispersion value	0.14
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 48: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5092
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.91
Confidence interval
level	95%
sides	2-sided
lower limit	0.69
upper limit	1.2
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Tanezumab 5 mg VersusTramadol PR
Statistical analysis description	Week 56: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6148
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.93
Confidence interval
level	95%
sides	2-sided
lower limit	0.71
upper limit	1.22
Variability estimate	Standard error of the mean
Dispersion value	0.13
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 56: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2844
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.86
Confidence interval
level	95%
sides	2-sided
lower limit	0.66
upper limit	1.13
Variability estimate	Standard error of the mean
Dispersion value	0.12

Secondary: Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56 Top of page

Secondary: Number of Days of Rescue Medication Used at Week 64 Top of page
End point title	Number of Days of Rescue Medication Used at Week 64 [39]
End point description	In case of inadequate pain relief, acetaminophen/paracetamol caplets, tablets, or capsules up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between day 1 and week 56. Number of days per week the subjects used the rescue medication during the 4 weeks up to and including the particular study week were summarized. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, ‘N’ signifies subjects who were evaluable for this endpoint.
End point type	Secondary
End point timeframe	Week 64
Notes [39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 61 60 136 151 193 Units: days     arithmetic mean (standard deviation) 1.3 ( 1.59 ) 1.3 ( 2.02 ) 1.3 ( 1.99 ) 1.4 ( 2.16 ) 1.8 ( 2.44 )
No statistical analyses for this end point

Secondary: Number of Days of Rescue Medication Used at Week 64 Top of page

Secondary: Amount of Rescue Medication Used at Weeks 2, 4, 8, 12 and 16 Top of page
End point title	Amount of Rescue Medication Used at Weeks 2, 4, 8, 12 and 16 [40]
End point description	In case of inadequate pain relief, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication. The total dosage of acetaminophen in milligrams used during the specified week were summarized. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).
End point type	Secondary
End point timeframe	Weeks 2, 4, 8, 12 and 16
Notes [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: milligrams least squares mean (standard error)     Week 2 2663.2 ( 431.26 ) 2465.7 ( 398.76 ) 2420.1 ( 392.67 ) 2340.4 ( 310.28 )     Week 4 1967.2 ( 352.25 ) 1847.9 ( 330.64 ) 2084.6 ( 374.33 ) 1852.2 ( 271.70 )     Week 8 1682.3 ( 338.34 ) 1612.5 ( 323.86 ) 1757.9 ( 354.02 ) 1512.4 ( 248.85 )     Week 12 1491.6 ( 330.87 ) 1345.3 ( 297.82 ) 1707.2 ( 379.30 ) 1464.2 ( 265.85 )     Week 16 1537.8 ( 377.76 ) 1359.0 ( 333.62 ) 1385.0 ( 340.93 ) 1296.8 ( 260.75 )
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 2: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6764
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.1
Confidence interval
level	95%
sides	2-sided
lower limit	0.7
upper limit	1.73
Variability estimate	Standard error of the mean
Dispersion value	0.25
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 2: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9351
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.02
Confidence interval
level	95%
sides	2-sided
lower limit	0.65
upper limit	1.6
Variability estimate	Standard error of the mean
Dispersion value	0.23
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 2: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8731
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.97
Confidence interval
level	95%
sides	2-sided
lower limit	0.64
upper limit	1.46
Variability estimate	Standard error of the mean
Dispersion value	0.2
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 2: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.537
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.14
Confidence interval
level	95%
sides	2-sided
lower limit	0.75
upper limit	1.72
Variability estimate	Standard error of the mean
Dispersion value	0.24
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 2: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8031
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.05
Confidence interval
level	95%
sides	2-sided
lower limit	0.7
upper limit	1.59
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 4: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8192
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.94
Confidence interval
level	95%
sides	2-sided
lower limit	0.57
upper limit	1.55
Variability estimate	Standard error of the mean
Dispersion value	0.24
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	Week 4: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6345
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.89
Confidence interval
level	95%
sides	2-sided
lower limit	0.54
upper limit	1.46
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 4: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6103
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.89
Confidence interval
level	95%
sides	2-sided
lower limit	0.56
upper limit	1.4
Variability estimate	Standard error of the mean
Dispersion value	0.21
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 4: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7949
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.06
Confidence interval
level	95%
sides	2-sided
lower limit	0.67
upper limit	1.67
Variability estimate	Standard error of the mean
Dispersion value	0.25
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 4: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.992
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1
Confidence interval
level	95%
sides	2-sided
lower limit	0.63
upper limit	1.57
Variability estimate	Standard error of the mean
Dispersion value	0.23
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 8: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8772
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.96
Confidence interval
level	95%
sides	2-sided
lower limit	0.55
upper limit	1.67
Variability estimate	Standard error of the mean
Dispersion value	0.27
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 8: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7614
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.92
Confidence interval
level	95%
sides	2-sided
lower limit	0.53
upper limit	1.6
Variability estimate	Standard error of the mean
Dispersion value	0.26
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 8: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5629
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.86
Confidence interval
level	95%
sides	2-sided
lower limit	0.52
upper limit	1.43
Variability estimate	Standard error of the mean
Dispersion value	0.22
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 8: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6821
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.11
Confidence interval
level	95%
sides	2-sided
lower limit	0.67
upper limit	1.85
Variability estimate	Standard error of the mean
Dispersion value	0.29
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 8: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8049
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.07
Confidence interval
level	95%
sides	2-sided
lower limit	0.64
upper limit	1.77
Variability estimate	Standard error of the mean
Dispersion value	0.28
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 12: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6673
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.87
Confidence interval
level	95%
sides	2-sided
lower limit	0.47
upper limit	1.62
Variability estimate	Standard error of the mean
Dispersion value	0.27
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 12: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4475
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.79
Confidence interval
level	95%
sides	2-sided
lower limit	0.43
upper limit	1.46
Variability estimate	Standard error of the mean
Dispersion value	0.25
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 12: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5925
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.86
Confidence interval
level	95%
sides	2-sided
lower limit	0.49
upper limit	1.5
Variability estimate	Standard error of the mean
Dispersion value	0.25
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 12: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9486
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.02
Confidence interval
level	95%
sides	2-sided
lower limit	0.58
upper limit	1.79
Variability estimate	Standard error of the mean
Dispersion value	0.29
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	Week 12: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7673
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.92
Confidence interval
level	95%
sides	2-sided
lower limit	0.52
upper limit	1.61
Variability estimate	Standard error of the mean
Dispersion value	0.26
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	Week 16: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.7635
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.11
Confidence interval
level	95%
sides	2-sided
lower limit	0.56
upper limit	2.2
Variability estimate	Standard error of the mean
Dispersion value	0.39
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	Week 16: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.9564
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.98
Confidence interval
level	95%
sides	2-sided
lower limit	0.5
upper limit	1.94
Variability estimate	Standard error of the mean
Dispersion value	0.34
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	Week 16: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8359
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	0.94
Confidence interval
level	95%
sides	2-sided
lower limit	0.5
upper limit	1.75
Variability estimate	Standard error of the mean
Dispersion value	0.3
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	Week 16: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5914
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.19
Confidence interval
level	95%
sides	2-sided
lower limit	0.64
upper limit	2.21
Variability estimate	Standard error of the mean
Dispersion value	0.38
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	Week 16: Analysis was performed using negative binomial model with model terms of Baseline average LBPI and treatment group.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8826
Method	Negative binomial model
Parameter type	LS Mean Ratio
Point estimate	1.05
Confidence interval
level	95%
sides	2-sided
lower limit	0.56
upper limit	1.95
Variability estimate	Standard error of the mean
Dispersion value	0.33

Secondary: Amount of Rescue Medication Used at Weeks 2, 4, 8, 12 and 16 Top of page

Secondary: Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain Top of page
End point title	Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain [41]
End point description	Low back pain HCRU assessed utilization of healthcare resources usage during last 3 months (for Baseline during the last 3 months for baseline, weeks 64 and 80, via IRT). Visits of services directly related to low back pain evaluated were: visits to primary care physician, neurologist, rheumatologist, physician assistant or nurse practitioner, pain specialist, orthopedist, physical therapist, chiropractor, alternative medicine or therapy, podiatrist, nutritionist/dietitian, radiologist, home healthcare services and other practitioner. Subjects might have been counted more than once under various categories.ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, “n” subjects evaluable for OM at specified time points.
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: visits median (full range (min-max))     Baseline: Primary Care Physician 1.0 (1.0 to 8.0) 2.0 (1.0 to 114.0) 2.0 (1.0 to 111.0) 2.0 (1.0 to 14.0) 2.0 (1.0 to 562.0)     Baseline: Neurologist 1.0 (1.0 to 2.0) 1.0 (1.0 to 3.0) 1.0 (1.0 to 2.0) 1.0 (1.0 to 6.0) 1.0 (1.0 to 4.0)     Baseline: Rheumatologist 2.0 (1.0 to 2.0) 1.0 (1.0 to 3.0) 2.0 (1.0 to 5.0) 1.0 (1.0 to 3.0) 1.0 (1.0 to 6.0)     Baseline:Physician assistant or nurse Practitioner 1.0 (1.0 to 6.0) 2.0 (1.0 to 10.0) 1.0 (1.0 to 5.0) 1.0 (1.0 to 6.0) 1.0 (1.0 to 6.0)     Baseline: Pain specialist 2.0 (1.0 to 22.0) 2.0 (1.0 to 25.0) 2.0 (1.0 to 30.0) 2.0 (1.0 to 222.0) 2.0 (1.0 to 11.0)     Baseline: Orthopedist 3.0 (1.0 to 8.0) 3.0 (1.0 to 36.0) 3.0 (1.0 to 15.0) 2.0 (1.0 to 12.0) 3.0 (1.0 to 16.0)     Baseline: Physical therapist 6.5 (1.0 to 24.0) 8.0 (1.0 to 36.0) 4.5 (1.0 to 20.0) 5.5 (1.0 to 111.0) 3.5 (1.0 to 90.0)     Baseline: Chiropractor 3.0 (1.0 to 10.0) 3.0 (1.0 to 36.0) 3.5 (1.0 to 30.0) 3.0 (1.0 to 24.0) 3.0 (1.0 to 121.0)     Baseline: Alternative medicine or therapy 2.0 (1.0 to 10.0) 2.0 (1.0 to 121.0) 3.0 (1.0 to 111.0) 2.0 (1.0 to 45.0) 2.0 (1.0 to 211.0)     Baseline: Podiatrist 2.0 (1.0 to 3.0) 99999 (99999 to 99999) 2.0 (1.0 to 3.0) 1.0 (1.0 to 2.0) 1.0 (1.0 to 1.0)     Baseline: Nutritionist/dietitian 99999 (99999 to 99999) 3.0 (1.0 to 100.0) 1.5 (1.0 to 6.0) 2.0 (1.0 to 4.0) 1.0 (1.0 to 1.0)     Baseline: Radiologist 1.0 (1.0 to 3.0) 1.5 (1.0 to 3.0) 1.0 (1.0 to 6.0) 1.0 (1.0 to 10.0) 1.0 (1.0 to 4.0)     Baseline: Home healthcare services 7.5 (3.0 to 12.0) 6.0 (1.0 to 11.0) 99999 (99999 to 99999) 1.0 (1.0 to 3.0) 6.5 (1.0 to 36.0)     Baseline: Other practitioner 1.0 (1.0 to 6.0) 2.0 (1.0 to 90.0) 1.0 (1.0 to 8.0) 2.0 (1.0 to 111.0) 1.0 (1.0 to 36.0)     Week 64: Primary Care Physician 1.0 (1.0 to 5.0) 1.0 (1.0 to 299.0) 1.0 (1.0 to 211.0) 1.0 (1.0 to 201.0) 1.0 (1.0 to 200.0)     Week 64: Neurologist 1.0 (1.0 to 18.0) 1.5 (1.0 to 3.0) 1.0 (1.0 to 4.0) 1.5 (1.0 to 3.0) 1.0 (1.0 to 101.0)     Week 64: Rheumatologist 2.0 (1.0 to 14.0) 1.0 (1.0 to 27.0) 1.0 (1.0 to 100.0) 1.0 (1.0 to 101.0) 1.0 (1.0 to 2.0)     Week 64: Physician assistant or nurse Practitioner 1.0 (1.0 to 201.0) 1.0 (1.0 to 8.0) 2.0 (1.0 to 6.0) 1.0 (1.0 to 3.0) 1.0 (1.0 to 3.0)     Week 64: Pain specialist 1.0 (1.0 to 16.0) 2.0 (1.0 to 100.0) 2.0 (1.0 to 10.0) 1.0 (1.0 to 201.0) 1.0 (1.0 to 4.0)     Week 64: Orthopedist 2.0 (1.0 to 9.0) 1.5 (1.0 to 27.0) 1.0 (1.0 to 6.0) 1.0 (1.0 to 201.0) 2.0 (1.0 to 100.0)     Week 64: Physical therapist 10.0 (1.0 to 18.0) 8.0 (1.0 to 36.0) 4.5 (1.0 to 20.0) 4.0 (1.0 to 30.0) 3.0 (1.0 to 999.0)     Week 64: Chiropractor 6.0 (1.0 to 36.0) 2.5 (1.0 to 100.0) 2.0 (1.0 to 25.0) 3.5 (1.0 to 92.0) 2.0 (1.0 to 999.0)     Week 64: Alternative medicine or therapy 6.0 (1.0 to 300.0) 1.0 (1.0 to 2.0) 2.0 (1.0 to 24.0) 1.0 (1.0 to 5.0) 1.0 (1.0 to 111.0)     Week 64: Podiatrist 1.5 (1.0 to 2.0) 2.0 (1.0 to 3.0) 1.0 (1.0 to 2.0) 1.0 (1.0 to 2.0) 1.0 (1.0 to 1.0)     Week 64: Nutritionist/dietitian 99999 (99999 to 99999) 1.0 (1.0 to 100.0) 1.0 (1.0 to 1.0) 1.0 (1.0 to 1.0) 1.0 (1.0 to 9.0)     Week 64: Radiologist 1.0 (1.0 to 3.0) 1.5 (1.0 to 3.0) 1.0 (1.0 to 2.0) 1.0 (1.0 to 1.0) 1.0 (1.0 to 2.0)     Week 64: Home healthcare services 8.0 (8.0 to 8.0) 3.0 (1.0 to 5.0) 1.0 (1.0 to 1.0) 2.0 (1.0 to 3.0) 16.5 (1.0 to 401.0)     Week 64: Other practitioner 1.0 (1.0 to 18.0) 2.0 (1.0 to 100.0) 1.0 (1.0 to 111.0) 1.0 (1.0 to 16.0) 1.0 (1.0 to 6.0)     Week 80: Primary Care Physician 2.0 (1.0 to 3.0) 1.0 (1.0 to 36.0) 1.0 (1.0 to 101.0) 1.0 (1.0 to 4.0) 1.0 (1.0 to 12.0)     Week 80: Neurologist 1.0 (1.0 to 1.0) 2.0 (2.0 to 2.0) 2.5 (2.0 to 3.0) 2.0 (2.0 to 2.0) 2.0 (1.0 to 3.0)     Week 80: Rheumatologist 1.0 (1.0 to 1.0) 1.0 (1.0 to 1.0) 1.0 (1.0 to 2.0) 1.0 (1.0 to 1.0) 1.0 (1.0 to 1.0)     Week 80: Physician assistant or nurse Practitioner 5.0 (1.0 to 9.0) 50.5 (1.0 to 100.0) 1.0 (1.0 to 3.0) 1.0 (1.0 to 1.0) 2.0 (2.0 to 2.0)     Week 80: Pain specialist 2.0 (1.0 to 2.0) 1.0 (1.0 to 11.0) 2.5 (1.0 to 4.0) 1.0 (1.0 to 3.0) 1.0 (1.0 to 3.0)     Week 80: Orthopedist 1.0 (1.0 to 2.0) 2.0 (1.0 to 6.0) 1.0 (1.0 to 3.0) 1.5 (1.0 to 2.0) 1.5 (1.0 to 7.0)     Week 80: Physical therapist 5.0 (1.0 to 8.0) 12.0 (1.0 to 20.0) 4.0 (1.0 to 16.0) 5.0 (1.0 to 20.0) 6.0 (6.0 to 14.0)     Week 80: Chiropractor 401.0 (1.0 to 801.0) 3.5 (1.0 to 9.0) 4.0 (1.0 to 10.0) 4.0 (1.0 to 20.0) 3.0 (1.0 to 14.0)     Week 80: Alternative medicine or therapy 9.0 (3.0 to 15.0) 2.5 (1.0 to 30.0) 3.0 (1.0 to 4.0) 2.5 (2.0 to 3.0) 2.0 (1.0 to 5.0)     Week 80: Podiatrist 1.0 (1.0 to 1.0) 1.0 (1.0 to 1.0) 1.0 (1.0 to 1.0) 1.0 (1.0 to 1.0) 1.5 (1.0 to 2.0)     Week 80: Nutritionist/dietitian 1.0 (1.0 to 1.0) 10.0 (10.0 to 10.0) 1.0 (1.0 to 1.0) 4.0 (2.0 to 6.0) 99999 (99999 to 99999)     Week 80: Radiologist 1.0 (1.0 to 1.0) 99999 (99999 to 99999) 1.5 (1.0 to 2.0) 1.0 (1.0 to 2.0) 1.0 (1.0 to 1.0)     Week 80: Home healthcare services 1.0 (1.0 to 1.0) 99999 (99999 to 99999) 4.0 (4.0 to 4.0) 99999 (99999 to 99999) 24.5 (13.0 to 36.0)     Week 80: Other practitioner 1.0 (1.0 to 11.0) 1.0 (1.0 to 2.0) 1.0 (1.0 to 4.0) 1.0 (1.0 to 3.0) 1.0 (1.0 to 10.0)
No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain Top of page

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Visited the Emergency Room Due to Low Back Pain Top of page
End point title	Health Care Resource Utilization (HCRU): Number of Subjects who Visited the Emergency Room Due to Low Back Pain [42]
End point description	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of subjects who visited the emergency room due to low back pain. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, “n” subjects evaluable for OM at specified time points.
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: subjects     Baseline(n=202,204,407,407,605) 10 14 27 17 26     Week 64(n=135, 138, 285,285,414) 4 2 7 5 3     Week 80(n= 61, 59,134, 143, 191) 0 3 3 0 4
No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Visited the Emergency Room Due to Low Back Pain Top of page

Secondary: Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Low Back Pain Top of page
End point title	Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Low Back Pain [43]
End point description	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of visits to the emergency room due to low back pain. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, “n” subjects evaluable for end point at specified time points.
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: visits median (full range (min-max))     Baseline(n=10, 14, 27, 17, 26) 1.0 (1.0 to 3.0) 1.0 (1.0 to 6.0) 1.0 (1.0 to 4.0) 1.0 (1.0 to 5.0) 1.0 (1.0 to 7.0)     Week 64(n=4, 2, 7, 5, 3) 1.0 (1.0 to 1.0) 2.0 (2.0 to 2.0) 1.0 (1.0 to 3.0) 1.0 (1.0 to 6.0) 1.0 (1.0 to 2.0)     Week 80(n= 0, 3, 3, 0, 4) 99999 (99999 to 99999) 1.0 (1.0 to 11.0) 1.0 (1.0 to 2.0) 99999 (99999 to 99999) 1.5 (1.0 to 2.0)
No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Low Back Pain Top of page

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects Hospitalized Due to Low Back Pain Top of page
End point title	Health Care Resource Utilization (HCRU): Number of Subjects Hospitalized Due to Low Back Pain [44]
End point description	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of subjects who were hospitalized due to low back pain. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, ‘n’= subjects evaluable for this end point at specified time points.
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: subjects     Baseline(n=202, 204, 406,407,605) 0 0 1 0 4     Week 64(n=135,138,285,285,413) 0 0 0 1 1     Week 80(n=61, 59,134,143,191) 0 1 1 0 1
No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects Hospitalized Due to Low Back Pain Top of page

Secondary: Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain Top of page
End point title	Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain [45]
End point description	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of nights stayed in the hospital due to low back pain. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, ‘n’= subjects evaluable for this end point at specified time points and 99999 signifies that no data evaluable.
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: nights median (full range (min-max))     Baseline(n=0, 0, 1, 0, 4) 99999 (99999 to 99999) 99999 (99999 to 99999) 9.0 (9.0 to 9.0) 99999 (99999 to 99999) 1.0 (1.0 to 2.0)     Week 64(n=0, 0, 0, 1, 1) 99999 (99999 to 99999) 99999 (99999 to 99999) 99999 (99999 to 99999) 1.0 (1.0 to 1.0) 1.0 (1.0 to 1.0)     Week 80(n= 0, 1, 1, 0, 1) 99999 (99999 to 99999) 3.0 (3.0 to 3.0) 2.0 (2.0 to 2.0) 99999 (99999 to 99999) 2.0 (2.0 to 2.0)
No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain Top of page

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Used Any Aids/Devices for Doing Things Top of page
End point title	Health Care Resource Utilization (HCRU): Number of Subjects who Used Any Aids/Devices for Doing Things [46]
End point description	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of subjects who used any aids/devices for doing things. Aids such as walking aid, wheelchair, device or utensil for dress/bathe/eat and any other aids/devices. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo).
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: subjects     Baseline:Walking aid useNever 186 190 376 371 569     Baseline:Wheelchair useNever 199 204 403 405 601     Baseline:Device/Utensil to dress bathe eatNever 192 196 390 396 596     Baseline:Other aids or devicesNever 188 188 387 382 550     Week 64:Walking aid useNever 125 131 277 273 397     Week 64:Wheelchair useNever 135 138 283 283 412     Week 64:Device/Utensil to dress bathe eatNever 134 137 283 280 410     Week 64:Other aids or devicesNever 125 135 277 273 387     Week 80:Walking aid useNever 55 56 130 141 182     Week 80:Wheelchair useNever 61 59 134 142 190     Week 80:Device/Utensil to dress bathe eatNever 60 57 132 142 190     Week 80:Other aids or devicesNever 57 58 128 139 184     Baseline:Walking aid useRarely 2 2 11 9 7     Baseline:Wheelchair useRarely 1 0 3 0 1     Baseline:Device/Utensil to dress bathe eatRarely 0 1 1 1 0     Baseline:Other aids or devicesRarely 1 2 2 5 8     Week 64:Walking aid useRarely 2 4 1 3 3     Week 64:Wheelchair useRarely 0 0 1 1 0     Week 64:Device/Utensil to dress bathe eatRarely 0 0 0 2 0     Week 64:Other aids or devicesRarely 1 1 0 0 9     Week 80:Walking aid useRarely 0 0 1 1 2     Week 80:Wheelchair useRarely 0 0 0 1 0     Week 80:Device/Utensil to dress bathe eatRarely 0 1 0 1 1     Week 80:Other aids or devicesRarely 1 1 1 1 0     Baseline:Walking aid useSometimes 6 4 12 16 15     Baseline:Wheelchair useSometimes 2 0 0 2 3     Baseline:Device/Utensil todress bathe eatSometimes 4 3 6 4 4     Baseline:Other aids or devicesSometimes 2 5 10 11 27     Week 64:Walking aid useSometimes 5 1 2 5 9     Week 64:Wheelchair useSometimes 0 0 1 0 1     Week 64:DeviceUtensil to dress bathe eatSometimes 0 0 2 3 2     Week 64:Other aids or devicesSometimes 5 1 5 7 8     Week 80:Walking aid useSometimes 3 1 1 1 4     Week 80:Wheelchair useSometimes 0 0 0 0 0     Week 80:Device/Utensil to dress bathe eatSometimes 1 1 0 0 0     Week 80:Other aids or devicesSometimes 1 0 1 3 3     Baseline:Walking aid useOften 6 5 4 7 9     Baseline:Wheelchair useOften 0 0 0 0 0     Baseline:DeviceUtensil to dress bathe eat|Often 5 1 6 3 4     Baseline:Other aids or devicesOften 10 5 4 6 17     Week 64:Walking aid useOften 1 0 3 3 2     Week 64:Wheelchair useOften 0 0 0 0 1     Week 64:Device/Utensil to dress bathe eatOften 0 1 0 0 0     Week 64:Other aids or devicesOften 2 1 1 3 7     Week 80:Walking aid useOften 2 1 1 0 2     Week 80:Wheelchair useOften 0 0 0 0 0     Week80:Device/Utensil to dress bathe eatOften 0 0 1 0 0     Week 80:Other aids or devicesOften 2 0 1 0 2     Baseline:Walking aid useAlways 2 3 3 4 5     Baseline: Wheelchair useAlways 0 0 0 0 0     Baseline:Device/Utensil to dress bathe eatAlways 1 3 3 3 1     Baseline:Other aids or devicesAlways 1 4 3 3 3     Week 64:Walking aid useAlways 2 2 2 1 3     Week 64: Wheelchair useAlways 0 0 0 1 0     Week64:Device/Utensil to dress bathe eatAlways 1 0 0 0 2     Week 64:Other aids or devicesAlways 2 0 2 2 3     Week 80: Walking aid useAlways 1 1 1 0 1     Week 80: Wheelchair useAlways 0 0 0 0 1     Week80:Device/Utensil to dress bathe eatAlways 0 0 1 0 0     Week80:Other aids or devicesAlways 0 0 3 0 2
No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Used Any Aids/Devices for Doing Things Top of page

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Quit Job Due to Low Back Pain Top of page
End point title	Health Care Resource Utilization (HCRU): Number of Subjects who Quit Job Due to Low Back Pain [47]
End point description	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of subjects who quit job due to low back pain. ITT population included all randomized subjects who received at least 1 dose of SC study medication (either tanezumab or matching placebo). Here, ‘n’= subjects evaluable for this end point at specified time points.
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: subjects     Baseline(n= 17, 15, 28, 31, 47) 17 14 28 31 47     Week 64(n= 6, 3, 14, 10, 21) 6 2 11 8 14     Week 80(n= 4, 2, 4, 3, 3) 4 2 4 3 3
No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Quit Job Due to Low Back Pain Top of page

Secondary: Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Low Back Pain Top of page
End point title	Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Low Back Pain [48]
End point description	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was duration since quitting job due to low back pain.
End point type	Secondary
End point timeframe	Baseline, Weeks 64 and 80
Notes [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Placebo Followed by Tanezumab 5 mg Placebo Followed by Tanezumab 10 mg Tanezumab 5 mg Tanezumab 10 mg Tramadol PR Number of subjects analysed 202 204 407 407 605 Units: years median (full range (min-max))     Baseline 2.0 (0.2 to 15.0) 2.0 (0.3 to 15.6) 1.0 (0.1 to 20.5) 3.8 (0.1 to 16.0) 2.3 (0.1 to 90.3)     Week 64 1.1 (0.1 to 13.2) 5.2 (2.5 to 7.1) 2.2 (0.2 to 32.0) 2.0 (0.1 to 17.0) 2.5 (0.1 to 25.2)     Week 80 8.6 (5.8 to 99.1) 4.7 (1.0 to 8.3) 0.2 (0.0 to 3.3) 3.5 (0.8 to 17.1) 3.5 (3.0 to 5.0)
No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Low Back Pain Top of page

Secondary: Treatment Satisfaction Score Determined With Treatment Satisfaction Questionnaire for Medication Version II (TSQM v II) at Weeks 16 and 56 Top of page
End point title	Treatment Satisfaction Score Determined With Treatment Satisfaction Questionnaire for Medication Version II (TSQM v II) at Weeks 16 and 56 [49]
End point description	TSQM v.II: self-administered 11-item validated scale that quantified subject’s level of satisfaction with study medication (7 questions scored on 7-point Likert scale [1= extremely dissatisfied, 2=very dissatisfied, 3=dissatisfied, 4=somewhat satisfied, 5=satisfied, 6=very satisfied, 7=extremely satisfied]), effectiveness and side effects/tolerability (3 questions scored on 5 point Likert scale [1= extremely dissatisfied, 2=very dissatisfied, 3=somewhat dissatisfied, 4=slightly dissatisfied, 5=not at all dissatisfied], 1 question on 2 point scale [0 =No, 1=Yes]). 11 questions of TSQM were used to calculate 4 endpoints of effectiveness, side effects, convenience and global satisfaction, each scored on a 0-100 scale with 100=best level of satisfaction. Pre-specified intent of study for efficacy data up to Week 16 was to analyze subject who received placebo from Day 1 and tanezumab 5/10 mg at week 16 in placebo arm. Hence data have been reported per 4 arms. ITT population was used.
End point type	Secondary
End point timeframe	Weeks 16 and 56
Notes [49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: units on a scale least squares mean (standard error)     Week16:Effectiveness(n= 338, 343, 329, 456) 63.69 ( 1.48 ) 62.87 ( 1.48 ) 56.67 ( 1.50 ) 61.39 ( 1.30 )     Week16:Side Effects(n= 49, 49, 39, 120) 79.26 ( 3.31 ) 79.51 ( 3.31 ) 66.95 ( 3.76 ) 70.83 ( 2.15 )     Week16:Convenience(n= 338, 343, 329, 456) 75.68 ( 1.16 ) 76.37 ( 1.15 ) 73.11 ( 1.16 ) 74.63 ( 1.04 )     Week16:Global Satisfaction(n= 338, 343, 329, 456) 70.32 ( 1.39 ) 68.64 ( 1.38 ) 64.90 ( 1.41 ) 67.12 ( 1.22 )     Week56:Effectiveness(n= 141, 159, 0, 206) 72.66 ( 2.12 ) 72.51 ( 2.01 ) 99999 ( 99999 ) 71.21 ( 1.79 )     Week56:Side Effects(n= 9, 17, 0, 41) 78.92 ( 6.32 ) 89.37 ( 4.76 ) 99999 ( 99999 ) 76.20 ( 3.09 )     Week56:Convenience(n= 141, 159, 0, 206) 78.72 ( 1.69 ) 80.52 ( 1.60 ) 99999 ( 99999 ) 78.42 ( 1.45 )     Week56:Global Satisfaction(n= 141, 159, 0, 206) 78.11 ( 1.83 ) 78.49 ( 1.73 ) 99999 ( 99999 ) 74.57 ( 1.55 )
Statistical analysis title	Pooled Placebo, Tanezumab 5 mg
Statistical analysis description	TSQM Effectiveness; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0005
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	7.02
Confidence interval
level	95%
sides	2-sided
lower limit	3.07
upper limit	10.97
Variability estimate	Standard error of the mean
Dispersion value	2.01
Statistical analysis title	Pooled Placebo Versus Tanezumab 10 mg
Statistical analysis description	TSQM Effectiveness; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0021
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	6.21
Confidence interval
level	95%
sides	2-sided
lower limit	2.26
upper limit	10.15
Variability estimate	Standard error of the mean
Dispersion value	2.01
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	TSQM Effectiveness; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0125
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	4.72
Confidence interval
level	95%
sides	2-sided
lower limit	1.02
upper limit	8.42
Variability estimate	Standard error of the mean
Dispersion value	1.89
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	TSQM Effectiveness; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2176
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	2.31
Confidence interval
level	95%
sides	2-sided
lower limit	-1.36
upper limit	5.97
Variability estimate	Standard error of the mean
Dispersion value	1.87
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	TSQM Effectiveness; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4235
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	1.49
Confidence interval
level	95%
sides	2-sided
lower limit	-2.16
upper limit	5.14
Variability estimate	Standard error of the mean
Dispersion value	1.86
Statistical analysis title	Tanezumab 5 mg Versus Pooled Placebo
Statistical analysis description	TSQM Side Effects; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0143
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	12.3
Confidence interval
level	95%
sides	2-sided
lower limit	2.5
upper limit	22.11
Variability estimate	Standard error of the mean
Dispersion value	4.96
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	TSQM Side Effects; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0124
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	12.55
Confidence interval
level	95%
sides	2-sided
lower limit	2.76
upper limit	22.35
Variability estimate	Standard error of the mean
Dispersion value	4.96
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	TSQM Side Effects; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3675
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	3.88
Confidence interval
level	95%
sides	2-sided
lower limit	-4.6
upper limit	12.36
Variability estimate	Standard error of the mean
Dispersion value	4.29
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	TSQM Side Effects; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0319
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	8.42
Confidence interval
level	95%
sides	2-sided
lower limit	0.74
upper limit	16.11
Variability estimate	Standard error of the mean
Dispersion value	3.89
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	TSQM Side Effects; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0276
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	8.67
Confidence interval
level	95%
sides	2-sided
lower limit	0.97
upper limit	16.38
Variability estimate	Standard error of the mean
Dispersion value	3.9
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	TSQM Convenience; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0627
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	2.57
Confidence interval
level	95%
sides	2-sided
lower limit	-0.14
upper limit	5.27
Variability estimate	Standard error of the mean
Dispersion value	1.38
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	TSQM Convenience; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0187
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	3.26
Confidence interval
level	95%
sides	2-sided
lower limit	0.54
upper limit	5.97
Variability estimate	Standard error of the mean
Dispersion value	1.38
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	TSQM Convenience; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2419
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	1.52
Confidence interval
level	95%
sides	2-sided
lower limit	-1.03
upper limit	4.06
Variability estimate	Standard error of the mean
Dispersion value	1.3
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	TSQM Convenience; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.4124
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	1.05
Confidence interval
level	95%
sides	2-sided
lower limit	-1.46
upper limit	3.56
Variability estimate	Standard error of the mean
Dispersion value	1.28
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	TSQM Convenience; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.173
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	1.74
Confidence interval
level	95%
sides	2-sided
lower limit	-0.76
upper limit	4.24
Variability estimate	Standard error of the mean
Dispersion value	1.27
Statistical analysis title	Pooled Placebo Versus Tanezumab 5 mg
Statistical analysis description	TSQM Global Satisfaction; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0037
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	5.42
Confidence interval
level	95%
sides	2-sided
lower limit	1.77
upper limit	9.08
Variability estimate	Standard error of the mean
Dispersion value	1.86
Statistical analysis title	Tanezumab 10 mg Versus Pooled Placebo
Statistical analysis description	TSQM Global Satisfaction; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Placebo
Number of subjects included in analysis	813
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0449
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	3.74
Confidence interval
level	95%
sides	2-sided
lower limit	0.09
upper limit	7.39
Variability estimate	Standard error of the mean
Dispersion value	1.86
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	TSQM Global Satisfaction; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Placebo v Tramadol PR
Number of subjects included in analysis	1011
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2038
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	2.22
Confidence interval
level	95%
sides	2-sided
lower limit	-1.21
upper limit	5.65
Variability estimate	Standard error of the mean
Dispersion value	1.75
Statistical analysis title	Pooled Placebo Versus Tramadol PR
Statistical analysis description	TSQM Global Satisfaction; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0644
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	3.2
Confidence interval
level	95%
sides	2-sided
lower limit	-0.19
upper limit	6.59
Variability estimate	Standard error of the mean
Dispersion value	1.73
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	TSQM Global Satisfaction; Week 16: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.3775
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	1.52
Confidence interval
level	95%
sides	2-sided
lower limit	-1.86
upper limit	4.9
Variability estimate	Standard error of the mean
Dispersion value	1.72
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	TSQM Effectiveness; Week 56: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.5806
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	1.45
Confidence interval
level	95%
sides	2-sided
lower limit	-3.7
upper limit	6.6
Variability estimate	Standard error of the mean
Dispersion value	2.62
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	TSQM Effectiveness; Week 56: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6084
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	1.45
Confidence interval
level	95%
sides	2-sided
lower limit	-3.68
upper limit	6.6
Variability estimate	Standard error of the mean
Dispersion value	2.53
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	TSQM Side Effects; Week 56: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.6991
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	2.71
Confidence interval
level	95%
sides	2-sided
lower limit	-11.56
upper limit	16.99
Variability estimate	Standard error of the mean
Dispersion value	6.95
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	TSQM Side Effects; Week 56: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0265
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	13.17
Confidence interval
level	95%
sides	2-sided
lower limit	1.66
upper limit	24.68
Variability estimate	Standard error of the mean
Dispersion value	5.6
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	TSQM Convenience; Week 56: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.8795
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	0.3
Confidence interval
level	95%
sides	2-sided
lower limit	-3.61
upper limit	4.21
Variability estimate	Standard error of the mean
Dispersion value	1.99
Statistical analysis title	Tanezumab 10 mg Versus Tramadol PR
Statistical analysis description	TSQM Convenience; Week 56: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.2758
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	2.1
Confidence interval
level	95%
sides	2-sided
lower limit	-1.68
upper limit	5.87
Variability estimate	Standard error of the mean
Dispersion value	1.92
Statistical analysis title	Tanezumab 5 mg Versus Tramadol PR
Statistical analysis description	TSQM Global Satisfaction; Week 56: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 5 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.1197
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	3.54
Confidence interval
level	95%
sides	2-sided
lower limit	-0.92
upper limit	8
Variability estimate	Standard error of the mean
Dispersion value	2.27
Statistical analysis title	Tanezumab 10 mg versus Tramadol PR
Statistical analysis description	TSQM Global Satisfaction; Week 56: p-value was computed using ANCOVA with covariates of baseline average LBPI score, treatment, and study site as a random effect.
Comparison groups	Tanezumab 10 mg v Tramadol PR
Number of subjects included in analysis	1012
Analysis specification	Pre-specified
Analysis type	superiority
P-value	> 0.0743
Method	ANCOVA
Parameter type	LS Mean Difference
Point estimate	3.93
Confidence interval
level	95%
sides	2-sided
lower limit	-0.39
upper limit	8.24
Variability estimate	Standard error of the mean
Dispersion value	2.19

Secondary: Treatment Satisfaction Score Determined With Treatment Satisfaction Questionnaire for Medication Version II (TSQM v II) at Weeks 16 and 56 Top of page

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Low Back Pain Before Enrolling? Top of page
End point title	Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Low Back Pain Before Enrolling? [50]
End point description	mPRTI:self-administered questionnaire containing subject reported treatment impact assessment, subject global preference assessment and subject willingness to use drug again assessment. To assess previous treatment, subjects responded for, 1=injectable prescription medicines(PM), 2=PM taken by mouth, 3=surgery, 4=PM and surgery and 5=no treatment.Pre-specified intent of study for efficacy data up to W16 was to analyze, subjects received placebo from Day 1 and received tan 5/10 mg at week 16 in placebo arm, in pooled manner.Data have been reported per 4 arms.ITT population. Pre-specified intent of study was to compare tan Vs placebo for data up to and including week 16 and comparisons of tan Vs tramadol for data up to and including week 56. Hence, number analyzed is 0 for placebo arm for week 16 and onwards. Here “n” =subjects who were evaluable at specified time point.
End point type	Secondary
End point timeframe	Weeks 16 and 56
Notes [50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: subjects     Week16:InjectablePM(n= 333,340,322, 450) 21 22 20 39     Week56:InjectablePM(n=141, 159, 0, 206) 6 13 0 9     Week16:PMtaken by mouth(n= 333,340, 322,450) 211 229 213 287     Week56:PMtaken by mouth(n= 141, 159, 0, 206) 91 102 0 147     Week16:Surgery(n= 333,340,322, 450) 2 1 2 1     Week 56:Surgery(n= 141, 159, 0, 206) 2 0 0 3     Week 16:PM and surgery(n= 333,340,322,450) 9 10 7 14     Week 56:PM and surgery(n= 141, 159,0, 206) 7 4 0 3     Week 16:No treatment(n= 333,340, 322,450) 90 78 80 109     Week 56:No treatment(n= 141, 159, 0, 206) 35 40 0 44
No statistical analyses for this end point

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Low Back Pain Before Enrolling? Top of page

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment? Top of page
End point title	Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment? [51]
End point description	mPRTI:self-administered questionnaire containing subject reported treatment impact assessment, subject GPA & subject willingness to use drug again assessment.Subjects responded using IRT on 5 point scale from 1-5,1= yes,I would definitely want to use same drug again(SDA),2= I might want to use SDA,3= I am not sure,4= I might not want to use SDA,5=no, I definitely would not want to use SDA.Higher scores indicate lesser willingness to use the investigational product.Pre-specified intent of study for efficacy data up to Week 16 was to analyze, subjects who received placebo from Day 1 & received tan 5/10 mg at week 16 in placebo arm, in pooled manner.Data have been reported per 4 arms.ITT.Pre-specified intent of study was to compare tan Vs placebo for data up to and W16 and comparisons of tan Vs tramadol for data up to and including W56.Number analyzed is 0 for placebo arm for W16 and onwards.Here “n” =subjects evaluable at specified time point. '99999' =no subjects evaluable.
End point type	Secondary
End point timeframe	Weeks 16 and 56
Notes [51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: subjects     W16Yes surely prefer study drug(n=340,406,333,605) 172 191 150 232     W56Yes surely prefer study drug(n=141,159,0,206) 90 104 99999 129     W16Prefer slightly study drug(n=340,406,333,605) 62 50 57 89     W56Prefer slightly study drug(n =141,159,0,206) 30 36 99999 42     W16No preference either way(n =340, 406, 333, 605) 66 55 62 82     W56No preference either way(n =141, 159, 0, 206) 15 12 99999 22     W16Prefer slightly old drug(n=340,406,333,605) 14 23 24 17     W56Prefer slightly old drug(n =141, 159, 0, 206) 2 4 99999 7     W16No surely prefer old drug(n=340,406,333,605) 19 21 29 30     W56No surely prefer old drug(n=141,159,0,206) 4 3 99999 6
No statistical analyses for this end point

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment? Top of page

Secondary: Subject Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Low Back Pain Pain? Top of page
End point title	Subject Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Low Back Pain Pain? [52]
End point description	mPRTI:self-administered questionnaire containing subject reported treatment impact assessment, subject GPA & subject willingness to use drug again assessment. Subjects responded using IRT on 5 point scale from 1-5,1= yes, I would definitely want to use same drug again(SDA), 2= I might want to use SDA, 3= I am not sure, 4= I might not want to use SDA,5= no, I definitely would not want to use SDA. Higher scores indicate lesser willingness to use the investigational product. Pre-specified intent of study for efficacy data up to Week 16 was to analyze, subjects who received placebo from Day 1 & received tan 5/10 mg at week 16 in placebo arm, in pooled manner. Data have been reported per four arms. ITT.Pre-specified intent of study was to compare tan Vs placebo for data up to and including week 16 and comparisons of tan Vs tramadol for data up to and including week 56.Number analyzed is 0 for placebo arm for week 16 and onwards. Here “n” =subjects evaluable at specified time point.
End point type	Secondary
End point timeframe	Weeks 16 and 56
Notes [52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tanezumab 10 mg Placebo Tramadol PR Number of subjects analysed 407 407 406 605 Units: subjects     W16Yes surely want to use SDA(n= 322, 333,340,450) 191 210 167 251     W56Yes surely want to use SDA(n= 0,141,159,206) 99 114 0 133     W16Might want to use SDA(n= 322, 333,340,450) 80 58 61 98     W56Might want to use SDA(n= 0, 141, 159, 206) 23 31 0 41     W16 I am not sure(n= 322, 333,340,450) 36 38 51 64     W56 I am not sure(n= 0, 141, 159, 206) 15 10 0 26     W16:Might not want to use SDA(n= 322, 333,340,450) 10 13 11 13     W56:Might not want to use SDA(n= 0, 141, 159, 206) 0 2 0 4     W16Surely not want to use SDA(n=322,333,340,450) 16 21 32 24     W56Surely not want to use SDA(= 0, 141, 159, 206) 4 2 0 2
No statistical analyses for this end point

Secondary: Subject Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Subject Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Low Back Pain Pain? Top of page

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to End of Study Top of page
End point title	Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to End of Study
End point description	An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to week 48 that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. Safety population was analyzed. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to and including week 16 and comparisons of tan Vs tram for data up to and including week 56. Hence, number analyzed is 0 for placebo arm for week 16 and onwards. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this endpoint.
End point type	Secondary
End point timeframe	Baseline up to Week 80
End point values Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Tramadol PR Number of subjects analysed 215 506 502 602 Units: subjects     AEs 125 319 347 421     SAEs 7 21 37 25
No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to End of Study Top of page

Secondary: Number of Subjects With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Top of page
End point title	Number of Subjects With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [53]
End point description	Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to week 56 that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, “N”=subjects evaluable for this endpoint.
End point type	Secondary
End point timeframe	Baseline up to Week 56
Notes [53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Number of subjects analysed 602 506 502 Units: subjects     AEs 200 105 119     SAEs 1 1 4
No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Top of page

Secondary: Number of Subjects With Laboratory Test Abnormalities With Regard to Normal Baseline Top of page
End point title	Number of Subjects With Laboratory Test Abnormalities With Regard to Normal Baseline [54]
End point description	Abnormality criteria:HGB,hematocrit,RBC count <0.8* LLN;Ery. mean corpuscular volume/hemoglobin/ HGB concentration,RBCs distribution width <0.9*LLN, >1.1* ULN; platelets <0.5*LLN, >1.75*ULN;WBC count<0.6*LLN, >1.5*ULN;Lymphocytes, Leukocytes, Neutrophils <0.8*LLN, >1.2*ULN; Basophils,Eosinophils, Monocytes>1.2*ULN;Prothrombin time/Intl. normalized ratio>1.1*ULN;total bilirubin >1.5*ULN; aspartate aminotransferase,alanine aminotransferase,gamma GT,LDH,alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen, creatinine, cholesterol, triglycerides >1.3*ULN; Urate>1.2*ULN; sodium<0.95*LLN, >1.05*ULN; potassium, chloride,calcium,magnesium,bicarbonate <0.9*LLN, >1.1*ULN;phosphate<0.8*LLN, >1.2*ULN; glucose<0.6*LLN, >1.5*ULN; HGB A1C >1.3*ULN; creatine kinase>2.0*ULN, specific gravity<1.003, >1.030; pH<4.5, >8; Urine Glucose, protein,HGB,bilirubin>=1; Ketones>=1;Urine erythrocytes,Leukocytes>=20.Safety population.“N”=subjects evaluable for this endpoint.
End point type	Secondary
End point timeframe	Baseline up to Week 80
Notes [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Placebo Tanezumab 10 mg Pooled Tanezumab 5 mg Pooled Number of subjects analysed 488 129 433 434 Units: subjects 59 16 61 56
No statistical analyses for this end point

Secondary: Number of Subjects With Laboratory Test Abnormalities With Regard to Normal Baseline Top of page

Secondary: Number of Subjects With Laboratory Test Abnormalities With Regard to Abnormal Baseline Top of page
End point title	Number of Subjects With Laboratory Test Abnormalities With Regard to Abnormal Baseline [55]
End point description	Abnormality criteria:hemoglobin;hematocrit; RBC count <0.8*LLN; Ery. mean corpuscular volume/ hemoglobin/ HGB concentration, erythrocytes distribution width <0.9*LLN, >1.1*ULN; platelets <0.5*LLN,>1.75*ULN; white blood cell count<0.6*LLN, >1.5*ULN; Lymphocytes, Leukocytes, Neutrophils <0.8*LLN, >1.2*ULN; Basophils, Eosinophils, Monocytes >1.2*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase, alanine aminotransferase, gamma GT,LDH, alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen, creatinine, Cholesterol, triglycerides >1.3*ULN; Urate >1.2*ULN; sodium <0.95*LLN,>1.05*ULN; potassium, chloride, calcium, magnesium, bicarbonate <0.9*LLN, >1.1*ULN; phosphate <0.8*LLN, >1.2*ULN; glucose <0.6*LLN, >1.5*ULN; Hemoglobin A1C >1.3*ULN; creatine kinase >2.0*ULN; Nitrite >=1.Safety population: all subjects treated with tanezumab or placebo SC. Here “Number of subjects analysed” signifies subjects who were evaluable for this endpoint.
End point type	Secondary
End point timeframe	Baseline up to Week 80
Notes [55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tramadol Tanezumab 10 mg Pooled Placebo Number of subjects analysed 332 373 308 92 Units: subjects 40 45 39 11
No statistical analyses for this end point

Secondary: Number of Subjects With Laboratory Test Abnormalities With Regard to Abnormal Baseline Top of page

Secondary: Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 Top of page
End point title	Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 [56]
End point description	Measurement of BP included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP). The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, “Number of subjects analyzed”= subjects evaluable for this endpoint and “n”= subjects who were evaluable for specified categories. '99999' = signifies that no subjects were evaluable, hence mean and standard deviation not applicable.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
Notes [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Number of subjects analysed 602 215 506 502 Units: millimeters of mercury (mmHg) arithmetic mean (standard deviation)     SBP: Baseline (n =602, 215, 506, 502) 123.7 ( 13.77 ) 122.3 ( 12.20 ) 123.8 ( 13.25 ) 122.6 ( 12.36 )     SBP:Change at Week 2 (n =560, 191, 488, 478) -1.4 ( 11.37 ) -1.3 ( 10.50 ) -2.0 ( 11.05 ) -1.4 ( 10.62 )     SBP:Change at Week 4 (n =535, 173, 473, 468) -1.8 ( 11.81 ) -2.1 ( 11.36 ) -2.2 ( 11.46 ) -1.7 ( 10.65 )     SBP:Change at Week 8 (n =490, 152, 454, 450) -1.7 ( 11.99 ) -1.1 ( 11.37 ) -1.0 ( 11.38 ) -2.2 ( 11.02 )     SBP:Change at Week 16 (n =314, 8, 340, 344) -1.6 ( 11.96 ) -0.5 ( 10.56 ) -2.2 ( 10.75 ) -1.4 ( 11.10 )     SBP:Change at Week 24 (n =269, 0, 288, 295) -1.9 ( 12.57 ) 99999 ( 99999 ) -2.2 ( 10.51 ) -1.8 ( 11.53 )     SBP:Change at Week 32 (n =229, 0, 240, 255) -2.2 ( 12.54 ) 99999 ( 99999 ) -0.6 ( 11.36 ) -1.4 ( 11.53 )     SBP:Change at Week 40 (n = 218, 0, 218, 239) -1.0 ( 11.99 ) 99999 ( 99999 ) -2.0 ( 11.27 ) -1.6 ( 11.91 )     SBP:Change at Week 48 (n = 208, 0, 211, 229) -0.8 ( 12.46 ) 99999 ( 99999 ) -2.0 ( 12.12 ) -2.2 ( 11.51 )     SBP:Change at Week 56 (n = 204, 0, 202, 222) -1.1 ( 12.03 ) 99999 ( 99999 ) -1.5 ( 11.18 ) -3.0 ( 12.03 )     SBP:Change at Week 64 (n =195, 0, 199, 209) -1.2 ( 11.59 ) 99999 ( 99999 ) -0.9 ( 11.51 ) -1.9 ( 12.28 )     SBP:Change at Week 80 (n =191, 0, 193, 201) -1.0 ( 11.77 ) 99999 ( 99999 ) -1.4 ( 10.82 ) 0.1 ( 12.62 )     DBP: Baseline (n =602, 215, 506, 502) 78.2 ( 9.01 ) 77.9 ( 9.10 ) 78.6 ( 8.98 ) 77.4 ( 8.48 )     DBP:Change at Week 2 (n =560, 191, 488, 478) -0.7 ( 8.21 ) -1.2 ( 7.63 ) -1.1 ( 7.49 ) -1.5 ( 7.91 )     DBP:Change at Week 4 (n =535, 173, 473, 468) -0.9 ( 7.94 ) -1.7 ( 7.59 ) -1.5 ( 7.75 ) -1.1 ( 7.59 )     DBP:Change at Week 8 (n =490, 152, 454, 450) -0.8 ( 8.13 ) 0.0 ( 7.24 ) -1.2 ( 8.04 ) -1.5 ( 8.26 )     DBP:Change at Week 16 (n =314, 8, 340, 344) -0.8 ( 8.15 ) -0.6 ( 5.63 ) -1.2 ( 8.21 ) -1.0 ( 8.39 )     DBP:Change at Week 24 (n =269, 0, 288, 295) -1.0 ( 7.76 ) 99999 ( 99999 ) -1.2 ( 8.04 ) -0.8 ( 8.13 )     DBP:Change at Week 32 (n =229, 0, 240, 255) -0.4 ( 8.39 ) 99999 ( 99999 ) -0.6 ( 7.80 ) -0.5 ( 8.10 )     DBP:Change at Week 40 (n = 218, 0, 218, 239) -0.7 ( 8.36 ) 99999 ( 99999 ) -1.4 ( 8.56 ) -1.1 ( 8.13 )     DBP:Change at Week 48 (n = 208, 0, 211, 229) -0.7 ( 7.93 ) 99999 ( 99999 ) -2.1 ( 9.05 ) -1.3 ( 8.23 )     DBP:Change at Week 56 (n = 204, 0, 202, 222) -0.7 ( 7.93 ) 99999 ( 99999 ) -2.1 ( 9.05 ) -1.3 ( 8.23 )     DBP:Change at Week 64 (n =195, 0, 199, 209) -0.6 ( 8.95 ) 99999 ( 99999 ) -0.7 ( 8.03 ) -0.0 ( 9.13 )     DBP:Change at Week 80 (n =191, 0, 193, 201) -0.1 ( 8.55 ) 99999 ( 99999 ) -1.0 ( 8.13 ) 0.5 ( 9.07 )
No statistical analyses for this end point

Secondary: Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 Top of page

Secondary: Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 Top of page
End point title	Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
End point description	Heart rate was measured at sitting position. The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, “Number of subjects analyzed”= subjects evaluable for this endpoint and “n”= subjects who were evaluable at specified time point for each arm, respectively. '99999' = signifies that no subjects were evaluable, hence mean and standard deviation not applicable.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
End point values Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Tramadol PR Number of subjects analysed 215 506 502 602 Units: beats per minute arithmetic mean (standard deviation)     Baseline (n =215, 506, 502, 602) 73.3 ( 10.86 ) 73.1 ( 10.23 ) 72.5 ( 10.10 ) 73.2 ( 10.61 )     Change at Week 2 (n =191, 488, 478, 560) 0.8 ( 9.14 ) 0.5 ( 9.09 ) 0.3 ( 9.23 ) -0.2 ( 9.24 )     Change at Week 4 (n =173, 473, 468, 535) 1.6 ( 9.32 ) 0.6 ( 8.82 ) 0.4 ( 9.47 ) 0.2 ( 9.57 )     Change at Week 8 (n =152, 454, 450, 490) 1.2 ( 8.88 ) 0.1 ( 9.41 ) -0.1 ( 9.87 ) 0.0 ( 9.89 )     Change at Week 16 (n =8, 340, 344, 314) 5.1 ( 10.66 ) -0.6 ( 9.99 ) -1.0 ( 9.65 ) -0.8 ( 10.13 )     Change at Week 24 (n =0, 288, 295, 269) 99999 ( 99999 ) 0.0 ( 9.32 ) -0.3 ( 9.77 ) 0.2 ( 10.09 )     Change at Week 32 (n =0, 240, 255, 229) 99999 ( 99999 ) 0.5 ( 9.82 ) -0.3 ( 9.94 ) 0.6 ( 9.72 )     Change at Week 40 (n =0, 218, 239, 218) 99999 ( 99999 ) 1.2 ( 10.14 ) -0.5 ( 9.77 ) 1.3 ( 9.55 )     Change at Week 48 (n =0, 211, 229, 208) 99999 ( 99999 ) 0.5 ( 9.72 ) -0.5 ( 10.79 ) 0.9 ( 10.33 )     Change at Week 56 (n =0, 202, 222, 204) 99999 ( 99999 ) 0.4 ( 10.31 ) 0.2 ( 10.50 ) 0.7 ( 11.10 )     Change at Week 64 (n =0, 199, 209, 195) 99999 ( 99999 ) 1.1 ( 10.66 ) 0.8 ( 10.08 ) 0.7 ( 10.22 )     Change at Week 80 (n =0, 193, 201, 191) 99999 ( 99999 ) 1.1 ( 10.93 ) 1.2 ( 9.83 ) 0.9 ( 11.48 )
No statistical analyses for this end point

Secondary: Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 Top of page

Secondary: Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16, 56 and 80 Top of page
End point title	Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16, 56 and 80 [57]
End point description	A 12–lead ECG was recorded after subjects had rested for at least 5 minutes in the supine position in a quiet environment. All standard intervals {RR interval, PR interval, QRS interval, QT interval, QT interval corrected using Bazett's formula (QTcB) and QT interval corrected using Fridericia's formula (QTcF)} were collected. The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, ‘Number of subjects analyzed’ signifies subjects analyzed for this endpoint and ‘n’ = subjects who had at least 1 ADA sample for ADA assessment at specified time points. '99999' = signifies that no subjects were evaluable, hence mean and standard deviation not applicable.
End point type	Secondary
End point timeframe	Baseline, Weeks 16, 56 and 80
Notes [57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Number of subjects analysed 602 215 506 502 Units: millisecond arithmetic mean (standard deviation)     RR Interval: Baseline (n= 602, 215, 506, 502) 918.9 ( 138.55 ) 928.5 ( 150.40 ) 911.4 ( 140.72 ) 915.4 ( 138.41 )     RR Interval:Change at Week 16(n= 308, 6, 338, 335) 894.9 ( 139.62 ) 868.2 ( 235.72 ) 897.1 ( 129.55 ) 912.1 ( 142.81 )     RR Interval:Change at Week 56(n= 202, 0, 200, 221) 881.5 ( 136.11 ) 99999 ( 99999 ) 894.5 ( 138.03 ) 893.0 ( 144.30 )     RR Interval:Change at Week 80(n= 190, 0, 190, 199) 876.5 ( 134.79 ) 99999 ( 99999 ) 870.5 ( 130.84 ) 889.6 ( 143.10 )     PR Interval: Baseline(n= 596, 213, 506, 501) 157.8 ( 23.44 ) 156.2 ( 20.51 ) 157.3 ( 23.32 ) 158.1 ( 22.93 )     PR Interval:CAW 16(n= 308, 6, 337, 334) 158.6 ( 23.37 ) 158.8 ( 12.37 ) 158.3 ( 21.99 ) 159.6 ( 21.84 )     PR Interval:CAW 56(n= 202, 0, 199, 221) 159.2 ( 22.13 ) 99999 ( 99999 ) 158.5 ( 21.78 ) 158.1 ( 20.85 )     PR Interval:CAW 80(n= 189, 0, 190, 198) 158.3 ( 21.46 ) 99999 ( 99999 ) 158.7 ( 22.15 ) 157.7 ( 21.60 )     QRS Interval: Baseline(n= 599, 215, 506, 502) 93.1 ( 12.02 ) 90.9 ( 8.72 ) 92.5 ( 11.06 ) 93.5 ( 12.30 )     QRS Interval:CAW 16(n= 308,6,338, 335) 93.9 ( 12.53 ) 97.0 ( 8.29 ) 93.4 ( 11.95 ) 94.5 ( 13.27 )     QRS Interval:CAW 56(n= 202, 0, 200, 221) 94.2 ( 13.73 ) 99999 ( 99999 ) 92.8 ( 12.71 ) 95.4 ( 12.62 )     QRS Interval:CAW 80(n= 190,0,190,199) 94.4 ( 13.16 ) 99999 ( 99999 ) 93.0 ( 11.55 ) 95.0 ( 12.53 )     QT Interval:Baseline(n=599,215,504, 502) 393.7 ( 29.06 ) 394.7 ( 29.67 ) 393.1 ( 29.52 ) 394.6 ( 27.54 )     QT Interval:CAW 16(n=308,6,337,334) 391.2 ( 30.30 ) 379.8 ( 34.29 ) 391.1 ( 28.13 ) 393.5 ( 29.09 )     QT Interval:CAW 56(n=201,0,200,221) 389.7 ( 29.44 ) 99999 ( 99999 ) 389.3 ( 27.11 ) 392.8 ( 29.47 )     QT Interval:CAW 80(n=190, 0, 190, 198) 388.7 ( 29.33 ) 99999 ( 99999 ) 386.6 ( 27.67 ) 393.0 ( 29.90 )     QTCB Interval:Baseline(n=599,215,504, 502) 412.6 ( 22.39 ) 411.7 ( 20.49 ) 413.5 ( 20.19 ) 414.4 ( 21.60 )     QTCB Interval:CAW 16(n=308,6,337,334) 415.3 ( 20.13 ) 411.8 ( 17.50 ) 414.5 ( 19.76 ) 413.9 ( 22.67 )     QTCB Interval:CAW 56(n=201,0,200,221) 416.8 ( 21.71 ) 99999 ( 99999 ) 413.5 ( 21.27 ) 417.7 ( 22.02 )     QTCB Interval:CAW 80(n=190,0,190,198) 417.0 ( 21.71 ) 99999 ( 99999 ) 416.1 ( 19.27 ) 418.8 ( 22.13 )     QTCF Interval:Baseline(n=599,215,504,502) 405.9 ( 20.28 ) 405.6 ( 18.22 ) 406.3 ( 18.85 ) 407.4 ( 18.93 )     QTCF Interval:CAW16(n=308,6,337,334) 406.8 ( 19.04 ) 400.3 ( 10.69 ) 406.3 ( 18.45 ) 406.7 ( 20.35 )     QTCF Interval:CAW 56(n=201,0,200,221) 407.3 ( 19.74 ) 99999 ( 99999 ) 405.0 ( 18.46 ) 408.9 ( 19.75 )     QTCF Interval:CAW 80(n=190,0,190,198) 407.1 ( 19.81 ) 99999 ( 99999 ) 405.7 ( 17.70 ) 409.7 ( 19.74 )
No statistical analyses for this end point

Secondary: Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16, 56 and 80 Top of page

Secondary: Change From Baseline in Heart Rate (as assessed by ECG) at Weeks 16, 56 and 80 Top of page
End point title	Change From Baseline in Heart Rate (as assessed by ECG) at Weeks 16, 56 and 80
End point description	Heart rate was measured at sitting position. The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, ‘Number of subjects analyzed’ signifies subjects analyzed for this endpoint and ‘n’ = subjects who had at least 1 ADA sample for ADA assessment at specified time points. '99999' = signifies that no subjects were evaluable, hence mean and standard deviation not applicable.
End point type	Secondary
End point timeframe	Baseline, Weeks 16, 56 and 80
End point values Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Tramadol PR Number of subjects analysed 215 506 502 602 Units: beats per minute arithmetic mean (standard deviation)     Baseline (n =215, 506, 502, 599) 66.4 ( 11.34 ) 67.4 ( 10.34 ) 67.1 ( 10.31 ) 66.9 ( 10.64 )     Change at Week 16 (n =6, 338, 335, 308) 72.3 ( 14.42 ) 68.3 ( 10.00 ) 67.4 ( 10.35 ) 68.8 ( 10.99 )     Change at Week 56 (n =0, 200, 221, 202) 99999 ( 99999 ) 68.6 ( 10.29 ) 68.9 ( 11.02 ) 69.7 ( 11.26 )     Change at Week 80 (n =0, 190, 199, 190) 99999 ( 99999 ) 70.5 ( 10.57 ) 69.3 ( 11.61 ) 70.1 ( 10.98 )
No statistical analyses for this end point

Secondary: Change From Baseline in Heart Rate (as assessed by ECG) at Weeks 16, 56 and 80 Top of page

Secondary: Number of Subjects With Confirmed Orthostatic Hypotension Top of page
End point title	Number of Subjects With Confirmed Orthostatic Hypotension [58]
End point description	Orthostatic hypotension was defined as postural change (supine to standing) that met the following criteria: For systolic BP <=150 mmHg (mean supine): Reduction in systolic BP >=20 mmHg or reduction in diastolic BP >=10 mmHg at the 1 and/or 3 minute standing BP measurements. For systolic BP >150 mmHg (mean supine): Reduction in systolic BP>=30 mmHg or reduction in diastolic BP>=15 mmHg at the 1 and/or 3 minute standing BP measurements. If the 1 minute or 3 minute standing BP in a sequence met the orthostatic hypotension criteria, then that sequence was considered positive. If 2 of 2 or 2 of 3 sequences were positive, then orthostatic hypotension was considered confirmed. The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, ‘Number of subjects analyzed’ signifies subjects analyzed for this endpoint and ‘n’ = subjects who had at least 1 ADA sample for ADA assessment at specified time points. '99999' = signifies that no subjects were evaluable.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
Notes [58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Number of subjects analysed 601 215 503 501 Units: subjects     Baseline (n =601, 215, 503, 501) 2 0 1 0     Week 2 (n =552, 186, 482, 477) 0 1 0 0     Week 4 (n =527, 171, 473, 465) 2 0 2 0     Week 8 (n =485, 151, 452, 445) 1 0 0 0     Week 16 (n =321, 21, 339, 352) 0 0 1 1     Week 24 (n =266, 0, 286, 297) 0 0 0 0     Week 32 (n =228, 0, 241, 255) 0 0 0 0     Week 40 (n =218, 0, 218, 236) 1 0 0 0     Week 48 (n =208, 0, 211, 227) 0 0 1 0     Week 56 (n =204, 0, 202, 223) 0 0 0 1     Week 64 (n =194, 0, 198, 209) 0 0 1 0     Week 80 (n =192, 0, 200, 191) 0 0 1 1
No statistical analyses for this end point

Secondary: Number of Subjects With Confirmed Orthostatic Hypotension Top of page

Secondary: Change From Screening in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80 Top of page
End point title	Change From Screening in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80 [59]
End point description	The SAS is a 12 item (11 for females) questionnaire, from which the total number of symptoms (0-12 for males and 0-11 for females) is calculated. Each positive symptom is rated from 1 (not at all) to 5 (a lot). The total impact score was the sum of all symptom rating scores, with 0 assigned where the subject did not have the particular symptom. The range for the total impact score is 0-60 for males and 0-55 for females, where higher scores indicating higher impact. The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, ‘n’ = subjects who had at least 1 ADA sample for ADA assessment at specified time points. '99999' = signifies that no subjects were evaluable, hence mean and standard deviation not applicable. # signifies number and TSIS signifies Total Symptom Impact Score.
End point type	Secondary
End point timeframe	Screening (up to maximum of 37 days prior to Baseline), Weeks 24, 56 and 80
Notes [59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Number of subjects analysed 602 215 506 502 Units: units on a scale arithmetic mean (standard deviation)     # of symptom reported:Screening(n=602,215,506,502) 0.48 ( 0.74 ) 0.45 ( 0.79 ) 0.43 ( 0.75 ) 0.50 ( 0.82 )     # of symptoms reported:CAW 24 (n= 268,0,287,295) 0.51 ( 1.34 ) 99999 ( 99999 ) 0.32 ( 1.45 ) 0.28 ( 1.37 )     # of symptoms reported: CAW 56(n=204,0,202,223) 0.60 ( 1.49 ) 99999 ( 99999 ) 0.50 ( 1.57 ) 0.30 ( 1.37 )     # of symptoms reported:CAW 80(n=191,0,193,201) 0.45 ( 1.47 ) 99999 ( 99999 ) 0.41 ( 1.38 ) 0.42 ( 1.45 )     TSIS :Screening (n=602,215,506,502) 1.06 ( 1.71 ) 0.93 ( 1.62 ) 0.95 ( 1.69 ) 1.10 ( 1.88 )     TSIS: CAW 24 (n= 268, 0, 287, 295) 1.37 ( 3.68 ) 99999 ( 99999 ) 1.03 ( 4.05 ) 0.76 ( 3.55 )     TSIS: CAW 56 (n= 204, 0, 202, 223) 1.74 ( 3.96 ) 99999 ( 99999 ) 1.49 ( 4.53 ) 0.96 ( 3.87 )     TSIS: CAW 80 (n= 191, 0, 193, 201) 1.43 ( 3.94 ) 99999 ( 99999 ) 1.47 ( 4.26 ) 1.28 ( 4.10 )
No statistical analyses for this end point

Secondary: Change From Screening in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80 Top of page

Secondary: Percentage of Subjects With Adjudicated Joint Safety Outcomes Top of page
End point title	Percentage of Subjects With Adjudicated Joint Safety Outcomes [60]
End point description	Incidence of subjects with any of the joint safety adjudication outcomes of primary osteonecrosis, rapidly progressive OA (type 1 and type 2), subchondral insufficiency fracture (or SPONK), or pathological fracture. The safety population was defined as all subjects treated with tanezumab or placebo SC.
End point type	Secondary
End point timeframe	Baseline up to Week 80
Notes [60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Number of subjects analysed 602 215 506 502 Units: percentage of subjects number (confidence interval 95%)     Composite Joint Safety Endpoint 0.2 (0.0 to 0.9) 0 (0.0 to 1.7) 1.0 (0.3 to 2.3) 2.6 (1.4 to 4.4)     Rapidly Progressive OA 0.2 (0.0 to 0.9) 0 (0.0 to 1.7) 1.0 (0.3 to 2.3) 1.8 (0.8 to 3.4)     Rapidly Progressive OA type 1 0.2 (0.0 to 0.9) 0 (0.0 to 1.7) 1.0 (0.3 to 2.3) 1.4 (0.6 to 2.9)     Rapidly Progressive OA type 2 0 (0.0 to 0.6) 0 (0.0 to 1.7) 0 (0.0 to 0.7) 0.4 (0.0 to 1.4)     Primary Osteonecrosis 0 (0.0 to 0.6) 0 (0.0 to 1.7) 0 (0.0 to 0.7) 0 (0.0 to 0.7)     Pathological Fracture 0 (0.0 to 0.6) 0 (0.0 to 1.7) 0 (0.0 to 0.7) 0 (0.0 to 0.7)     Subchondral Insufficiency Fracture 0 (0.0 to 0.6) 0 (0.0 to 1.7) 0 (0.0 to 0.7) 0.8 (0.2 to 2.0)
No statistical analyses for this end point

Secondary: Percentage of Subjects With Adjudicated Joint Safety Outcomes Top of page

Secondary: Percentage of Subjects With Total Joint Replacements Top of page
End point title	Percentage of Subjects With Total Joint Replacements [61]
End point description	Percentage of subjects who underwent at least one total knee, hip or shoulder joint replacement surgery. The safety population was defined as all subjects treated with tanezumab or placebo SC.
End point type	Secondary
End point timeframe	Baseline up to Week 80
Notes [61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Number of subjects analysed 602 215 506 502 Units: percentage of subjects     number (confidence interval 95%) 0 (0.0 to 0.6) 0 (0.0 to 1.7) 0 (0.0 to 0.7) 1.4 (0.6 to 2.9)
No statistical analyses for this end point

Secondary: Percentage of Subjects With Total Joint Replacements Top of page

Secondary: Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 Top of page
End point title	Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 [62]
End point description	NIS is a standardized instrument used to evaluate subject for signs of peripheral neuropathy. NIS is the sum of scores of 37 items, from both the left and right side, where 24 items scored from 0 (normal) to 4 (paralysis), higher score indicated higher abnormality/impairment and 13 items scored from 0 (normal), 1 (decreased) and 2 (absent), higher score indicated higher impairment. NIS possible overall score ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased impairment. The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, ‘n’ = subjects who had at least 1 ADA sample for ADA assessment at specified time points. '99999' = signifies that no subjects were evaluable, hence mean and standard deviation not applicable.
End point type	Secondary
End point timeframe	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
Notes [62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tramadol Placebo Tanezumab 5 mg Pooled Tanezumab 10 mg Pooled Number of subjects analysed 602 215 506 502 Units: units on a scale arithmetic mean (standard deviation)     Baseline (n =601, 215, 506, 502) 0.78 ( 2.62 ) 1.00 ( 3.55 ) 0.58 ( 2.28 ) 0.86 ( 2.54 )     Change at Week 2 (n =565, 190, 488, 475) -0.15 ( 1.31 ) 0.02 ( 1.29 ) 0.05 ( 1.12 ) -0.08 ( 1.34 )     Change at Week 4 (n =579, 198, 492, 487) -0.16 ( 1.36 ) -0.14 ( 1.35 ) -0.02 ( 0.96 ) -0.17 ( 1.57 )     Change at Week 8 (n =590, 200, 495, 490) 0.08 ( 3.53 ) 0.01 ( 1.97 ) -0.09 ( 1.41 ) -0.17 ( 1.99 )     Change at Week 16 (n =590, 200, 495, 490) 0.02 ( 1.84 ) -0.02 ( 1.91 ) -0.06 ( 1.37 ) -0.06 ( 1.94 )     Change at Week 24 (n =590, 0, 495, 491) 0.03 ( 2.32 ) 99999 ( 99999 ) -0.10 ( 1.58 ) -0.09 ( 1.77 )     Change at Week 32 (n =590, 0, 495, 491) 0.03 ( 1.90 ) 99999 ( 99999 ) -0.14 ( 1.60 ) -0.12 ( 1.73 )     Change at Week 40 (n =590, 0, 495, 491) -0.02 ( 1.97 ) 99999 ( 99999 ) -0.13 ( 1.44 ) -0.13 ( 1.81 )     Change at Week 48 (n =590, 0, 495, 491) 0.00 ( 1.92 ) 99999 ( 99999 ) -0.14 ( 1.33 ) -0.10 ( 1.85 )     Change at Week 56 (n =590, 0, 495, 491) -0.03 ( 1.97 ) 99999 ( 99999 ) -0.16 ( 1.38 ) -0.09 ( 2.07 )     Change at Week 64 (n =590, 0, 495, 491) -0.06 ( 2.03 ) 99999 ( 99999 ) -0.07 ( 2.39 ) -0.09 ( 2.06 )     Change at Week 80 (n =590, 0, 495, 491) -0.07 ( 2.06 ) 99999 ( 99999 ) -0.09 ( 1.94 ) -0.12 ( 2.15 )
No statistical analyses for this end point

Secondary: Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 Top of page

Secondary: Number of Subjects With Anti Tanezumab Antibodies Top of page
End point title	Number of Subjects With Anti Tanezumab Antibodies [63]
End point description	Human serum anti-drug antibody (ADA) samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a semi quantitative enzyme linked immunosorbent assay (ELISA). Subjects listed as having anti-tanezumab antibodies had ADA titer level >=3.32. Less than 3.32 was considered below the limit of quantitation. The safety population was defined as all subjects treated with tanezumab or placebo SC. Here, ‘n’ = subjects who had at least 1 ADA sample for ADA assessment at specified time points. '99999' = signifies that no subjects were evaluable.
End point type	Secondary
End point timeframe	Baseline, Weeks 8, 16, 32, 40, 48, 56, 64 and 80
Notes [63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: No statistical analysis was performed for this endpoint
End point values Tanezumab 5 mg Tramadol Pooled Placebo Number of subjects analysed 407 407 409 Units: subjects     Baseline (n =402, 404, 402) 38 39 45     Week 8 (n = 402, 341, 347) 32 54 37     Week 16 (n =241, 200, 235) 36 46 27     Week 32 (n =166, 181, 0) 32 48 99999     Week 40 (n =0, 0, 0) 99999 99999 99999     Week 48 (n =145, 160, 0) 31 49 99999     Week 56 (n =138, 157, 0) 22 41 99999     Week 64 (n =135, 146, 0) 15 32 99999     Week 80 (n =131, 143, 0) 14 14 99999
No statistical analyses for this end point

Secondary: Number of Subjects With Anti Tanezumab Antibodies Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Baseline up to Week 80
Adverse event reporting additional description	Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event.
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	21.1
Reporting groups
Reporting group title	Tanezumab 5 mg
Reporting group description	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks from Day 1 and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Reporting group title	Tramadol
Reporting group description	Tramadol PR tablet of 100 mg (during baseline to week 4, dose increments by 100 mg was allowed up to a maximum of 300 mg, depending on pain relief or tolerability), once daily and placebo injection matched to tramadol, administered SC once every 8 weeks, from Day 1 up to week 56.
Reporting group title	Placebo
Reporting group description	Placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC, once every 8 weeks from Day 1 (baseline), and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Reporting group title	Tanezumab 10 mg
Reporting group description	Tanezumab (RN624 or PF-04383119) 10 mg injection administered SC once every 8 weeks from Day 1, and placebo tablets matched to tramadol PR, orally, once daily from Day 1 up to week 56.
Serious adverse events Tanezumab 5 mg Tramadol Placebo Tanezumab 10 mg Total subjects affected by serious adverse events      subjects affected / exposed 21 / 506 (4.15%) 25 / 602 (4.15%) 7 / 215 (3.26%) 37 / 502 (7.37%)      number of deaths (all causes) 4 1 1 2      number of deaths resulting from adverse events Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Neoplasm malignant      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Prostate cancer      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Rectal cancer      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Small cell lung cancer      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Lung adenocarcinoma      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 1 / 215 (0.47%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Vascular disorders Aneurysm      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 Aneurysm ruptured      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0 Deep vein thrombosis      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Aortic aneurysm      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 1 / 215 (0.47%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Pregnancy, puerperium and perinatal conditions Foetal death      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Unintended pregnancy      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 General disorders and administration site conditions Chest pain      subjects affected / exposed 1 / 506 (0.20%) 1 / 602 (0.17%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 1 0 / 1 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Non-cardiac chest pain      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Immune system disorders Drug hypersensitivity      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 1 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Hypersensitivity      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Reproductive system and breast disorders Prostatitis      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Respiratory, thoracic and mediastinal disorders Acute respiratory failure      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Chronic obstructive pulmonary disease      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Pneumonia aspiration      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Pneumothorax      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 2 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Pulmonary hypertension      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Respiratory failure      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Psychiatric disorders Depression      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Major depression      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Mental status changes      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Depression suicidal      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 1 / 215 (0.47%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Injury, poisoning and procedural complications Ankle fracture      subjects affected / exposed 1 / 506 (0.20%) 1 / 602 (0.17%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 1 0 / 1 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Ligament sprain      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Limb injury      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Meniscus injury      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Procedural nausea      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Road traffic accident      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 1 / 215 (0.47%) 2 / 502 (0.40%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 2      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1 Spinal compression fracture      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Toxicity to various agents      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1 Urinary retention postoperative      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 1 / 215 (0.47%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Cardiac disorders Atrial fibrillation      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Cardiac failure      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 1 / 215 (0.47%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 Cardiac failure congestive      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Coronary artery disease      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Myocardial infarction      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 Palpitations      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Supraventricular tachycardia      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Nervous system disorders Carpal tunnel syndrome      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Guillain-Barre syndrome      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Lumbar radiculopathy      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 2 / 502 (0.40%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 2      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Seizure      subjects affected / exposed 1 / 506 (0.20%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Syncope      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Transient ischaemic attack      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Ear and labyrinth disorders Vertigo      subjects affected / exposed 0 / 506 (0.00%) 2 / 602 (0.33%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 2 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Deafness neurosensory      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 1 / 215 (0.47%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Eye disorders Pupils unequal      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Uveitis      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Gastrointestinal disorders Abdominal pain upper      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Anal fistula      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Colitis      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Colitis ischaemic      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Gastrointestinal haemorrhage      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Hiatus hernia      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Large intestine perforation      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Oesophageal rupture      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Pancreatitis      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Hepatobiliary disorders Biliary dyskinesia      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Cholecystitis      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Cholelithiasis      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Renal and urinary disorders Acute kidney injury      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Nephrolithiasis      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Ureterolithiasis      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Urinary incontinence      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Musculoskeletal and connective tissue disorders Back pain      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Intervertebral disc compression      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Intervertebral disc protrusion      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Muscular weakness      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Osteoarthritis      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 3 / 502 (0.60%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 2 / 3      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Rapidly progressive osteoarthritis      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 5 / 502 (1.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 4 / 6      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Rotator cuff syndrome      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 3 / 502 (0.60%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 3      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Subchondral insufficiency fracture      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Infections and infestations Abdominal abscess      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Amoebic colitis      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Arthritis infective      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Influenza      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 Pyelonephritis      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Sepsis      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Staphylococcal infection      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Staphylococcal sepsis      subjects affected / exposed 1 / 506 (0.20%) 0 / 602 (0.00%) 0 / 215 (0.00%) 0 / 502 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Tooth abscess      subjects affected / exposed 0 / 506 (0.00%) 0 / 602 (0.00%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 Urinary tract infection      subjects affected / exposed 0 / 506 (0.00%) 1 / 602 (0.17%) 0 / 215 (0.00%) 1 / 502 (0.20%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Tanezumab 5 mg Tramadol Placebo Tanezumab 10 mg Total subjects affected by non serious adverse events      subjects affected / exposed 201 / 506 (39.72%) 275 / 602 (45.68%) 65 / 215 (30.23%) 203 / 502 (40.44%) Injury, poisoning and procedural complications Fall      subjects affected / exposed 26 / 506 (5.14%) 18 / 602 (2.99%) 4 / 215 (1.86%) 20 / 502 (3.98%)      occurrences all number 31 20 4 22 Nervous system disorders Dizziness      subjects affected / exposed 12 / 506 (2.37%) 44 / 602 (7.31%) 4 / 215 (1.86%) 11 / 502 (2.19%)      occurrences all number 12 47 4 12 Headache      subjects affected / exposed 39 / 506 (7.71%) 50 / 602 (8.31%) 13 / 215 (6.05%) 36 / 502 (7.17%)      occurrences all number 48 62 20 39 Somnolence      subjects affected / exposed 5 / 506 (0.99%) 33 / 602 (5.48%) 6 / 215 (2.79%) 7 / 502 (1.39%)      occurrences all number 5 36 6 7 Gastrointestinal disorders Constipation      subjects affected / exposed 9 / 506 (1.78%) 52 / 602 (8.64%) 3 / 215 (1.40%) 12 / 502 (2.39%)      occurrences all number 10 53 3 13 Nausea      subjects affected / exposed 16 / 506 (3.16%) 78 / 602 (12.96%) 5 / 215 (2.33%) 16 / 502 (3.19%)      occurrences all number 21 82 5 17 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 68 / 506 (13.44%) 65 / 602 (10.80%) 22 / 215 (10.23%) 71 / 502 (14.14%)      occurrences all number 87 83 39 97 Back pain      subjects affected / exposed 39 / 506 (7.71%) 33 / 602 (5.48%) 15 / 215 (6.98%) 33 / 502 (6.57%)      occurrences all number 49 40 16 36 Musculoskeletal pain      subjects affected / exposed 36 / 506 (7.11%) 31 / 602 (5.15%) 12 / 215 (5.58%) 27 / 502 (5.38%)      occurrences all number 37 36 12 33 Infections and infestations Nasopharyngitis      subjects affected / exposed 31 / 506 (6.13%) 37 / 602 (6.15%) 11 / 215 (5.12%) 32 / 502 (6.37%)      occurrences all number 34 42 12 39 Upper respiratory tract infection      subjects affected / exposed 25 / 506 (4.94%) 30 / 602 (4.98%) 4 / 215 (1.86%) 34 / 502 (6.77%)      occurrences all number 28 35 4 37

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Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
27 Jul 2015	Clarification to the prohibited medications in Section 5.8.1 and Appendix 4, to specify that opioids analgesics are prohibited through Week 64.
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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