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    Clinical Trial Results:
    A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of The Analgesic Efficacy and Safety of The Subcutaneous Administration of Tanezumab (Pf-04383119) In Subjects With Cancer Pain Predominantly Due to Bone Metastasis Receiving Background Opioid Therapy

    Summary
    EudraCT number
    		 2013-002223-42
    Trial protocol
    		 AT   CZ   GB   PL   ES   SK   HU   RO   FR   DE  
    Global end of trial date
    25 Jun 2021

    Results information
    Results version number
    		 v2(current)
    This version publication date
    29 Dec 2022
    First version publication date
    09 Jul 2022
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A4091061
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02609828
    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 8007181021, 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)
    No
    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
    21 Oct 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jun 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Demonstrate superior analgesic efficacy of tanezumab 20 mg SC versus matching placebo SC at Week 8 in subjects, with cancer pain predominantly due to bone metastasis, receiving background opioid therapy.
    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 trials subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Oct 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 1
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    Brazil: 7
    Country: Number of subjects enrolled
    Chile: 6
    Country: Number of subjects enrolled
    China: 17
    Country: Number of subjects enrolled
    Czechia: 1
    Country: Number of subjects enrolled
    Hungary: 4
    Country: Number of subjects enrolled
    Japan: 11
    Country: Number of subjects enrolled
    Korea, Republic of: 7
    Country: Number of subjects enrolled
    Poland: 50
    Country: Number of subjects enrolled
    Romania: 22
    Country: Number of subjects enrolled
    Slovakia: 17
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    United Kingdom: 5
    Worldwide total number of subjects
    155
    EEA total number of subjects
    100
    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)
    96
    From 65 to 84 years
    59
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects with cancer pain mainly due to bone metastasis,receiving background opioid therapy,randomised to 3 treatment arms:tanezumab20milligrams(mg),10mg,placebo. After study start,10mg arm discontinued(protocol amendment3)no new subjects enrolled in this arm. Existing subjects in arm received 20 mg for remaining doses and included in10/20mg arm.

    Pre-assignment
    Screening details
    		 Total 325 subjects signed the inform consent form (ICF). Out of which 158 subjects were screen failures, and 11 subjects were screened but not enrolled and randomised into the study. Total of 156 subjects were enrolled and randomised into the study and assigned to study treatments.

    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
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects received placebo matched to tanezumab subcutaneous (SC) once every 8 weeks for 24 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo (Tanezumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matched to Tanezumab was administered via SC injection once every 8 weeks for 24 weeks. All subjects received 1 mL of study medication administered as a SC injection. Administered in the abdomen or anterior aspect of the thigh.

    Arm title
    		 Tanezumab 10 mg
    Arm description
    		 Subjects in this discontinued treatment arm, received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and completed their treatment before the amendment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tanezumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received Tanezumab 10 mg/mL, SC once every 8 weeks before protocol amendment 3 and completed their treatment before the amendment. Administered in the abdomen or anterior aspect of the thigh.

    Arm title
    		 Tanezumab 10/20 mg
    Arm description
    		 Subjects in this treatment group had received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and after the amendment they continued remaining treatment with tanezumab 20 mg SC once every 8 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tanezumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received tanezumab 10 mg/ml SC, once every 8 weeks before protocol amendment 3 and after the amendment they continued remaining treatment with tanezumab 20 mg SC once every 8 weeks. Administered in the abdomen or anterior aspect of the thigh.

    Arm title
    		 Tanezumab 20 mg
    Arm description
    		 Subjects received tanezumab 20 mg SC once every 8 weeks for 24 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tanezumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received tanezumab 20 mg/ml SC once every 8 weeks for 24 weeks. Administered in the abdomen or anterior aspect of the thigh.

    Number of subjects in period 1
    		Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Started
    73
    9
    1
    72
    Treated
    73
    9
    1
    72
    Completed
    31
    5
    0
    29
    Not completed
    42
    4
    1
    43
         Consent withdrawn by subject
    12
    1
    -
    10
         Adverse event, non-fatal
    8
    1
    -
    6
         Death
    15
    1
    1
    19
         Unspecified
    3
    -
    -
    6
         Lost to follow-up
    -
    -
    -
    1
         Insufficient clinical response
    2
    1
    -
    -
         Protocol deviation
    2
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received placebo matched to tanezumab subcutaneous (SC) once every 8 weeks for 24 weeks.

    Reporting group title
    Tanezumab 10 mg
    Reporting group description
    		 Subjects in this discontinued treatment arm, received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and completed their treatment before the amendment.

    Reporting group title
    Tanezumab 10/20 mg
    Reporting group description
    		 Subjects in this treatment group had received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and after the amendment they continued remaining treatment with tanezumab 20 mg SC once every 8 weeks.

    Reporting group title
    Tanezumab 20 mg
    Reporting group description
    		 Subjects received tanezumab 20 mg SC once every 8 weeks for 24 weeks.

    Reporting group values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg Total
    Number of subjects
    		 73 9 1 72 155
    Age Categorical
    Units: Subjects
        >=18 to < 45 years
    		 10 1 0 3 14
        >=45 to <65 years
    		 44 4 1 33 82
        >=65 years
    		 19 4 0 36 59
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.0 ( 11.1 ) 61.6 ( 9.9 ) 58.0 ( 99999 ) 63.5 ( 10.1 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 39 4 0 26 69
        Male
    		 34 5 1 46 86
    Race
    Units: Subjects
        Asian
    		 16 3 0 16 35
        Black or African American
    		 1 0 0 1 2
        White
    		 56 6 1 55 118
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 10 0 0 5 15
        Not Hispanic or Latino
    		 63 9 1 67 140

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received placebo matched to tanezumab subcutaneous (SC) once every 8 weeks for 24 weeks.

    Reporting group title
    Tanezumab 10 mg
    Reporting group description
    		 Subjects in this discontinued treatment arm, received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and completed their treatment before the amendment.

    Reporting group title
    Tanezumab 10/20 mg
    Reporting group description
    		 Subjects in this treatment group had received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and after the amendment they continued remaining treatment with tanezumab 20 mg SC once every 8 weeks.

    Reporting group title
    Tanezumab 20 mg
    Reporting group description
    		 Subjects received tanezumab 20 mg SC once every 8 weeks for 24 weeks.

    Primary: Change From Baseline in the Daily Average Pain Intensity Numerical Rating Score (NRS) in the Index Bone Metastasis Cancer Pain Site at Week 8

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    End point title
    		 Change From Baseline in the Daily Average Pain Intensity Numerical Rating Score (NRS) in the Index Bone Metastasis Cancer Pain Site at Week 8
    End point description
    Daily average(avg)pain intensity in index bone metastasis cancer pain site assessed by subjects:11point pain intensity NRS.Range:0(no pain)to10(worst possible pain).Higher scores:more severity of pain.Subjects recorded pain during past 24hours from 0to10 on interactive response technology(IRT)diaries.Baseline daily avg pain intensity value:mean of daily avg pain intensity NRS scores during baseline assessment period(up to 5 days prior dosing)prior to randomisation.Week(wk)8 daily avg pain intensity value:mean of daily avg pain intensity NRS scores recorded for 7 days prior to wk 8.Efficacy data from subjects originally randomised to tanezumab 10mg arm not included in analyses of efficacy as pre-specified in protocol.So,summarised data is not reported for tanezumab 10mg and 10/20mg arms.99999=summarised data not available.Individual values at wk 8 for 10mg: -3,-1.8,-0.6,-3.65,-2.4,-3,-1,-2; for10/20mg: -0.48 respectively.Number of subjects analysed(N)=subjects evaluable for endpoint.
    End point type
    Primary
    End point timeframe
    Baseline, Week (wk) 8
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    8
    1
    72
    Units: Units on a scale
        least squares mean (standard error)
    -1.25 ( 0.35 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.03 ( 0.35 )
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 8: Analysis of covariance (ANCOVA) model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0381
    Method
    		 ANCOVA
    Parameter type
    		 Differences in least square (LS) mean
    Point estimate
    -0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.52
         upper limit
    		 -0.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.37

    Secondary: Change From Baseline in the Daily Average Pain Intensity NRS score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 12, 16 and 24

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    End point title
    		 Change From Baseline in the Daily Average Pain Intensity NRS score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 12, 16 and 24
    End point description
    Daily avg pain intensity in index bone metastasis cancer pain site assessed by subjects:11 point pain intensity NRS.Range:0(no pain)to10(worst possible pain).Higher score:more severity of pain.Subjects noted pain:past 24hours(0to10)onIRT diaries.Baseline daily avg pain intensity value:mean of daily avg pain intensityNRS score during baseline assessment period(upto5days prior to dosing)prior to randomisation.Wk1,2,4,6,12,16,24daily avg pain intensity value:mean of daily avg pain intensityNRS score for7days prior to each wk.99999=summarised data not available.Individual values at specified wk for10mg:0,0.2,-2.42,-0.45,-2.08,-0.4,-,0.14,0, 0,-0.08,-3.4,-0.45,-2.3,-0.4,0,0,0,-0.14,-0.5,-2,-0.74,-4.08,-1.4,0,-0.71,-1.14,-2,-0.94,-0.88,-2.94,-1.97,-3,-1,-2,-3.76,-1.8,-2.5,0.9,-2.22,-2.4,-1.75,-0.5,-2.75,-4,-2.3,-1.3,-1.9,-1,-1.33,-3,-4,-1.8,-2.55,-1.15,-3,-3;10/20mg:-0.62,-1.2,-0.91,-0.62,-2.2,respectively.99999=no subjects. Here,’n’=subjects evaluable at specific time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 2, 4, 6, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Units on a scale
    least squares mean (standard error)
        Change at Week 1 (n=73,9,1,72)
    -0.40 ( 0.16 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.76 ( 0.17 )
        Change at Week 2 (n=73,9,1,72)
    -0.72 ( 0.23 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.38 ( 0.23 )
        Change at Week 4 (n=73,9,1,72)
    -1.03 ( 0.29 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.77 ( 0.31 )
        Change at Week 6 (n=73,8,1,72)
    -1.17 ( 0.33 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.04 ( 0.34 )
        Change at Week 12 (n=73,9,1,72)
    -1.51 ( 0.37 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.10 ( 0.37 )
        Change at Week 16 (n=73,7,1,72)
    -1.37 ( 0.40 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.92 ( 0.42 )
        Change at Week 24 (n=73,6,1,72)
    -1.04 ( 0.44 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.62 ( 0.43 )
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 1: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0497
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.72
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 2: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0092
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.16
         upper limit
    		 -0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 4: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0218
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.37
         upper limit
    		 -0.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 6: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0154
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.58
         upper limit
    		 -0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 12: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1289
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.36
         upper limit
    		 0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.39
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 16: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.211
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.43
         upper limit
    		 0.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.44
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 24: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2049
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.49
         upper limit
    		 0.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.46

    Secondary: Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    Daily worst pain intensity assessed by subjects:11point pain intensity NRS.Range:0(no pain)to10(worst possible pain).Higher scores:more severe pain.Subjects noted pain:past 24hours(0to10)onIRT diaries.Baseline daily worst pain intensity:mean of daily worst pain intensityNRS score during baseline assessment period(upto 5days prior to dosing)before randomisation.Wk1,2,4,6,8,12,16,24 daily worst pain intensity value:mean of daily worst pain intensity NRS scores noted for7days prior to each wk.99999=summarised data not available.Individual values:each wk:10mg:0.4,0.2,-2.85,-0.4,-1.8,-0.4,0,0.45,0,0.4,-0.08,-4,-0.25,-2.37,-0.4,0,0.6,0,-0.02,-0.51,-1.85,-0.4,-4.08,-1.4,0,0.02,-1.14,-2.74,-0.94,-0.54,-2.94,-1.97,-3,-0.4,-2,-4.6,-1.51,-0.4,-3.65,-2.4,-3,-0.25,-2, -4.63,-1.8,-3.5,0.6,-2.22,-2.4,-1.75,0.1,-2.75,-4.6,-2.3,-1.3,-1.9,-1,-0.73,-3,-4.9,-1.8,-2.55,-1.15,-5.4,-3;10/20 mg:-1.42,-1.57,-1.42,-1.14,-0.85-2.99999=no subjects. Here,’n’=subjects evaluable at specific time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Units on a scale
    least squares mean (standard error)
        Change at Week 1 (n=73,9,1,72)
    -0.52 ( 0.18 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.84 ( 0.19 )
        Change at Week 2 (n=73,9,1,72)
    -0.74 ( 0.25 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.47 ( 0.25 )
        Change at Week 4 (n=73,9,1,72)
    -1.14 ( 0.30 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.88 ( 0.31 )
        Change at Week 6 (n=73,8,1,72)
    -1.20 ( 0.33 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.08 ( 0.34 )
        Change at Week 8 (n=73,9,1,72)
    -1.38 ( 0.36 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.14 ( 0.37 )
        Change at Week 12 (n=73,9,1,72)
    -1.53 ( 0.36 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.25 ( 0.38 )
        Change at Week 16 (n=73,7,1,72)
    -1.32 ( 0.44 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.06 ( 0.43 )
        Change at Week 24 (n=73,6,1,72)
    -1.10 ( 0.44 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.90 ( 0.45 )
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 1: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1103
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.73
         upper limit
    		 0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 4:ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0236
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.39
         upper limit
    		 -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 2: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0084
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.26
         upper limit
    		 -0.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.27
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 6: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0155
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.59
         upper limit
    		 -0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 8: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0505
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.52
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.38
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 12: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0761
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.52
         upper limit
    		 0.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 16: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1263
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 0.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.48
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 24: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1051
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.76
         upper limit
    		 0.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.49

    Secondary: Change From Baseline in the Weekly Average Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Change From Baseline in the Weekly Average Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    Weekly avg pain intensity in non-index cancer pain site(most painful cancer pain sites other than index bone metastasis cancer pain site) was assessed by subjects on NRS ranging 0=no pain to 10=worst possible pain, higher scores: more severity of pain. Subjects described weekly pain at painful site, scores 0 to 10 on IRT diaries. Baseline weekly avg pain intensity: weekly avg pain intensity NRS score recorded on any day during baseline assessment period (5 days prior to dosing). Wk 1, 2, 4, 6, 8, 12, 16 and 24 weekly avg pain intensity value: weekly avg pain intensity NRS scores recorded on any day from span of 7 days prior to specified wk. mITT set analyzed. Multiple imputation applied. 99999=summarised data not available. Individual values at wk 1,2,4,6,8,12,16 and 24, for 10 mg: 1,0.5,-1,0,-1,-3,-2,-3,-2,-1.375,-2,-1.375,-2; for 10/20 mg: 0,1.5,0.5,0,-2,-1 respectively. 99999=no subjects analysed. N:subjects evaluable for endpoint. n:subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    23
    2
    1
    32
    Units: Units on a scale
    least squares mean (standard error)
        Change at Week 1 (n=23, 1, 1, 32)
    -0.64 ( 0.42 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.14 ( 0.35 )
        Change at Week 2 (n=23, 1, 1, 32)
    -0.96 ( 0.54 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.81 ( 0.47 )
        Change at Week 4 (n=23, 2, 1, 32)
    -1.42 ( 0.59 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.22 ( 0.52 )
        Change at Week 6 (n=23, 2, 1, 32)
    -1.76 ( 0.65 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.24 ( 0.56 )
        Change at Week 8 (n=23, 2, 1, 32)
    -1.79 ( 0.70 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.34 ( 0.62 )
        Change at Week 12 (n=23, 2, 1, 32)
    -1.64 ( 0.59 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.14 ( 0.53 )
        Change at Week 16 (n=23, 2, 0, 32)
    -1.06 ( 0.71 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.27 ( 0.60 )
        Change at Week 24 (n=23, 1, 0, 32)
    -0.87 ( 0.68 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.92 ( 0.59 )
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 1: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3003
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.47
         upper limit
    		 0.47
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.48
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 2: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1603
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.03
         upper limit
    		 0.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.59
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 4: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2298
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.13
         upper limit
    		 0.53
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 6: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5054
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.93
         upper limit
    		 0.97
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 8: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4793
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 1.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.77
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 12: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4496
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.83
         upper limit
    		 0.83
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 16: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1263
    Method
    		 ANCOVA
    Parameter type
    		 Difference in least square LS mean
    Point estimate
    -1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.77
         upper limit
    		 0.36
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.77
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 24: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.162
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.54
         upper limit
    		 0.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.73

    Secondary: Change From Baseline in the Weekly Worst Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Change From Baseline in the Weekly Worst Pain Intensity NRS Score in Non-Index Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    Weekly worst pain intensity in non-index cancer pain site(most painful cancer pain sites other than index bone metastasis cancer pain site)assessed by subjects on NRS ranging 0=no pain to 10=worst possible pain, higher scores: more severe pain. Subjects described their weekly worst pain at painful site from 0 to 10. Baseline weekly worst pain intensity: weekly worst pain intensity NRS score recorded on any day during baseline assessment period (5 days prior to dosing). Wk 1, 2, 4, 6, 8, 12, 16 and 24 weekly worst pain intensity value was weekly worst pain intensity NRS scores recorded on any day in 7 days prior to specified wk. mITT set analyzed. Multiple imputation applied. 99999: summarised data not available. Individual values at Wk 1,2,4,6,8,12,16 and 24, for 10 mg: 1, 0.5, -1, 0,-1,-3,-2,-3, -2,-1.75, -2 -1.625,-2; for 10/20 mg: -0.5, 0.5,0 0.5,-1 and -0.5 respectively. 99999:no subjects analysed. N:subjects evaluable for endpoint. n:subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    23
    2
    1
    32
    Units: Units on a scale
    least squares mean (standard error)
        Change at Week 1 (n=23, 1, 1, 32)
    -0.43 ( 0.50 )
    99999 ( 99999 )
    99999 ( 99999 )
    -1.50 ( 0.42 )
        Change at Week 2 (n=23, 1, 1, 32)
    -0.34 ( 0.59 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.30 ( 0.51 )
        Change at Week 4 (n=23, 2, 1, 32)
    -1.18 ( 0.66 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.62 ( 0.56 )
        Change at Week 6 (n=23, 2, 1, 32)
    -1.62 ( 0.73 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.50 ( 0.61 )
        Change at Week 8 (n=23, 2, 1, 32)
    -1.77 ( 0.74 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.54 ( 0.64 )
        Change at Week 12 (n=23, 2, 1, 32)
    -1.36 ( 0.68 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.56 ( 0.57 )
        Change at Week 16 (n=23, 2, 0, 32)
    -0.85 ( 0.82 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.75 ( 0.66 )
        Change at Week 24 (n=23, 1, 0, 32)
    -0.73 ( 0.79 )
    99999 ( 99999 )
    99999 ( 99999 )
    -2.35 ( 0.67 )
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 1: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0575
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.17
         upper limit
    		 0.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.54
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 2: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0031
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.22
         upper limit
    		 -0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.62
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 4: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.041
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.82
         upper limit
    		 -0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 6: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2598
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.44
         upper limit
    		 0.68
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.77
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 8: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3426
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.38
         upper limit
    		 0.85
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.8
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 12: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1034
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.65
         upper limit
    		 0.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 16: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.029
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 -0.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.84
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 24: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the non-index cancer pain sites and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.06
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -1.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.31
         upper limit
    		 0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.83

    Secondary: Change From Baseline in the Daily Average Pain Intensity NRS score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Change From Baseline in the Daily Average Pain Intensity NRS score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    Daily avg pain intensity in the non-index visceral cancer pain site was assessed by participants on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The subjects described their pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline is defined as the mean average daily pain intensity NRS score during the baseline assessment period prior to randomisation. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value is the mean of the daily avg pain intensity scores for the 7 days prior to each specified week. Subject with non-index visceral cancer pain sites were less than 10, hence data was not collected and analysis was not performed for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    0 [1]
    0 [2]
    0 [3]
    0 [4]
    Units: Units on a scale
        least squares mean (standard error)
    ( )
    ( )
    ( )
    ( )
    Notes
    [1] - Non-index visceral cancer pain sites subject= <10,so,data not collected,analysed for the end point.
    [2] - Non-index visceral cancer pain sites subject= <10,so,data not collected,analysed for the end point.
    [3] - Non-index visceral cancer pain sites subject= <10,so,data not collected,analysed for the end point.
    [4] - Non-index visceral cancer pain sites subject= <10,so,data not collected,analysed for the end point.
    No statistical analyses for this end point

    Secondary: Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Change From Baseline in the Daily Worst Pain Intensity NRS Score in the Non-Index Visceral Cancer Pain Sites at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    Daily worst pain intensity in the index bone metastasis cancer pain site was assessed by subjects on an 11 point pain intensity NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores signified more severity of pain. The subjects recorded their daily worst pain at the painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Baseline pain intensity value was mean of the daily worst pain intensity NRS scores during the baseline assessment period prior to randomisation. Baseline assessment period was up to 5 days prior to dosing. The Weeks 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value is the mean of the daily worst pain intensity scores for the 7 days prior to the each specified week. Subject with non-index visceral cancer pain sites were less than 10, hence data was not collected and analysis was not performed for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    0 [5]
    0 [6]
    0 [7]
    0 [8]
    Units: Units on a scale
        least squares mean (standard error)
    ( )
    ( )
    ( )
    ( )
    Notes
    [5] - Non-index visceral cancer pain sites subject= <10,so,data not collected,analysed for the end point.
    [6] - Non-index visceral cancer pain sites subject= <10,so,data not collected,analysed for the end point.
    [7] - Non-index visceral cancer pain sites subject= <10,so,data not collected,analysed for the end point.
    [8] - Non-index visceral cancer pain sites subject= <10,so,data not collected,analysed for the end point.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Cumulative Reduction of >=30, 50, 70 and 90 Percent (%) From Baseline in Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Number of Subjects With Cumulative Reduction of >=30, 50, 70 and 90 Percent (%) From Baseline in Daily Average Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    Daily avg pain intensity in index bone metastasis cancer pain site assessed by subjects:11 point pain intensity NRS. Range:0(no pain) to 10(worst possible pain),higher scores=more severe pain. Subjects recorded daily average pain at painful site during the past 24 hours by choosing the appropriate number from 0 to 10 on IRT diaries. Wk 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value=mean of the daily avg pain intensity NRS scores for the 7 days prior to each week. Number of subjects with cumulative reduction of >=30,50,70,90 % in daily avg pain intensity NRS score in the index bone metastasis cancer pain site from Baseline to Wk 1, 2, 4, 6, 8, 12, 16 and 24 were reported. Subjects might be reported more than once in the specified rows for a time point. Rows with only non-zero data for cumulative reduction at specified time points, for at least 1 reporting arm, are reported below. Here, ‘N’: subjects evaluable for this end point and ‘n’: subjects evaluable at specific time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    71
    Units: Subjects
        Week 1: Reduction of >=30% (n=73,9,1,71)
    8
    2
    0
    9
        Week 1: Reduction of >=50% (n=73,9,1,71)
    4
    0
    0
    4
        Week 1: Reduction of >=70% (n=73,9,1,71)
    0
    0
    0
    1
        Week 2: Reduction of >=30% (n=73,9,1,71)
    11
    2
    0
    18
        Week 2: Reduction of >=50% (n=73,9,1,71)
    3
    1
    0
    13
        Week 2: Reduction of >=70%(n=73,9,1,71)
    0
    0
    0
    4
        Week 2: Reduction of >=90%(n=73,9,1,71)
    0
    0
    0
    2
        Week 4: Reduction of >=30%(n=73,9,1,71)
    18
    2
    0
    25
        Week 4: Reduction of >=50%(n=73,9,1,71)
    6
    1
    0
    16
        Week 4: Reduction of >=70%(n=73,9,1,71)
    2
    1
    0
    9
        Week 4: Reduction of >=90%(n=73,9,1,71)
    0
    0
    0
    3
        Week 6: Reduction of >=30%(n=73,9,1,71)
    20
    5
    0
    30
        Week 6: Reduction of >=50%(n=73,9,1,71)
    6
    1
    0
    19
        Week 6: Reduction of >=70% (n=73,8,1,71)
    2
    0
    0
    10
        Week 6: Reduction of >=90%(n=73,9,1,71)
    0
    0
    0
    3
        Week 8: Reduction of >=30% (n=73,8,1,71)
    19
    5
    0
    28
        Week 8: Reduction of >=50%(n=73,9,1,71)
    9
    2
    0
    18
        Week 8: Reduction of >=70%(n=73,9,1,71)
    3
    0
    0
    9
        Week 8: Reduction of >=90%(n=73,9,1,71)
    1
    0
    0
    5
        Week 12: Reduction of >=30%(n=73,9,1,71)
    21
    5
    1
    32
        Week 12: Reduction of >=50%(n=73,9,1,71)
    12
    2
    0
    21
        Week 12: Reduction of >=70%(n=73,9,1,71)
    6
    1
    0
    10
        Week 12: Reduction of >=90%(n=73,9,1,71)
    2
    0
    0
    5
        Week 16: Reduction of >=30% (n=73,7,1,71)
    17
    2
    0
    27
        Week 16: Reduction of >=50%(n=73,9,1,71)
    12
    2
    0
    19
        Week 16: Reduction of >=70%(n=73,9,1,71)
    7
    1
    0
    12
        Week 16: Reduction of >=90%(n=73,9,1,71)
    5
    0
    0
    5
        Week 24: Reduction of >=30% (n=73,6,1,71)
    16
    4
    0
    27
        Week 24: Reduction of >=50%(n=73,9,1,71)
    10
    3
    0
    19
        Week 24: Reduction of >=70%(n=73,9,1,71)
    5
    2
    0
    11
        Week 24: Reduction of >=90%(n=73,9,1,71)
    3
    1
    0
    4
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 1 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8054
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 3.18
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 1 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9565
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 1 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9292
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 3.98
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1429
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 4.36
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9489
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.945
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.014
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.4
         upper limit
    		 19.31
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1932
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 3.39
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0254
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.15
         upper limit
    		 8.74
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0455
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 24.16
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9464
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 6 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0969
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 3.72
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 6 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0043
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.58
         upper limit
    		 11.74
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 6 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0352
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.13
         upper limit
    		 26.75
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 6 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9464
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1471
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 3.52
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0993
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 12.83
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0405
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 6.22
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1726
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 43.64
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 12 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0918
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 3.74
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 12 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0704
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 4.82
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 12 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3569
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 5.01
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 12 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3062
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 13.79
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1058
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 3.85
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1571
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 4.14
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8867
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 3.46
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2454
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 5.24
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0689
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 4.21
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0568
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 5.44
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1268
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 7.46
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7971
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 6

    Secondary: Number of Subjects With Reduction of >=30, 50, 70 and 90% From Baseline in Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Number of Subjects With Reduction of >=30, 50, 70 and 90% From Baseline in Daily Worst Pain Intensity NRS Score in the Index Bone Metastasis Cancer Pain Site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    Daily worst pain intensity in index bone metastasis cancer pain site assessed by subjects:11 point pain intensity NRS. Range:0(no pain) to10(worst possible pain), higher scores = more severe pain. Subjects recorded daily worst pain at painful site during past 24 hours by choosing appropriate number from 0 to 10 on IRT diaries. Wk 1, 2, 4, 6, 8, 12, 16 and 24 pain intensity value = mean of the daily worst pain intensity NRS scores for the 7 days prior to each wk. Number of subjects with cumulative reduction of >= 30,50,70,90 % in daily worst pain intensity NRS score in the index bone metastasis cancer pain site from Baseline to Wk 1, 2, 4, 6, 8, 12, 16 and 24 were reported. Subjects might be reported more than once in the specified rows for a time point. Rows with only non-zero data for cumulative reduction at specified time points, for at least 1 reporting arm, are reported below. Here, ‘N’: subjects evaluable for this end point and ‘n’: subjects evaluable at specific time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    0 [9]
    71
    Units: Subjects
        Week 1: Reduction of >=30%
    7
    2
    9
        Week 1: Reduction of >=50%
    1
    0
    3
        Week 1: Reduction of >=70%
    0
    0
    2
        Week 1: Reduction of >=90%
    0
    0
    0
        Week 2: Reduction of >=30%
    9
    2
    17
        Week 2: Reduction of >=50%
    2
    1
    8
        Week 2: Reduction of >=70%
    0
    0
    5
        Week 2: Reduction of >=90%
    0
    0
    2
        Week 4: Reduction of >=30%
    12
    1
    21
        Week 4: Reduction of >=50%
    5
    1
    14
        Week 4: Reduction of >=70%
    0
    1
    6
        Week 4: Reduction of >=90%
    0
    0
    2
        Week 6: Reduction of >=30%
    13
    4
    26
        Week 6: Reduction of >=50%
    4
    1
    14
        Week 6: Reduction of >=70%
    2
    0
    7
        Week 6: Reduction of >=90%
    0
    0
    2
        Week 8: Reduction of >=30%
    14
    5
    24
        Week 8: Reduction of >=50%
    7
    2
    16
        Week 8: Reduction of >=70%
    2
    0
    8
        Week 8: Reduction of >=90%
    2
    0
    2
        Week 12: Reduction of >=30%
    16
    5
    24
        Week 12: Reduction of >=50%
    8
    2
    16
        Week 12: Reduction of >=70%
    5
    1
    7
        Week 12: Reduction of >=90%
    2
    0
    4
        Week 16: Reduction of >=30%
    11
    2
    24
        Week 16: Reduction of >=50%
    9
    2
    18
        Week 16: Reduction of >=70%
    7
    0
    11
        Week 16: Reduction of >=90%
    3
    0
    3
        Week 24: Reduction of >=30%
    11
    4
    25
        Week 24: Reduction of >=50%
    9
    3
    18
        Week 24: Reduction of >=70%
    4
    2
    9
        Week 24: Reduction of >=90%
    2
    0
    3
    Notes
    [9] - No subjects met criteria for data collection and analysis for 10/20 mg for this end point.
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 1 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6658
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 3.7
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 1 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3443
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 31.35
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 1 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9527
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0757
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 5.5
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0659
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 22.42
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.938
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9493
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0914
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 4.59
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0359
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.08
         upper limit
    		 9.61
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9538
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9493
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 6 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0143
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.22
         upper limit
    		 5.8
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 6 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0176
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.28
         upper limit
    		 13.74
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 6 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1298
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 18.06
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 6 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9493
    Method
    		 Regression, Logistic
    Confidence interval
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0527
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 4.67
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0994
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 19.76
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0457
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 7.12
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6977
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.07
         upper limit
    		 5.86
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 12 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.146
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 3.75
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 12 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0742
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 6.01
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 12 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5565
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 4.91
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 12 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5623
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 10.35
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0116
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.27
         upper limit
    		 6.47
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0615
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 5.7
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9946
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 5.33
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3316
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 4.8
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Reduction >=30%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0083
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.33
         upper limit
    		 6.76
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Reduction >=50%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0513
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 5.88
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Reduction >=70%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1528
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 8.58
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Reduction >=90%: Logistic regression model included baseline average pain intensity at the index bone metastasis cancer pain site, baseline worst pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7251
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.21
         upper limit
    		 9.65

    Secondary: Change From Baseline in Subjects Global Assessment of Cancer Pain (PGA-CP) at Weeks 2, 4, 8, 16 and 24

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    End point title
    		 Change From Baseline in Subjects Global Assessment of Cancer Pain (PGA-CP) at Weeks 2, 4, 8, 16 and 24
    End point description
    Subjects at specified time points were asked: “Considering all ways your cancer pain affects you,how are you doing today?” on a Likert scale range: 1 to 5, on IRT diaries. Scores: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,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: worsening of condition. mITT set analysed. Multiple imputation applied. 99999=summarised data not available. Individual values at wk 2,4,8,16,24 for 10mg: 0, 0, -3, 0, -2, 1, 0, -1,-1, 0, 1, 0, 0, -3, 1, 0, 0, -1, -1, 0, -1, 0, -3, 1, 0, -1, -1, -2, 0, -3, 1, 0,-1, -1, 0, -3, 1, 2,-1; for 10/20 mg: 1,0,1 respectively. 99999=no subjects analysed. N:subjects evaluable for endpoint. n:subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 8, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    71
    Units: Units on a scale
    least squares mean (standard error)
        Change at Week 2 (n=73, 1, 71,9)
    -0.39 ( 0.11 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.43 ( 0.12 )
        Change at Week 4 (n=73, 1, 71,9)
    -0.36 ( 0.14 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.66 ( 0.14 )
        Change at Week 8 (n=73, 1, 71,9)
    -0.23 ( 0.16 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.56 ( 0.17 )
        Change at Week 16 (n=73,0,71,6)
    -0.16 ( 0.16 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.32 ( 0.17 )
        Change at Week 24 (n=73,0,71,6)
    -0.19 ( 0.18 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.29 ( 0.17 )
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 2: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline global assessment score, baseline average pain intensity at the index bone metastasis cancer pain site, and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7045
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 0.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 4: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline global assessment score, baseline average pain intensity at the index bone metastasis cancer pain site, and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0402
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.59
         upper limit
    		 -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 8: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline global assessment score, baseline average pain intensity at the index bone metastasis cancer pain site, and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0637
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.67
         upper limit
    		 0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 16: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline global assessment score, baseline average pain intensity at the index bone metastasis cancer pain site, and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3804
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.53
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Change at Week 24: ANCOVA model for imputed datasets included treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and baseline global assessment score, baseline average pain intensity at the index bone metastasis cancer pain site, and baseline opioid dose as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5894
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.47
         upper limit
    		 0.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18

    Secondary: Number of Subjects With Reduction of >=2 Points From Baseline in PGA-CP Scores at Weeks 2, 4, 8, 16 and 24

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    End point title
    		 Number of Subjects With Reduction of >=2 Points From Baseline in PGA-CP Scores at Weeks 2, 4, 8, 16 and 24
    End point description
    Subjects at specified time points, answered to the following question, “Considering all the way your cancer pain affects you, how are you doing today?” on a Likert scale ranging from 1 to 5, on IRT diaries. Scores: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: worsening of condition. Efficacy data from subjects who were originally randomised to tanezumab 10 mg arm were not included in analyses of efficacy as pre-specified in protocol. So, summarised data is not reported for tanezumab 10 mg and 10/20 mg arms. Reported individual values. Here, ‘n’: subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 8, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Subjects
        Week 2 (n=73,9,1,72)
    7
    2
    0
    5
        Week 4 (n=73,9,1,72)
    9
    1
    0
    11
        Week 8 (n=73,9,1,72)
    10
    1
    0
    12
        Week 16 (n=73,6,1,72)
    9
    2
    0
    12
        Week 24 (n=73,6,1,72)
    9
    1
    0
    11
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2: Logistic regression model included baseline PGA-CP, baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2033
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.09
         upper limit
    		 1.69
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4: Logistic regression model included baseline PGA-CP, baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7627
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 3.41
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8: Logistic regression model included baseline PGA-CP, baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6894
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 3.43
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16: Logistic regression model included baseline PGA-CP, baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5905
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 3.83
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24: Logistic regression model included baseline PGA-CP, baseline average pain intensity at the index bone metastasis cancer pain site, treatment, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness).
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8354
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 3.35

    Secondary: Average Daily Total Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Average Daily Total Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    In this end point average daily opioid consumption was reported in milligram of morphine equivalent dose (mg of MED). mITT analysis set analysed. LOCF data applied. 99999:summarised data not available. Individual values at wk 1,2,4,6,8,12,16,24 for 10mg: 0.3, 30, 181.54, 1082.74, 122.03, 10, 120, 22.5,30, 0.3, 30, 182.4, 1082.22, 120.96, 10, 120, 22.5,30, 0.3, 34.28, 182.4, 1082.22, 120.96, 52.85, 120, 22.5,30, 0.3, 95, 182.4, 1081.54, 120.96, 10, 137.14, 22.5,30, 0.3, 122.14, 2.4, 1081.71, 120.96, 10, 120, 22.5,30, 0.3, 258.57, 2.4, 1.2, 88.45, 10, 120, 22.5,30, 0.3, 170, 2.4, 1.2, 86.31, 10, 120, 22.5,30, 0.3, 170, 2.4, 1.2, 88.45, 74.28, 120, 18.21,30; for 10/20mg: 510, 510,480, 510, 510, 480, 480, 480 respectively. N:subjects evaluable for endpoint. n:subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: mg of MED
    arithmetic mean (standard deviation)
        Week 1 (n=72,9,1,69)
    183.94 ( 275.05 )
    99999 ( 99999 )
    99999 ( 99999 )
    186.86 ( 351.83 )
        Week 2 (n=73,9,1,69)
    177.98 ( 270.67 )
    99999 ( 99999 )
    99999 ( 99999 )
    188.41 ( 356.15 )
        Week 4 (n=73,9,1,69)
    177.87 ( 266.93 )
    99999 ( 99999 )
    99999 ( 99999 )
    181.32 ( 349.82 )
        Week 6 (n=73,9,1,70)
    186.20 ( 280.44 )
    99999 ( 99999 )
    99999 ( 99999 )
    173.45 ( 346.27 )
        Week 8 (n=73,9,1,70)
    188.10 ( 281.01 )
    99999 ( 99999 )
    99999 ( 99999 )
    170.31 ( 327.19 )
        Week 12 (n=73,9,1,70)
    187.43 ( 336.74 )
    99999 ( 99999 )
    99999 ( 99999 )
    177.06 ( 332.39 )
        Week 16 (n=73,9,1,70)
    189.62 ( 333.77 )
    99999 ( 99999 )
    99999 ( 99999 )
    173.48 ( 329.17 )
        Week 24 (n=73,9,1,70)
    189.78 ( 353.10 )
    99999 ( 99999 )
    99999 ( 99999 )
    346.95 ( 1537.00 )
    No statistical analyses for this end point

    Secondary: Average Number of Doses of Rescue Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24

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    End point title
    		 Average Number of Doses of Rescue Opioid Consumption at Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point description
    In this end point average number of doses of rescue opioid consumption at specified time points were reported. mITT analysis set analysed. LOCF data applied. 99999: summarised data not available. Individual values at wk 1,2,4,6,8,12,16,24 for 10mg: 1, 1, 1, 1, 0.14, 1,1, 1, 1, 1, 1, 1, 0.14, 1,1,1, 1, 1, 1, 1, 0.14, 0.14, 0.85,1,1, 1, 1, 1, 0.85, 0.14, 0.14, 1, 1,1, 1, 1, 1, 1, 0.28, 0.14, 0.71, 1,1, 1, 1, 1, 1, 1, 0.14, 0.14, 1,1, 1, 1, 1, 1, 0.85, 0.14, 0.14, 1,1, 1, 1, 1, 1, 1, 0.14, 0.14, 0.42,1; for 10/20mg: 1,1, 0.43, 1, 1, 1, 1, 1 respectively. N:subjects evaluable for endpoint. n:subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 6, 8, 12, 16 and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Doses
    arithmetic mean (standard deviation)
        Week 1 (n=52,8,1,42)
    1.15 ( 0.76 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.96 ( 0.48 )
        Week 2 (n=54,8,1,44)
    1.11 ( 0.69 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.89 ( 0.52 )
        Week 4 (n=56,9,1,46)
    1.08 ( 0.69 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.80 ( 0.57 )
        Week 6 (n=61,9,1,48)
    0.95 ( 0.70 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.80 ( 0.65 )
        Week 8 (n=61,9,1,48)
    0.99 ( 0.72 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.81 ( 0.61 )
        Week 12 (n=61,9,1,48)
    0.92 ( 0.94 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.73 ( 0.57 )
        Week 16 (n=62,9,1,48)
    0.86 ( 0.93 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.75 ( 0.57 )
        Week 24 (n=65,9,1,49)
    0.79 ( 0.93 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.69 ( 0.57 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in the Weekly Opioid-Related Symptom Distress Scale (OR-SDS) at Weeks 2, 4, 8, 16, and 24

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    End point title
    		 Change From Baseline in the Weekly Opioid-Related Symptom Distress Scale (OR-SDS) at Weeks 2, 4, 8, 16, and 24
    End point description
    OR 12 symptoms(Ss) evaluated. Range:severity(none=0 to very severe=4),distress(none =0 to very much=5);frequency(none =0 to almost constantly =4;subjects reported number of retching/vomiting episodes(none =0, 1-2 episodes =1, 3-4 episodes =2, 5-6 episodes =3, >6 episodes =4).Frequency(F)composite score:mean of F scores from all Ss, 0(none) to 4(almost constantly);Severity(S) composite score:mean of S scores from all 12 Ss, 0(none) to 4(max severity);Distress(D)composite score:mean of D scores from all 12 symptoms,0(none) to 5(max distress).Multi domain avg(MDA):avg of each Ss for F,S,D; 0(none)to 4.34(worse);higher scores=worse condition in all domains.99999=Individual values at wk 2,4,8,16,24 for 10 mg:-1,0,-1,-0.67,-0.6,0.2,-0.25,-0.22,-0.8,0,-0.25,-0.35,-1,0,-0.75,-0.58;10/20 mg: -1.33,-0.83,0.17,-0.67,-1.5,-0.5,0,-0.67,-1,-0.75,0.25,-0.5 respectively.9999=not analysed. N:subjects evaluable for endpoint. n:subjects at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 8, 16, and 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    2
    1
    72
    Units: Units on a scale
    least squares mean (standard error)
        Change at Week2: F Composite Score (n=73,1,72,1)
    -0.06 ( 0.16 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.11 ( 0.17 )
        Change at Week 2: S Composite Score (n=73,1,72,1)
    -0.18 ( 0.11 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.02 ( 0.12 )
        Change at Week 2: D Composite Score (n=73,1,72,1)
    -0.08 ( 0.18 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.09 ( 0.19 )
        Change at Week2:MDA Composite Score (n=73,1,72,1)
    -0.10 ( 0.14 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.02 ( 0.15 )
        Change at Week 4: F Composite Score (n=73,1,72,1)
    -0.19 ( 0.14 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.12 ( 0.14 )
        Change at Week 4: S Composite Score (n=73,1,72,1)
    -0.10 ( 0.12 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.01 ( 0.13 )
        Change at Week 4: D Composite Score (n=73,1,72,1)
    0.12 ( 0.15 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.11 ( 0.15 )
        Change at Week4:MDA Composite Score (n=73,1,72,1)
    -0.06 ( 0.12 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.00 ( 0.13 )
        Change at Week 8: F Composite Score (n=73,1,72,2)
    0.07 ( 0.15 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.10 ( 0.16 )
        Change at Week 8: S Composite Score (n=73,1,72,2)
    -0.07 ( 0.12 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.17 ( 0.13 )
        Change at Week 8: D Composite Score (n=73,1,72,2)
    0.03 ( 0.19 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.26 ( 0.20 )
        Change at Week8:MDA Composite Score (n=73,1,72,2)
    0.02 ( 0.13 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.02 ( 0.14 )
        Change at Week 16: F Composite Score (n=73,0,72,1)
    0.08 ( 0.19 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.07 ( 0.22 )
        Change at Week 16: S Composite Score (n=73,0,72,1)
    -0.12 ( 0.15 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.08 ( 0.17 )
        Change at Week 16: D Composite Score (n=73,0,72,1)
    0.10 ( 0.20 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.07 ( 0.24 )
        Change at Week16:MDA Composite Score(n=73,0,72,1)
    0.02 ( 0.16 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.04 ( 0.19 )
        Change at Week 24: F Composite Score (n=73,0,72,0)
    0.29 ( 0.21 )
    99999 ( 99999 )
    99999 ( 99999 )
    -0.13 ( 0.24 )
        Change at Week 24: S Composite Score (n=73,0,72,0)
    -0.01 ( 0.17 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.16 ( 0.18 )
        Change at Week24: D Composite Score (n=73,0,72,0)
    0.33 ( 0.21 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.22 ( 0.23 )
        Change at Week24:MDA Composite Score (n=73,0,72,0)
    0.17 ( 0.18 )
    99999 ( 99999 )
    99999 ( 99999 )
    0.07 ( 0.20 )
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Frequency Composite Score: Mixed model for repeated measurements (MMRM) model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS frequency scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8069
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.49
         upper limit
    		 0.38
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.22
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Frequency Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS frequency scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3933
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.57
         upper limit
    		 0.23
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Frequency Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS frequency scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7127
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 0.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Frequency Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS frequency scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1814
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.05
         upper limit
    		 0.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Frequency Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS frequency scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5869
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.71
         upper limit
    		 0.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.28
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Severity Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS severity scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2822
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Severity Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS severity scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5795
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.23
         upper limit
    		 0.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.16
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Severity Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS severity scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3692
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.24
         upper limit
    		 0.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.22
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Severity Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS severity scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5486
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.42
         upper limit
    		 0.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.16
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Severity Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS severity scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4724
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.23
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 Distress Composite Score: MMRM model includes time (study week), treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS distress scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.477
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.23
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 Distress Composite Score: MMRM model includes time (study week), treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS distress scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5607
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.77
         upper limit
    		 0.42
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.29
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 Distress Composite Score: MMRM model includes time (study week), treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS distress scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9791
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.38
         upper limit
    		 0.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 Distress Composite Score: MMRM model includes time (study week), treatment, region, and randomization stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS distress scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3574
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.27
         upper limit
    		 0.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 Distress Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS distress scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7143
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.68
         upper limit
    		 0.47
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.28
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 2 MDA Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS MDA scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6381
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.28
         upper limit
    		 0.45
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.18
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 4 MDA Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS MDA scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7181
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.25
         upper limit
    		 0.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 8 MDA Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS MDA scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8378
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in least square (LS) mean
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.38
         upper limit
    		 0.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 24 MDA Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS MDA scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6719
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.62
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Statistical analysis title
    		 Placebo vs Tanezumab 20mg
    Statistical analysis description
    Week 16 MDA Composite Score: MMRM model includes time (study week), treatment, region, and randomisation stratification variables (concomitant anticancer treatment and tumor aggressiveness) as fixed effects, and treatment*time interaction, baseline OR-SDS MDA scores, and baseline average pain intensity at the index bone metastasis cancer pain site as covariates.
    Comparison groups
    Placebo v Tanezumab 20 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.795
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in LS mean
    Point estimate
    -0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.52
         upper limit
    		 0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.23

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalisation; 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 24 weeks post last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs. Subjects were followed up to 24 weeks after study drug last dose. The safety analysis set was defined as all subjects treated with tanezumab or placebo SC, including subjects who received tanezumab 10 mg prior to protocol amendment 3.
    End point type
    Secondary
    End point timeframe
    Day 1 of dosing up to 24 weeks post last dose (maximum up to Week 48)
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Subjects
    52
    9
    1
    62
    No statistical analyses for this end point

    Secondary: Number of Subjects With Laboratory Abnormalities (Normal Baseline)

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    End point title
    		 Number of Subjects With Laboratory Abnormalities (Normal Baseline)
    End point description
    Lab abnormality criteria:hemoglobin(HGB);hematocrit;erythrocytes< 0.8*lower limit of normal(LLN);erythrocyte mean corpuscular volume/HGB/ HGB conce.,erythrocytes distribution width<0.9*LLN, >1.1*upper(U)LN; platelets<0.5*LLN,>1.75* ULN;leukocytes<0.6*LLN,>1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN; basophils, eosinophils, monocytes >1.2*ULN; total bilirubin>1.5*ULN; activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio>1.1*ULN; bilirubin >1.5*ULN; aspartate aminotransferase(AT), alanine AT,gamma glutamyl transferase,lactate dehydrogenase,alkaline phosphatase >3.0*ULN; protein;albumin<0.8*LLN, >1.2*ULN; 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; Urine:glucose, ketones, protein, HGB, bilirubin, nitrite >=1.Safety analysis set analysed. N:subjects evaluable for endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, before dosing) up to Week 48
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    42
    8
    0 [10]
    50
    Units: Subjects
    18
    1
    20
    Notes
    [10] - No subjects met criteria for data collection and analysis for 10/20 mg for this end point.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Laboratory Abnormalities (Abnormal Baseline)

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    End point title
    		 Number of Subjects With Laboratory Abnormalities (Abnormal Baseline)
    End point description
    Laboratory abnormality criteria included: HGB; hematocrit; erythrocytes < 0.8* LLN; erythrocyte mean corpuscular volume/HGB/ HGB concentration, erythrocytes distribution width <0.9*LLN, >1.1*upper limit of normal (ULN); platelets <0.5*LLN,>1.75* ULN; leukocytes <0.6*LLN, >1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN; basophils, eosinophils, monocytes >1.2*ULN; activated partial thromboplastin time, prothrombin time >1.1*ULN; bilirubin>1.5*ULN; aspartate AT, alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase >3.0*ULN; protein; albumin<0.8*LLN, >1.2*ULN; urea nitrogen, 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; creatine kinase >2.0*ULN. Safety analysis set analysed. N:subjects evaluable for endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, before dosing) up to Week 48
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    38
    8
    0 [11]
    46
    Units: Subjects
    15
    2
    14
    Notes
    [11] - No subjects met criteria for data collection and analysis for 10/20 mg for this end point.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Categorical Change From Baseline to Last Post-Baseline in Sitting Systolic and Diastolic Blood Pressure During Treatment Period

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    End point title
    		 Number of Subjects With Categorical Change From Baseline to Last Post-Baseline in Sitting Systolic and Diastolic Blood Pressure During Treatment Period
    End point description
    Change categories for sitting systolic blood pressure (SBP) measured in millimeter of mercury (mm Hg) were as follows: change <=-40, change >-40 to -30, change >-30 to -20, change >-20 to -10, change >-10 to 0, change >0 to <10, change >=10 to <20, change >=20 to <30, change >=30 to <40 and change >=40. Change categories for sitting diastolic blood pressure (DBP) measured in mm Hg were as follow: change <=-30, change >-30 to -20, change >-20 to -10, change >-10 to 0, change >0 to <10, change >=10 to <20, change >=20 to <30 and change >=30. Rows with only non-zero data/values, for at least 1 reporting arm, are reported below. Safety analysis set: all subjects treated with tanezumab or placebo SC, including subjects received tanezumab 10 mg prior to protocol amendment 3. N:subjects evaluable for endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, before dosing) up to Week 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    67
    9
    1
    68
    Units: Subjects
        Sitting SBP(mmHg)Change <=-40
    1
    0
    0
    1
        Sitting SBP(mmHg)Change >-40 to -30
    1
    0
    0
    2
        Sitting SBP(mmHg) Change >-30 to -20
    6
    0
    1
    3
        Sitting SBP(mmHg) Change >-20 to -10
    10
    3
    0
    14
        Sitting SBP(mmHg) Change >-10 to 0
    26
    2
    0
    25
        Sitting SBP(mmHg) Change >0 to <10
    12
    1
    0
    9
        Sitting SBP(mmHg) Change >=10 to <20
    6
    3
    0
    10
        Sitting SBP(mmHg) Change >=20 to <30
    5
    0
    0
    3
        Sitting SBP(mmHg) Change >=30 to <40
    0
    0
    0
    1
        Sitting DBP (mmHg) Change >-30 to -20
    0
    1
    0
    1
        Sitting DBP(mmHg) Change >-20 to -10
    10
    1
    1
    13
        Sitting DBP(mmHg) Change >-10 to 0
    39
    4
    0
    26
        Sitting DBP(mmHg) Change >0 to <10
    11
    0
    0
    18
        Sitting DBP(mmHg) Change >=10 to <20
    5
    2
    0
    9
        Sitting DBP(mmHg) Change >=20 to <30
    2
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Categorical Summary of Electrocardiogram (ECG) (QTC) Data

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    End point title
    		 Number of Subjects With Categorical Summary of Electrocardiogram (ECG) (QTC) Data
    End point description
    Electrocardiogram assessment included QT interval corrected using Fridericia's formula (QTcF), QT interval corrected using Bazett's formula (QTcB), both had following categories: 450<=Value<480 millisecond (msec), 480<=Value<500 msec and Value>=500 msec. Safety analysis set: all subjects treated with tanezumab or placebo SC, including subjects received tanezumab 10 mg prior to protocol amendment 3. In reporting arm “Tanezumab10/20 mg”, the subject did not have post-baseline results evaluated against ECG (QTC) criteria, hence was not evaluable for this end point. N:subjects evaluable for endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, before dosing) up to Week 24
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    40
    8
    0 [12]
    44
    Units: Subjects
        QTCB Interval 450<=Value<480
    2
    1
    6
        QTCB Interval 480<=Value<500
    0
    0
    1
        QTCF Interval 450<=Value<480
    1
    0
    5
    Notes
    [12] - No subjects met criteria for data collection and analysis for 10/20 mg for this end point.
    No statistical analyses for this end point

    Secondary: Number of Subjects with Confirmed Orthostatic Hypotension

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    End point title
    		 Number of Subjects with Confirmed Orthostatic Hypotension
    End point description
    Orthostatic hypotension was defined as postural change (supine to standing) that met the following criteria: for systolic blood pressure (BP) less than or equal to (<=) 150 millimeter of mercury (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 greater than (>) 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. Safety analysis set: all subjects treated with tanezumab or placebo SC, including subjects received tanezumab 10 mg prior to protocol amendment 3. N:subjects evaluable for endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, before dosing), Weeks 8, 16, 24 and 48
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Subjects
        Baseline
    0
    0
    0
    0
        Week 8
    0
    0
    0
    0
        Week 16
    0
    0
    0
    1
        Week 24
    0
    0
    0
    0
        Week 48
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Findings in Weight Measurement, Counted as an AE

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    End point title
    		 Number of Subjects With Clinically Significant Findings in Weight Measurement, Counted as an AE
    End point description
    The number of subjects with clinically significant findings in weight measurement and were counted as an AE in the study were reported in this outcome measure. Safety analysis set: all subjects treated with tanezumab or placebo SC, including subjects received tanezumab 10 mg prior to protocol amendment 3.
    End point type
    Secondary
    End point timeframe
    Day 1 of dosing up to maximum of Week 48
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Subjects
    2
    0
    0
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Abnormal Physical Examination at Screening

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    End point title
    		 Number of Subjects With Abnormal Physical Examination at Screening
    End point description
    Physical examination included assessment of general, head, eyes, ears, nose, neck, thyroid, lungs, heart, abdomen, extremities, skin, throat and other. Investigator judged abnormality in physical examinations. Safety analysis set: all subjects treated with tanezumab or placebo SC, including subjects received tanezumab 10 mg prior to protocol amendment 3. N:subjects evaluable for endpoint. n:subjects evaluable at specified assessments.
    End point type
    Secondary
    End point timeframe
    Screening (up to 37 days prior to Day 1)
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    72
    9
    1
    72
    Units: Subjects
        General
    3
    1
    0
    6
        Head
    2
    1
    0
    1
        Eyes
    4
    1
    0
    1
        Ears
    1
    0
    0
    1
        Nose
    0
    0
    0
    0
        Neck
    2
    1
    0
    2
        Thyroid
    2
    0
    0
    0
        Lungs
    5
    1
    0
    3
        Heart
    2
    2
    0
    3
        Abdomen
    2
    1
    1
    5
        Extremities
    14
    0
    0
    10
        Skin
    15
    2
    0
    10
        Throat
    3
    1
    0
    2
        Other 1
    9
    3
    0
    6
        Other 2
    1
    3
    0
    2
        Other 3
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Individual Adjudicated Joint Safety Outcome/Event

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    End point title
    		 Number of Subjects With Individual Adjudicated Joint Safety Outcome/Event
    End point description
    Joint-related safety events resulting in total joint replacement and/or discontinuation from the study as well as adverse events were reviewed by the External Adjudication Committee to confirm the potential events as adjudicated join safety event. In this endpoint, number of subjects with any of the joint safety adjudication outcomes of primary osteonecrosis, rapidly progressive osteoarthritis (OA) (type 1 and type 2), subchondral insufficiency fracture (or SPONK), or pathological fracture were reported. Other adjudication outcomes included normal progression of OA and other joint outcome. Safety analysis set was analysed. N:subjects evaluable for endpoint. n:subjects evaluable at specified assessments. In reporting arm, “Tanezumab10/20 mg” the subject did not have potential joint related safety event for analysis by Adjudication Committee.
    End point type
    Secondary
    End point timeframe
    During the study, maximum up to Week 48
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    1
    1
    0 [13]
    3
    Units: Subjects
        Rapidly Progressive OA
    0
    0
    0
        Rapidly Progressive OA type 1
    0
    0
    0
        Rapidly Progressive OA type 2
    0
    0
    0
        Primary Osteonecrosis
    0
    0
    0
        Pathological Fracture
    0
    0
    2
        Subchondral Insufficiency Fracture
    0
    0
    0
        Normal Progression of OA
    0
    0
    0
        Other Joint Outcome
    1
    1
    1
    Notes
    [13] - No subjects met criteria for data collection and analysis for 10/20 mg for this end point.
    No statistical analyses for this end point

    Secondary: Number of Subjects With At Least 1 Total Joint Replacements (TJR)

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    End point title
    		 Number of Subjects With At Least 1 Total Joint Replacements (TJR)
    End point description
    Number of subjects with joint replacement surgery were reported. The safety analysis set included all subjects treated with tanezumab or placebo SC, including subjects who received tanezumab 10 mg prior to protocol amendment 3.
    End point type
    Secondary
    End point timeframe
    During the study, maximum up to Week 48
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Subjects
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Anti-Drug Antibodies (ADA) and Neutralising Anti-Drug Antibodies (NAb)

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    End point title
    		 Number of Subjects With Anti-Drug Antibodies (ADA) and Neutralising Anti-Drug Antibodies (NAb)
    End point description
    Human serum ADA samples were analysed for the presence or absence of anti-tanezumab antibodies by using a semi quantitative enzyme linked immunosorbent assay (ELISA). Number of subjects with presence of anti-tanezumab antibodies and neutralising anti-drug antibodies are reported. The safety analysis set included all subjects treated with tanezumab or placebo SC, including subjects who received tanezumab 10 mg prior to protocol amendment 3.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, before dosing) up to Week 48
    End point values
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Number of subjects analysed
    73
    9
    1
    72
    Units: Subjects
        ADA
    0
    0
    0
    1
        NAb
    0
    0
    0
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 of dosing up to 24 weeks post last dose (maximum up to Week 48)
    Adverse event reporting additional description
    Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorised as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. Safety analysis set was evaluated.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received placebo matched to tanezumab SC once every 8 weeks for 24 weeks.

    Reporting group title
    Tanezumab 10 mg
    Reporting group description
    		 Subjects in this discontinued treatment arm, received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and completed their treatment before the amendment.

    Reporting group title
    Tanezumab 10/20 mg
    Reporting group description
    		 Subjects in this treatment group had received tanezumab 10 mg SC once every 8 weeks before protocol amendment 3 and after the amendment they continued remaining treatment with tanezumab 20 mg SC once every 8 weeks.

    Reporting group title
    Tanezumab 20 mg
    Reporting group description
    		 Subjects received tanezumab 20 mg SC once every 8 weeks for 24 weeks.

    Serious adverse events
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    28 / 73 (38.36%)
    2 / 9 (22.22%)
    1 / 1 (100.00%)
    39 / 72 (54.17%)
         number of deaths (all causes)
    3
    0
    0
    3
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder neoplasm
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Breast cancer
         subjects affected / exposed
    5 / 73 (6.85%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Cancer pain
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Colon cancer
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         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
    Colorectal cancer
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Gastric cancer
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Laryngeal cancer
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Lung neoplasm malignant
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    4 / 72 (5.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Metastases to bone
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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 / 1
    Metastases to meninges
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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 prostate
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    7 / 73 (9.59%)
    1 / 9 (11.11%)
    1 / 1 (100.00%)
    7 / 72 (9.72%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Peripheral ischaemia
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Gait disturbance
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Pyrexia
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (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, thoracic and mediastinal disorders
    Bronchitis chronic
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Pleurisy
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Pulmonary embolism
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         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
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Radius fracture
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Spinal compression fracture
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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 disorders
    Arrhythmia
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Nervous system disorders
    Cerebrovascular insufficiency
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Dizziness
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Paraparesis
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    1 / 1 (100.00%)
    3 / 72 (4.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Diarrhoea
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (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
    Flatulence
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Vomiting
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Hepatobiliary disorders
    Jaundice
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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 retention
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (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
    Osteonecrosis of jaw
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Pathological fracture
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (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
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Metabolism and nutrition disorders
    Hypophagia
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         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
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Placebo Tanezumab 10 mg Tanezumab 10/20 mg Tanezumab 20 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    43 / 73 (58.90%)
    8 / 9 (88.89%)
    1 / 1 (100.00%)
    49 / 72 (68.06%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    1
    0
    0
    3
    Breast cancer
         subjects affected / exposed
    2 / 73 (2.74%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    4 / 72 (5.56%)
         occurrences all number
    2
    1
    0
    5
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences all number
    0
    1
    0
    1
    Metastases to bone
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences all number
    0
    1
    0
    2
    Neoplasm
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Prostate cancer
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences all number
    2
    0
    0
    3
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    1
    0
    0
    2
    Lymphoedema
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 73 (1.37%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences all number
    1
    1
    0
    1
    Pallor
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    0
    0
    0
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 73 (5.48%)
    0 / 9 (0.00%)
    1 / 1 (100.00%)
    6 / 72 (8.33%)
         occurrences all number
    4
    0
    1
    9
    Fatigue
         subjects affected / exposed
    5 / 73 (6.85%)
    1 / 9 (11.11%)
    1 / 1 (100.00%)
    6 / 72 (8.33%)
         occurrences all number
    7
    5
    1
    6
    Influenza like illness
         subjects affected / exposed
    1 / 73 (1.37%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    4 / 72 (5.56%)
         occurrences all number
    1
    1
    0
    5
    Pain
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    6 / 72 (8.33%)
         occurrences all number
    4
    0
    0
    8
    Oedema peripheral
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    9 / 72 (12.50%)
         occurrences all number
    2
    0
    0
    9
    Peripheral swelling
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    1
    0
    0
    2
    Pyrexia
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    2
    0
    0
    2
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 73 (2.74%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    2
    1
    0
    2
    Dyspnoea
         subjects affected / exposed
    3 / 73 (4.11%)
    2 / 9 (22.22%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences all number
    3
    2
    0
    5
    Oropharyngeal pain
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Pulmonary mass
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Wheezing
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Depression
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    2
    0
    0
    2
    Depressed mood
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    1 / 1 (100.00%)
    2 / 72 (2.78%)
         occurrences all number
    5
    0
    1
    5
    Insomnia
         subjects affected / exposed
    1 / 73 (1.37%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    5 / 72 (6.94%)
         occurrences all number
    1
    1
    0
    5
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences all number
    3
    0
    0
    3
    White blood cell count decreased
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    6
    0
    0
    0
    Weight increased
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    5 / 72 (6.94%)
         occurrences all number
    4
    0
    0
    7
    Toxicity to various agents
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences all number
    3
    0
    0
    4
    Headache
         subjects affected / exposed
    2 / 73 (2.74%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    5 / 72 (6.94%)
         occurrences all number
    2
    1
    0
    5
    Neuralgia
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    4
    0
    0
    3
    Paraesthesia
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    0
    0
    0
    6
    Somnolence
         subjects affected / exposed
    2 / 73 (2.74%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    2
    1
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    9 / 73 (12.33%)
    1 / 9 (11.11%)
    1 / 1 (100.00%)
    9 / 72 (12.50%)
         occurrences all number
    9
    1
    2
    10
    Leukopenia
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    3
    0
    0
    2
    Thrombocytopenia
         subjects affected / exposed
    1 / 73 (1.37%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Eye disorders
    Visual acuity reduced
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Constipation
         subjects affected / exposed
    3 / 73 (4.11%)
    2 / 9 (22.22%)
    1 / 1 (100.00%)
    6 / 72 (8.33%)
         occurrences all number
    3
    2
    1
    6
    Diarrhoea
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    6 / 72 (8.33%)
         occurrences all number
    1
    0
    0
    7
    Dyspepsia
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences all number
    2
    0
    0
    3
    Gastritis
         subjects affected / exposed
    1 / 73 (1.37%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Nausea
         subjects affected / exposed
    6 / 73 (8.22%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    4 / 72 (5.56%)
         occurrences all number
    8
    0
    0
    7
    Toothache
         subjects affected / exposed
    4 / 73 (5.48%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    5
    0
    0
    0
    Vomiting
         subjects affected / exposed
    6 / 73 (8.22%)
    0 / 9 (0.00%)
    1 / 1 (100.00%)
    4 / 72 (5.56%)
         occurrences all number
    7
    0
    1
    5
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    3 / 73 (4.11%)
    2 / 9 (22.22%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    3
    2
    0
    3
    Decubitus ulcer
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    2
    0
    0
    2
    Rash
         subjects affected / exposed
    4 / 73 (5.48%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences all number
    4
    0
    0
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Urinary incontinence
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    9 / 73 (12.33%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences all number
    14
    1
    0
    2
    Arthralgia
         subjects affected / exposed
    7 / 73 (9.59%)
    2 / 9 (22.22%)
    0 / 1 (0.00%)
    11 / 72 (15.28%)
         occurrences all number
    18
    2
    0
    16
    Myalgia
         subjects affected / exposed
    1 / 73 (1.37%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    1
    0
    0
    2
    Pain in extremity
         subjects affected / exposed
    5 / 73 (6.85%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences all number
    6
    0
    0
    4
    Pathological fracture
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences all number
    0
    0
    0
    3
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    0
    0
    0
    2
    Bronchitis
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    2 / 72 (2.78%)
         occurrences all number
    1
    0
    0
    2
    Cystitis
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    4 / 72 (5.56%)
         occurrences all number
    2
    0
    0
    4
    Oral candidiasis
         subjects affected / exposed
    0 / 73 (0.00%)
    1 / 9 (11.11%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences all number
    0
    1
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    3 / 72 (4.17%)
         occurrences all number
    0
    0
    0
    3
    Urinary tract infection
         subjects affected / exposed
    1 / 73 (1.37%)
    0 / 9 (0.00%)
    1 / 1 (100.00%)
    1 / 72 (1.39%)
         occurrences all number
    1
    0
    1
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    4 / 73 (5.48%)
    1 / 9 (11.11%)
    1 / 1 (100.00%)
    10 / 72 (13.89%)
         occurrences all number
    5
    1
    2
    10
    Dehydration
         subjects affected / exposed
    0 / 73 (0.00%)
    0 / 9 (0.00%)
    1 / 1 (100.00%)
    2 / 72 (2.78%)
         occurrences all number
    0
    0
    1
    2
    Hypocalcaemia
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    3 / 73 (4.11%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    1 / 72 (1.39%)
         occurrences all number
    3
    0
    0
    1
    Hypomagnesaemia
         subjects affected / exposed
    2 / 73 (2.74%)
    0 / 9 (0.00%)
    0 / 1 (0.00%)
    0 / 72 (0.00%)
         occurrences all number
    2
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Feb 2017
    To provide background and rationale for key changes

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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