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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 in Subjects with Osteoarthritis of the Hip Or Knee

Summary
EudraCT number	2013-004508-21
Trial protocol	DE AT GB PT HU FI SK ES SE BG IT
Global end of trial date	14 Nov 2018

Results information
Results version number	v1(current)
This version publication date	08 Nov 2019
First version publication date	08 Nov 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

A4091057

ISRCTN number

US NCT number

NCT02709486

WHO universal trial number (UTN)

Other trial identifiers

Other Identifier: Alias Study Number: OA 6-MONTH EU STUDY

Sponsor organisation name

Pfizer, Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

02 Mar 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Nov 2018

Was the trial ended prematurely?

Main objective of the trial

To demonstrate superior efficacy of tanezumab 5 milligrams (mg) and 2.5 mg administered subcutaneously (SC) every 8 weeks versus placebo at Week 24.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

02 Mar 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 27

Country: Number of subjects enrolled

Bulgaria: 70

Country: Number of subjects enrolled

Finland: 11

Country: Number of subjects enrolled

France: 18

Country: Number of subjects enrolled

Germany: 46

Country: Number of subjects enrolled

Hungary: 87

Country: Number of subjects enrolled

Italy: 15

Country: Number of subjects enrolled

Japan: 106

Country: Number of subjects enrolled

Poland: 75

Country: Number of subjects enrolled

Portugal: 1

Country: Number of subjects enrolled

Romania: 61

Country: Number of subjects enrolled

Slovakia: 37

Country: Number of subjects enrolled

Spain: 206

Country: Number of subjects enrolled

Sweden: 67

Country: Number of subjects enrolled

United Kingdom: 22

Worldwide total number of subjects

849

EEA total number of subjects

743

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

391

From 65 to 84 years

449

85 years and over

Subject disposition

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Recruitment details

Screening details

The study was conducted at 141 sites in 15 countries. Twenty (20) sites were terminated.

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

Are arms mutually exclusive

Yes

Placebo

Arm description

Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Arm type

Placebo

Investigational medicinal product name

Placebo

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 injection administered subcutaneously (matched to tanezumab [RN624 or PF-04383119]) on Day 1 (Baseline), Week 8 and Week 16.

Tanezumab 2.5 mg

Arm description

Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Arm type

Experimental

Investigational medicinal product name

Tanezumab

Investigational medicinal product code

RN624 or PF- 04383119

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Tanezumab (RN624 or PF-04383119) 2.5 mg injection, subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Tanezumab 5 mg

Arm description

Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Arm type

Experimental

Investigational medicinal product name

Tanezumab

Investigational medicinal product code

RN624 or PF- 04383119

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Tanezumab (RN624 or PF-04383119) 5 mg injection, subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Number of subjects in period 1	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Started	282	283	284
Completed	238	249	239
Not completed	44	34	45
Adverse event, serious fatal	-	-	2
Consent withdrawn by subject	32	22	32
Adverse event	2	5	3
Unspecified	-	2	3
Lost to follow-up	3	2	2
Insufficient clinical response	7	3	3

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Reporting group title

Tanezumab 2.5 mg

Reporting group description

Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Reporting group title

Tanezumab 5 mg

Reporting group description

Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Reporting group values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg	Total
Number of subjects	282	283	284	849
Age categorical
The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously.
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	138	138	115	391
From 65-84 years	142	143	164	449
85 years and over	2	2	5	9
Age Continuous
The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously.
Units: years
arithmetic mean (standard deviation)	64.24 ± 9.58	65.17 ± 8.39	65.23 ± 10.16	-
Sex: Female, Male
The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously.
Units: Subjects
Female	196	198	193	587
Male	86	85	91	262
Race/Ethnicity, Customized
The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously.
Units: Subjects
White	247	245	248	740
Black or African American	0	0	0	0
Asian	34	38	34	106
Other	1	0	2	3
Unknown	0	0	0	0
Ethnicity (NIH/OMB)
The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously.
Units: Subjects
Hispanic or Latino	19	19	10	48
Not Hispanic or Latino	263	264	274	801
Unknown or Not Reported	0	0	0	0

End points

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Reporting group title

Placebo

Reporting group description

Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Reporting group title

Tanezumab 2.5 mg

Reporting group description

Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Reporting group title

Tanezumab 5 mg

Reporting group description

Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Primary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24

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End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24

End point description

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with osteoarthritis (OA). The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours (hrs). It was calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. The intent to treat (ITT) population included all randomized subjects who received at least one dose of subcutaneous (SC) study medication (either tanezumab or placebo).

End point type

Primary

End point timeframe

Baseline, Week 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)	-2.24 ± 0.17	-2.70 ± 0.17	-2.85 ± 0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. Analysis of covariance (ANCOVA) model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.0088 ^[2]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.18

Notes
[1] - Step-down testing procedure within each of the primary end points was applied to maintain Type I error. Tanezumab 5 mg versus placebo was tested first and if found significant, then the testing was continued for Tanezumab 2.5 mg versus placebo. Tanezumab treatment group was declared as superior to placebo if the corresponding treatment contrast was significant over all 3 primary end points.
[2] - Threshold for significance at 0.05 level.

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.0006 ^[4]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-0.97

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.18

Notes
[3] - A step-down testing procedure within each of the primary end points was applied to maintain Type I error. Tanezumab 5 mg versus placebo was tested first and if found significant, then the testing was continued for Tanezumab 2.5 mg versus placebo. A tanezumab treatment group was declared as superior to placebo if the corresponding treatment contrast was significant over all 3 primary end points.
[4] - Threshold for significance at 0.05 level.

Primary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24

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End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24

End point description

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. Physical function refers to subjects ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Primary

End point timeframe

Baseline, Week 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)	-2.11 ± 0.17	-2.70 ± 0.17	-2.82 ± 0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.0008 ^[6]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

-0.24

Variability estimate

Standard error of the mean

Dispersion value

0.18

Notes
[5] - Step-down testing procedure within each of the primary end points was applied to maintain Type I error. Tanezumab 5 mg versus placebo was tested first and if found significant, then the testing was continued for Tanezumab 2.5 mg versus placebo. Tanezumab treatment group was declared as superior to placebo if the corresponding treatment contrast was significant over all 3 primary end points.
[6] - Threshold for significance at 0.05 level.

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

< 0.0001 ^[8]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.36

Variability estimate

Standard error of the mean

Dispersion value

0.17

Notes
[7] - Step-down testing procedure within each of the primary end points was applied to maintain Type I error. Tanezumab 5 mg versus placebo was tested first and if found significant, then the testing was continued for Tanezumab 2.5 mg versus placebo. Tanezumab treatment group was declared as superior to placebo if the corresponding treatment contrast was significant over all 3 primary end points.
[8] - Threshold for significance at 0.05 level.

Primary: Change from Baseline in the Patient’s Global Assessment (PGA) of Osteoarthritis at Week 24

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End point title

Change from Baseline in the Patient’s Global Assessment (PGA) of Osteoarthritis at Week 24

End point description

PGA of OA was assessed by asking a question from subjects: “Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Subjects responded on a scale ranging from 1-5, where 1=very good (no symptom 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 and inability to carry out all normal activities). Higher scores indicated worsening of condition. The intent to treat population was defined as all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Primary

End point timeframe

Baseline, Week 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)	-0.72 ± 0.06	-0.82 ± 0.06	-0.90 ± 0.06

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.1092 ^[10]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.02

Variability estimate

Standard error of the mean

Dispersion value

0.07

Notes
[9] - A step-down testing procedure within each of the primary end points was applied to maintain Type I error. Tanezumab 5 mg versus placebo was tested first and if found significant, then the testing was continued for Tanezumab 2.5 mg versus placebo. A tanezumab treatment group was declared as superior to placebo if the corresponding treatment contrast was significant over all 3 primary end points.
[10] - Threshold for significance at 0.05 level.

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

= 0.0051 ^[12]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.07

Notes
[11] - A step-down testing procedure within each of the primary end points was applied to maintain Type I error. Tanezumab 5 mg versus placebo was tested first and if found significant, then the testing was continued for Tanezumab 2.5 mg versus placebo. A tanezumab treatment group was declared as superior to placebo if the corresponding treatment contrast was significant over all 3 primary end points.
[12] - Threshold for significance at 0.05 level.

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16

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End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16

End point description

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 16

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 2	-1.35 ± 0.14	-2.02 ± 0.14	-1.69 ± 0.14
Change at Week 4	-1.78 ± 0.15	-2.57 ± 0.15	-2.56 ± 0.15
Change at Week 8	-1.84 ± 0.15	-2.47 ± 0.15	-2.61 ± 0.15
Change at Week 12	-2.19 ± 0.17	-2.91 ± 0.16	-2.96 ± 0.16
Change at Week 16	-2.10 ± 0.17	-2.69 ± 0.17	-2.69 ± 0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

-0.4

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0149

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-0.61

upper limit

-0.07

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

-0.32

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

-0.47

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

-0.44

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.17

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 32

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 32

End point description

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=281, 282, 284)	6.59 ± 0.94	6.70 ± 0.94	6.60 ± 0.89
Change at Week 32 (n=231, 247, 246)	-2.70 ± 2.06	-2.29 ± 1.95	-2.26 ± 2.24

No statistical analyses for this end point

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16

End point description

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. Physical function refers to subjects ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 16

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 2	-1.26 ± 0.14	-1.95 ± 0.14	-1.69 ± 0.14
Change at Week 4	-1.71 ± 0.15	-2.52 ± 0.15	-2.50 ± 0.15
Change at Week 8	-1.76 ± 0.15	-2.38 ± 0.15	-2.52 ± 0.15
Change at Week 12	-2.04 ± 2.16	-2.83 ± 0.16	-2.87 ± 0.16
Change at Week 16	-2.02 ± 0.17	-2.68 ± 0.16	-2.69 ± 0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

-0.42

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0014

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.17

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

-0.53

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

-0.51

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

-0.33

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

-0.47

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

-0.46

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.82

Confidence interval

level

95%

sides

2-sided

lower limit

-1.15

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

-0.34

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.17

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 32

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 32

End point description

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. Physical function refers to subject’s ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function. The ITT population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=281, 282, 284)	6.59 ± 0.94	6.70 ± 0.94	6.60 ± 0.89
Change at Week 32 (n= 231, 247, 246)	-2.70 ± 2.06	-2.29 ± 1.95	-2.26 ± 2.24

No statistical analyses for this end point

Secondary: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16

Top of page

End point title

Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16

End point description

PGA of OA was assessed by asking a question from subjects: “Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" subjects responded on a scale ranging from 1-5, where 1=very good (no symptom 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 and inability to carry out all normal activities). The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12 and 16

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 2	-0.50 ± 0.05	-0.73 ± 0.05	-0.67 ± 0.05
Change at Week 4	-0.60 ± 0.05	-0.85 ± 0.05	-0.93 ± 0.05
Change at Week 8	-0.62 ± 0.05	-0.79 ± 0.05	-0.88 ± 0.05
Change at Week 12	-0.71 ± 0.06	-0.99 ± 0.06	-1.03 ± 0.06
Change at Week 16	-0.64 ± 0.06	-0.78 ± 0.06	-0.90 ± 0.06

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.05

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.05

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

-0.14

Variability estimate

Standard error of the mean

Dispersion value

0.05

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.05

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0029

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.06

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.15

Variability estimate

Standard error of the mean

Dispersion value

0.06

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.17

Variability estimate

Standard error of the mean

Dispersion value

0.06

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.06

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0352

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

-0.01

Variability estimate

Standard error of the mean

Dispersion value

0.06

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline PGA of osteoarthritis and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.06

Secondary: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 32

Top of page

End point title

Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 32

End point description

PGA of OA was assessed by asking a question from subjects: “Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Subjects responded on a scale ranging from 1-5, where 1=very good (no symptom 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 and inability to carry out all normal activities). Higher scores indicated worse condition. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 281, 282, 284)	3.55 ± 0.62	3.61 ± 0.62	3.56 ± 0.63
Change at Week 32 (n= 231, 247, 246)	-0.84 ± 0.87	-0.64 ± 0.88	-0.63 ± 0.91

No statistical analyses for this end point

Secondary: Percentage of Subjects Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index

Top of page

End point title

Percentage of Subjects Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index

End point description

Subjects were considered as OMERACT-OARSI responders:if the change (improvement) from baseline to week of interest was greater than or equal to (>=)50 percent(%) and >=2 units in either WOMAC pain subscale/physical function subscale score; if change (improvement) from baseline to week of interest was >=20% and >=1 unit in at least 2 of the following:1)WOMAC pain subscale: assess amount of pain experienced (score:0[no pain] to 10[extreme pain], higher score=more pain), 2)WOMAC physical function subscale: assess degree of difficulty experienced (score:0[minimum difficulty] to 10[extreme difficulty], higher score=worse physical function) and 3)PGA of OA: (score:1[very good] to 5[very poor], higher score=worse condition). Missing data was imputed using mixed baseline/last observation carried forward (BOCF/LOCF). ITT population. ‘number of subjects analysed’(N)=subjects who were evaluable for this endpoint; ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24 and 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	281	282	284
Units: percentage of subjects
number (not applicable)
Week 2 (n= 281, 282, 284)	44.1	63.1	54.9
Week 4 (n= 281, 282, 284)	53.0	74.8	71.8
Week 8 (n= 281, 282, 284)	61.9	75.5	75.4
Week 12 (n= 281, 282, 284)	68.7	80.9	81.0
Week 16 (n= 281, 282, 284)	64.4	78.7	76.1
Week 24 (n= 281, 282, 284)	65.1	76.2	77.1
Week 32 (n= 231, 247, 246)	74.0	66.4	63.0

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Odds ratio and 95 percent (%) confidence interval (CI) estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.23

Confidence interval

level

95%

sides

2-sided

lower limit

1.59

upper limit

3.14

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0085

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

2.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.71

Confidence interval

level

95%

sides

2-sided

lower limit

1.89

upper limit

3.88

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.31

Confidence interval

level

95%

sides

2-sided

lower limit

1.62

upper limit

3.28

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.91

Confidence interval

level

95%

sides

2-sided

lower limit

1.33

upper limit

2.75

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

1.32

upper limit

2.73

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0009

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.94

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

2.86

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.95

Confidence interval

level

95%

sides

2-sided

lower limit

1.32

upper limit

2.89

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.06

Confidence interval

level

95%

sides

2-sided

lower limit

1.41

upper limit

3.01

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.78

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

2.57

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0032

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.21

upper limit

2.54

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0013

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.69

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24

Top of page

End point title

Percentage of Subjects With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24

End point description

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint during past 48 hours, calculated as the mean of scores from 5 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0(no pain) to 10(extreme pain), where higher scores=higher pain. Percentage of subjects with cumulative reduction (as percent) (>0% ; >= 10, 20, 30, 40, 50, 60, 70, 80, 90%; =100%) in WOMAC pain subscale from Baseline to Weeks 16 and 24 were reported, subjects (%) are reported more than once in categories specified. Missing data was imputed using mixed BOCF/LOCF. ITT population. Here, ‘N’=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	281	282	284
Units: percentage of subjects
number (not applicable)
Week 16: >0%	81.9	91.8	89.4
Week 16: >=10%	77.6	87.6	82.0
Week 16: >=20%	66.9	79.4	76.1
Week 16: >=30%	56.2	68.1	68.7
Week 16: >=40%	45.2	57.8	59.9
Week 16: >=50%	35.9	49.6	47.5
Week 16: >=60%	27.0	34.4	36.6
Week 16: >=70%	17.1	22.3	24.3
Week 16: >=80%	10.0	14.5	14.4
Week 16: >=90%	3.2	7.4	4.9
Week 16: =100%	1.1	1.8	3.2
Week 24: >0%	80.1	89.7	88.4
Week 24: >=10%	70.8	83.0	83.5
Week 24: >=20%	65.8	76.2	76.8
Week 24: >=30%	56.6	65.6	68.7
Week 24: >=40%	44.8	55.0	59.2
Week 24: >=50%	33.8	45.4	47.9
Week 24: >=60%	24.9	33.3	36.6
Week 24: >=70%	17.8	21.3	23.2
Week 24: >=80%	11.4	12.1	14.1
Week 24: >=90%	3.2	5.3	6.0
Week 24: =100%	1.1	0.7	2.8

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response

Top of page

End point title

Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response

End point description

Percentage of subjects with reduction in WOMAC pain intensity of at least (>=) 30%, 50%, 70% and 90% at Weeks 2, 4, 8, 12, 16, 24 and 32 compared to baseline were classified as responders to WOMAC pain subscale and are reported here. WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. Missing data was imputed using mixed BOCF/LOCF. ITT population. ‘N’=subjects who were evaluable for this endpoint and ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24 and 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	281	282	284
Units: percentage of subjects
number (not applicable)
Week 2: At least 30% reduction (n=281, 282, 284)	33.5	46.8	42.6
Week 2: At least 50% reduction (n=281, 282, 284)	16.7	27.7	18.3
Week 2: At least 70% reduction (n=281, 282, 284)	5.0	10.3	6.7
Week 2: At least 90% reduction (n=281, 282, 284)	1.1	2.5	1.4
Week 4: At least 30% reduction (n=281, 282, 284)	45.2	61.3	58.8
Week 4: At least 50% reduction (n=281, 282, 284)	22.8	33.0	37.7
Week 4: At least 70% reduction (n=281, 282, 284)	8.5	13.1	15.8
Week 4: At least 90% reduction (n=281, 282, 284)	1.4	3.9	4.9
Week 8: At least 30% reduction (n=281, 282, 284)	50.5	64.2	61.6
Week 8: At least 50% reduction (n=281, 282, 284)	26.0	37.2	44.4
Week 8: At least 70% reduction (n=281, 282, 284)	10.7	15.2	22.2
Week 8: At least 90% reduction (n=281, 282, 284)	2.1	4.3	5.6
Week 12: At least 30% reduction (n=281, 282, 284)	58.4	71.6	71.1
Week 12: At least 50% reduction (n=281, 282, 284)	33.8	46.8	50.7
Week 12: At least 70% reduction (n=281, 282, 284)	15.7	24.1	23.2
Week 12: At least 90% reduction (n=281, 282, 284)	1.8	8.5	7.0
Week 16: At least 30% reduction (n=281, 282, 284)	56.2	68.1	68.7
Week 16: At least 50% reduction (n=281, 282, 284)	35.9	49.6	47.5
Week 16: At least 70% reduction (n=281, 282, 284)	17.1	22.3	24.3
Week 16: At least 90% reduction (n=281, 282, 284)	3.2	7.4	4.9
Week 24: At least 30% reduction (n=281, 282, 284)	56.6	65.6	68.7
Week 24: At least 50% reduction (n=281, 282, 284)	33.8	45.4	47.9
Week 24: At least 70% reduction (n=281, 282, 284)	17.8	21.3	23.2
Week 24: At least 90% reduction (n=281, 282, 284)	3.2	5.3	6.0
Week 32: At least 30% reduction (n=231, 247, 246)	65.4	54.7	57.3
Week 32: At least 50% reduction (n=231, 247, 246)	43.7	32.8	32.9
Week 32: At least 70% reduction (n=231, 247, 246)	21.2	12.1	15.4
Week 32: At least 90% reduction (n=231, 247, 246)	4.8	1.6	4.9

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2, >=30%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.83

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

2.59

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

1.08

upper limit

2.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2, >=50%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.03

Confidence interval

level

95%

sides

2-sided

lower limit

1.34

upper limit

3.07

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5118

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.8

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2, >=70%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0093

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.45

Confidence interval

level

95%

sides

2-sided

lower limit

1.25

upper limit

4.81

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3017

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

3.01

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2, >=90%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.216

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

9.58

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7174

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

6.08

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4, >=30%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.04

Confidence interval

level

95%

sides

2-sided

lower limit

1.45

upper limit

2.87

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.81

Confidence interval

level

95%

sides

2-sided

lower limit

1.29

upper limit

2.54

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4, >=50%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0024

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.81

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

2.65

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.17

Confidence interval

level

95%

sides

2-sided

lower limit

1.49

upper limit

3.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4, >=70%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0373

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

3.14

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0046

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.17

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

3.72

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4, >=90%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0683

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

9.47

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0214

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.77

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

11.66

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8, >=30%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.83

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

2.58

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0048

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.63

Confidence interval

level

95%

sides

2-sided

lower limit

1.16

upper limit

2.28

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8, >=50%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0012

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.84

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.65

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.68

upper limit

3.47

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8, >=70%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0537

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

2.74

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.55

Confidence interval

level

95%

sides

2-sided

lower limit

1.58

upper limit

4.13

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8, >=90%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1155

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

6.27

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0271

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.13

upper limit

7.96

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12, >=30%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

2.63

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0011

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

2.56

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12, >=50%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0009

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.79

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.52

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.07

Confidence interval

level

95%

sides

2-sided

lower limit

1.47

upper limit

2.91

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12, >=70%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0064

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.81

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

2.78

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.68

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

2.58

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12, >=90%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.61

Confidence interval

level

95%

sides

2-sided

lower limit

2.09

upper limit

15.08

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0034

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.46

Confidence interval

level

95%

sides

2-sided

lower limit

1.64

upper limit

12.13

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16, >=30%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

2.44

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0014

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

1.25

upper limit

2.5

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16, >=50%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.87

Confidence interval

level

95%

sides

2-sided

lower limit

1.33

upper limit

2.64

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.68

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

2.36

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16, >=70%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0754

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.47

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

2.24

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0253

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

2.44

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16, >=90%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0098

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.98

Confidence interval

level

95%

sides

2-sided

lower limit

1.3

upper limit

6.83

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.223

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

4.13

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24, >=30%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0201

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

2.12

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0021

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

2.44

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24, >=50%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

2.43

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.87

Confidence interval

level

95%

sides

2-sided

lower limit

1.32

upper limit

2.64

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24, >=70%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2031

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

2.01

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0867

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

2.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24, >=90%: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1746

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

4.22

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1039

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

4.57

Secondary: Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response

Top of page

End point title

Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response

End point description

Percentage of subjects with reduction in WOMAC physical function of at least(>=)30,50,70,90% at weeks 2,4,8,12,16,24,32 compared to baseline were classified as responders.WOMAC:Self-administered,disease-specific questionnaire assesses clinically important, subject-relevant symptoms for pain,stiffness and physical function. Physical function:Subject’s ability to move around and perform usual activities of daily living. Physical function subscale17-item questionnaire assesses the degree of difficulty experienced due to OA in index joint(knee/hip) during past 48 hrs,calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and physical subscale on NRS ranged 0(no difficulty) to 10(extreme difficulty),higher scores=extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.ITT population. ‘N’=subjects who were evaluable for this endpoint; ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24 and 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	281	282	284
Units: percentage of subjects
number (not applicable)
Week 2: At least 30% reduction (n= 281, 282, 284)	30.2	44.3	38.7
Week 2: At least 50% reduction (n= 281, 282, 284)	14.6	19.1	18.3
Week 2: At least 70% reduction (n= 281, 282, 284)	3.9	9.2	5.3
Week 2: At least 90% reduction (n= 281, 282, 284)	1.1	2.5	1.8
Week 4: At least 30% reduction (n= 281, 282, 284)	36.3	55.0	53.9
Week 4: At least 50% reduction (n= 281, 282, 284)	18.1	28.0	32.4
Week 4: At least 70% reduction (n= 281, 282, 284)	6.4	11.7	12.0
Week 4: At least 90% reduction (n= 281, 282, 284)	1.1	2.8	4.6
Week 8: At least 30% reduction (n= 281, 282, 284)	45.6	57.4	59.2
Week 8: At least 50% reduction (n= 281, 282, 284)	22.8	33.7	37.3
Week 8: At least 70% reduction (n= 281, 282, 284)	7.5	16.0	15.5
Week 8: At least 90% reduction (n= 281, 282, 284)	1.4	5.0	4.9
Week 12: At least 30% reduction (n= 281, 282, 284)	51.2	67.4	69.4
Week 12: At least 50% reduction (n= 281, 282, 284)	27.8	43.6	43.7
Week 12: At least 70% reduction (n= 281, 282, 284)	12.8	19.9	21.1
Week 12: At least 90% reduction (n= 281, 282, 284)	0.7	6.7	5.6
Week 16: At least 30% reduction (n= 281, 282, 284)	53.0	65.2	66.2
Week 16: At least 50% reduction (n= 281, 282, 284)	32.0	42.9	44.0
Week 16: At least 70% reduction (n= 281, 282, 284)	14.2	21.3	18.3
Week 16: At least 90% reduction (n= 281, 282, 284)	2.5	6.0	6.0
Week 24: At least 30% reduction (n= 281, 282, 284)	51.2	64.9	68.7
Week 24: At least 50% reduction (n= 281, 282, 284)	32.4	41.5	44.7
Week 24: At least 70% reduction (n= 281, 282, 284)	14.6	19.1	17.3
Week 24: At least 90% reduction (n= 281, 282, 284)	1.8	5.3	5.3
Week 32: At least 30% reduction (n= 231, 247, 246)	60.2	51.4	53.7
Week 32: At least 50% reduction (n= 231, 247, 246)	40.3	31.2	30.5
Week 32: At least 70% reduction (n= 231, 247, 246)	16.9	11.7	11.4
Week 32: At least 90% reduction (n= 231, 247, 246)	3.5	2.0	3.3

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2, >=30%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.89

Confidence interval

level

95%

sides

2-sided

lower limit

1.33

upper limit

2.68

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0286

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

2.1

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2, >=50%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1031

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

2.27

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2033

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.34

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

2.1

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2, >=70%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0064

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.34

upper limit

5.86

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3706

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

3.23

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2, >=90%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2121

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.39

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

9.41

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4859

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

7.11

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4, >=30%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.25

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

3.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

2.96

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4, >=50%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.91

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.87

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.28

Confidence interval

level

95%

sides

2-sided

lower limit

1.53

upper limit

3.4

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4, >=70%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0107

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.23

Confidence interval

level

95%

sides

2-sided

lower limit

1.21

upper limit

4.14

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0126

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.18

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

4.02

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4, >=90%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1516

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

10.26

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.49

Confidence interval

level

95%

sides

2-sided

lower limit

1.25

upper limit

16.05

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8, >=30%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0034

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

2.31

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

2.45

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8, >=50%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0014

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.86

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.71

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.46

upper limit

3.1

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8, >=70%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.49

upper limit

4.55

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.39

upper limit

4.24

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8, >=90%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

12.79

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0211

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.79

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

11.78

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12, >=30%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.01

Confidence interval

level

95%

sides

2-sided

lower limit

1.43

upper limit

2.84

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.19

Confidence interval

level

95%

sides

2-sided

lower limit

1.55

upper limit

3.1

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12, >=50%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.47

upper limit

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

1.46

upper limit

2.96

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12, >=70%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.74

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

2.76

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0072

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.86

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

2.94

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12, >=90%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0015

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

10.84

Confidence interval

level

95%

sides

2-sided

lower limit

2.49

upper limit

47.22

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0044

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

8.62

Confidence interval

level

95%

sides

2-sided

lower limit

1.96

upper limit

37.96

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16, >=30%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

2.43

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0011

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

1.26

upper limit

2.5

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16, >=50%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0035

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.68

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

2.38

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0022

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

2.43

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16, >=70%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0155

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.74

Confidence interval

level

95%

sides

2-sided

lower limit

1.11

upper limit

2.72

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1549

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.39

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

2.2

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16, >=90%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0212

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.94

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

7.37

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0373

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.06

upper limit

6.57

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24, >=30%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.83

Confidence interval

level

95%

sides

2-sided

lower limit

1.29

upper limit

2.57

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.51

upper limit

3.02

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24, >=50%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0152

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.54

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

2.18

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0018

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

2.45

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24, >=70%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.097

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.47

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

2.31

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3435

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.98

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24, >=90%: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC physical function subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0236

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

9.27

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0296

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.14

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

8.81

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24

Top of page

End point title

Percentage of Subjects With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24

End point description

Percentage of subjects with cumulative reduction (as percent) (>0; >=10, 20, 30, 40, 50, 60, 70, 80 and 90; =100 %) in WOMAC physical function subscale from Baseline to Weeks 16 and 24 were reported. WOMAC:Self-administered, disease-specific questionnaire assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. Physical function:subjects ability to move around and perform usual activities of daily living. WOMAC physical function subscale:17-item questionnaire to assess the degree of difficulty experienced due to OA in index joint(knee or hip) during past 48 hrs, calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale on NRS ranged 0(no difficulty) to 10(extreme difficulty), higher scores=extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF. ITT population. Here ‘N’=subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	281	282	284
Units: percentage of subjects
number (not applicable)
Week 16: >=0%	84.7	93.6	93.0
Week 16: >=10%	75.1	87.2	83.8
Week 16: >=20%	61.6	73.8	73.9
Week 16: >=30%	53.0	65.2	66.2
Week 16: >=40%	44.1	55.3	56.0
Week 16: >=50%	32.0	42.9	44.0
Week 16: >=60%	20.3	30.1	30.3
Week 16: >=70%	14.2	21.3	18.3
Week 16: >=80%	7.1	12.4	11.3
Week 16: >=90%	2.5	6.0	6.0
Week 16: =100%	0.7	0.7	1.8
Week 24: >=0%	79.7	89.0	90.1
Week 24: >=10%	70.1	85.8	84.2
Week 24: >=20%	61.6	74.8	78.2
Week 24: >=30%	51.2	64.9	68.7
Week 24: >=40%	41.3	51.1	57.0
Week 24: >=50%	32.4	41.5	44.7
Week 24: >=60%	21.0	30.9	30.6
Week 24: >=70%	14.6	19.1	17.3
Week 24: >=80%	6.4	10.6	10.2
Week 24: >=90%	1.8	5.3	5.3
Week 24: =100%	0	0.4	1.8

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis

Top of page

End point title

Percentage of Subjects Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis

End point description

PGA of OA was assessed by asking a question from subjects: “Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today?" Subjects responded on a scale ranging from 1-5, where, 1=very good (no symptom 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 and inability to carry out all normal activities). Higher scores indicated worse condition. Percentage of subjects with improvement of at least 2 points from Baseline in PGA of OA were reported. Missing data was imputed using mixed BOCF/LOCF. ITT population. Here ‘N’=subjects who were evaluable for this endpoint and ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16, 24 and 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	281	282	284
Units: percentage of subjects
number (not applicable)
Week 2 (n=281, 282, 284)	8.5	15.6	12.0
Week 4 (n=281, 282, 284)	8.5	17.7	19.0
Week 8 (n=281, 282, 284)	12.8	21.3	21.8
Week 12 (n=281, 282, 284)	14.6	26.2	28.5
Week 16 (n=281, 282, 284)	14.6	22.7	27.1
Week 24 (n=281, 282, 284)	17.4	24.1	25.7
Week 32 (n=231, 247, 246)	19.9	14.2	15.4

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline patient global assessment of osteoarthritis scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0132

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.14

Confidence interval

level

95%

sides

2-sided

lower limit

1.17

upper limit

3.9

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1274

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

3.02

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline patient global assessment of osteoarthritis scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0016

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.62

Confidence interval

level

95%

sides

2-sided

lower limit

1.44

upper limit

4.76

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.34

Confidence interval

level

95%

sides

2-sided

lower limit

1.84

upper limit

6.03

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline patient global assessment of osteoarthritis scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0089

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.04

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

3.49

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0012

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.42

upper limit

4.1

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline patient global assessment of osteoarthritis scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.45

upper limit

3.98

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.16

Confidence interval

level

95%

sides

2-sided

lower limit

1.92

upper limit

5.21

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline patient global assessment of osteoarthritis scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0203

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.83

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

3.06

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.94

Confidence interval

level

95%

sides

2-sided

lower limit

1.77

upper limit

4.86

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Odds ratio and 95% CI estimated from logistic regression model. Logistic regression model included baseline patient global assessment of osteoarthritis scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

563

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0775

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

2.55

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0064

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.97

Confidence interval

level

95%

sides

2-sided

lower limit

1.21

upper limit

3.21

Secondary: Change From Baseline for Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24

Top of page

End point title

Change From Baseline for Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24

End point description

Subjects assessed their average pain in the index hip/knee in the past 24 hours using a scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicated higher pain. Data represents averages of the values reported during the 8-week interval up to and including the given week. Change from baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 1	-0.57 ± 0.11	-1.06 ± 0.11	-0.93 ± 0.11
Change at Week 2	-0.98 ± 0.14	-1.72 ± 0.14	-1.49 ± 0.14
Change at Week 3	-1.19 ± 0.15	-1.97 ± 0.15	-1.67 ± 0.15
Change at Week 4	-1.37 ± 0.15	-2.28 ± 0.15	-2.13 ± 0.15
Change at Week 6	-1.48 ± 0.16	-2.38 ± 0.16	-2.43 ± 0.16
Change at Week 8	-1.57 ± 0.16	-2.19 ± 0.16	-2.39 ± 0.16
Change at Week 10	-1.79 ± 0.17	-2.51 ± 0.17	-2.56 ± 0.17
Change at Week 12	-1.84 ± 0.17	-2.57 ± 0.17	-2.64 ± 0.17
Change at Week 16	-1.98 ± 0.18	-2.50 ± 0.17	-2.61 ± 0.17
Change at Week 20	-2.17 ± 0.18	-2.87 ± 0.18	-2.86 ± 0.18
Change at Week 24	-2.21 ± 0.19	-2.60 ± 0.18	-2.73 ± 0.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 1: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.11

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0009

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

-0.15

Variability estimate

Standard error of the mean

Dispersion value

0.11

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

-0.48

Variability estimate

Standard error of the mean

Dispersion value

0.13

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

-0.25

Variability estimate

Standard error of the mean

Dispersion value

0.13

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 3: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.49

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

-0.21

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.91

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

-0.62

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

-0.47

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 6: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

-0.59

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.95

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

-0.64

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-0.93

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 10: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

-0.44

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

-0.46

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

-0.16

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 20: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.06

upper limit

-0.33

Variability estimate

Standard error of the mean

Dispersion value

0.19

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.68

Confidence interval

level

95%

sides

2-sided

lower limit

-1.05

upper limit

-0.32

Variability estimate

Standard error of the mean

Dispersion value

0.19

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0506

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.2

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0086

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.52

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.2

Secondary: Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32

Top of page

End point title

Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 28 and 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=278, 280, 280)	6.79 ± 1.56	7.03 ± 1.38	6.90 ± 1.43
Change at Week 28 (n=239, 260, 254)	-2.26 ± 2.27	-2.63 ± 2.32	-2.58 ± 2.33
Change at Week 32 (n=226, 250, 245)	-2.19 ± 2.40	-2.07 ± 2.33	-2.13 ± 2.40

No statistical analyses for this end point

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24

End point description

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee or hip) during the past 48 hours. It was calculated as the mean of scores from 2 individual questions scored on NRS. Scores for each question and WOMAC stiffness subscale score on NRS ranged from 0 (no stiffness) to 10 (extreme stiffness), where higher scores indicated higher stiffness. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 2	-1.25 ± 0.15	-2.03 ± 0.15	-1.90 ± 0.15
Change at Week 4	-1.90 ± 0.16	-2.62 ± 0.16	-2.74 ± 0.16
Change at Week 8	-1.82 ± 0.17	-2.41 ± 0.17	-2.81 ± 0.17
Change at Week 12	-2.10 ± 0.18	-2.90 ± 0.17	-2.95 ± 0.17
Change at Week 16	-2.00 ± 0.18	-2.65 ± 0.18	-2.77 ± 0.18
Change at Week 24	-1.97 ± 0.19	-2.59 ± 0.19	-2.84 ± 0.19

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

-0.48

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

-0.41

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.15

upper limit

-0.53

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

upper limit

-0.26

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

-0.67

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.14

upper limit

-0.46

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.18

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.12

upper limit

-0.43

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0013

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

-0.24

Variability estimate

Standard error of the mean

Dispersion value

0.19

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC stiffness subscales and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.19

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 32

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 32

End point description

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee or hip) during the past 48 hours. It was calculated as the mean of scores from 2 individual questions scored on a NRS. Scores for each question and WOMAC stiffness subscale score on NRS ranged from 0 (no stiffness) to 10 (extreme stiffness), where higher scores indicated higher stiffness. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=281, 282, 284)	6.46 ± 1.43	6.44 ± 1.59	6.44 ± 1.53
Change at Week 32 (n=231, 247, 246)	-2.57 ± 2.22	-2.34 ± 2.18	-2.31 ± 2.51

No statistical analyses for this end point

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24

End point description

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [extreme stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher scores indicated worse response. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 2	-1.28 ± 0.13	-1.99 ± 0.13	-1.75 ± 0.13
Change at Week 4	-1.80 ± 0.14	-2.57 ± 0.14	-2.60 ± 0.14
Change at Week 8	-1.81 ± 0.15	-2.42 ± 0.15	-2.65 ± 0.15
Change at Week 12	-2.11 ± 0.16	-2.89 ± 0.16	-2.92 ± 0.16
Change at Week 16	-2.04 ± 0.17	-2.67 ± 0.17	-2.71 ± 0.16
Change at Week 24	-2.11 ± 0.17	-2.66 ± 0.17	-2.83 ± 0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

-0.45

Variability estimate

Standard error of the mean

Dispersion value

0.13

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0004

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

-0.21

Variability estimate

Standard error of the mean

Dispersion value

0.13

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

-0.49

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

-0.53

Variability estimate

Standard error of the mean

Dispersion value

0.14

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.32

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.84

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

-0.56

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.78

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

-0.47

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-1.12

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

-0.35

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0015

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.55

Confidence interval

level

95%

sides

2-sided

lower limit

-0.89

upper limit

-0.21

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC average scores and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.17

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 32

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 32

End point description

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [extreme stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher scores indicated worse response. ITT population. Here, ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=281, 282, 284)	6.57 ± 0.90	6.63 ± 0.96	6.60 ± 0.91
Change at Week 32 (n= 231, 247, 246)	-2.61 ± 1.96	-2.28 ± 1.87	-2.27 ± 2.12

No statistical analyses for this end point

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Weeks 2, 4, 8, 12, 16 and 24

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Weeks 2, 4, 8, 12, 16 and 24

End point description

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA in index joint (knee or hip). Subjects answered a question: "How much pain have you had when walking on a flat surface?”. Subjects responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 2	-1.27 ± 0.14	-1.94 ± 0.14	-1.64 ± 0.14
Change at Week 4	-1.69 ± 0.15	-2.51 ± 0.15	-2.54 ± 0.15
Change at Week 8	-1.77 ± 0.16	-2.36 ± 0.15	-2.49 ± 0.15
Change at Week 12	-2.17 ± 0.17	-2.91 ± 0.16	-2.97 ± 0.16
Change at Week 16	-2.06 ± 0.18	-2.68 ± 0.17	-2.66 ± 0.17
Change at Week 24	-2.21 ± 0.18	-2.61 ± 0.17	-2.80 ± 0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

-0.38

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0139

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-0.67

upper limit

-0.08

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.82

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

-0.51

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.86

Confidence interval

level

95%

sides

2-sided

lower limit

-1.16

upper limit

-0.55

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

-0.4

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-1.14

upper limit

-0.44

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0009

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

-0.25

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0377

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

-0.02

Variability estimate

Standard error of the mean

Dispersion value

0.19

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0019

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.59

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.19

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 32

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 32

End point description

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA in index joint (knee or hip). Subjects answered a question: "How much pain have you had when walking on a flat surface?”. Subjects responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=281, 282, 284)	6.73 ± 1.25	6.77 ± 1.27	6.79 ± 1.19
Change at Week 32 (n=231, 247, 246)	-2.46 ± 2.24	-2.01 ± 2.10	-1.99 ± 2.49

No statistical analyses for this end point

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Weeks 2, 4, 8, 12, 16 and 24

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Weeks 2, 4, 8, 12, 16 and 24

End point description

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA in index joint (knee or hip). Subjects answered a question: "How much pain have you had when going up or down the stairs?” Subjects responded about the amount of pain they experienced when going up or down stairs by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 2	-1.39 ± 0.15	-2.08 ± 0.15	-1.96 ± 0.15
Change at Week 4	-1.76 ± 0.16	-2.73 ± 0.15	-2.72 ± 0.15
Change at Week 8	-1.72 ± 0.17	-2.49 ± 0.17	-2.74 ± 0.17
Change at Week 12	-2.17 ± 0.18	-2.92 ± 0.18	-3.05 ± 0.18
Change at Week 16	-2.06 ± 0.18	-2.72 ± 0.18	-2.83 ± 0.18
Change at Week 24	-2.32 ± 0.19	-2.76 ± 0.18	-3.04 ± 0.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.57

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

-0.27

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-1.29

upper limit

-0.65

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-1.28

upper limit

-0.65

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

-0.42

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-1.01

Confidence interval

level

95%

sides

2-sided

lower limit

-1.35

upper limit

-0.67

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.75

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

-0.39

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.87

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

-0.51

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.66

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

-0.29

Variability estimate

Standard error of the mean

Dispersion value

0.19

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.77

Confidence interval

level

95%

sides

2-sided

lower limit

-1.13

upper limit

-0.4

Variability estimate

Standard error of the mean

Dispersion value

0.19

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0246

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.44

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

-0.06

Variability estimate

Standard error of the mean

Dispersion value

0.2

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets includes treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

-0.33

Variability estimate

Standard error of the mean

Dispersion value

0.2

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Week 32

Top of page

End point title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Week 32

End point description

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, subject-relevant symptoms for pain, stiffness and physical function in subjects with OA in index joint (knee or hip). Subject answered a question: "How much pain have you had when going up or down the stairs?” Subjects responded about the amount of pain they experienced when going up or down stairs by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n=281, 282, 284)	7.65 ± 1.13	7.79 ± 1.06	7.66 ± 1.18
Change at Week 32 (n=231, 247, 246)	-2.72 ± 2.32	-2.23 ± 2.09	-2.15 ± 2.41

No statistical analyses for this end point

Secondary: Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline

Top of page

End point title

Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline

End point description

WPAI is 6-question subject rated questionnaire to determine the impact of OA on absenteeism, presenteeism, work productivity, and daily activity impairment for a period of 7 days prior to a visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Percent Work Time Missed (n=81, 76, 72)	9.7 ± 23.46	5.6 ± 18.33	6.9 ± 21.33
Percent Impairment While Working (n=78, 74, 69)	56.5 ± 22.26	58.9 ± 21.81	57.4 ± 18.44
Percent Overall Work Impairment (n=78, 74, 69)	59.3 ± 21.32	60.2 ± 21.20	58.3 ± 18.89
Percent Activity Impairment (n=277, 278, 283)	66.6 ± 13.35	67.7 ± 15.53	67.5 ± 13.26

No statistical analyses for this end point

Secondary: Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24

Top of page

End point title

Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24

End point description

End point type

Secondary

End point timeframe

Baseline, Weeks 8, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
least squares mean (standard error)
Change at Week 8: absenteeism, n=65,62,60	0.04 ± 2.12	1.24 ± 2.12	-2.05 ± 2.11
Change at Week 8: presenteeism, n=64,60,57	-13.57 ± 3.11	-20.26 ± 3.10	-26.26 ± 3.12
Change at Week 8:work productivity, n=64,60,57	-13.78 ± 3.20	-20.53 ± 3.18	-26.26 ± 3.22
Change at Week8:activity Impairment,n=268,272,281	-15.66 ± 1.55	-21.84 ± 1.54	-24.79 ± 1.53
Change at Week 16: absenteeism, n=64,59,51	2.36 ± 2.24	1.74 ± 2.29	-2.16 ± 2.36
Change at Week 16: presenteeism, n=61,58,50	-15.92 ± 3.28	-26.23 ± 3.33	-26.48 ± 3.42
Change at Week 16:work productivity, n=61,58,50	-16.38 ± 3.33	-25.79 ± 3.37	-26.42 ± 3.47
Change at Week16:Activity Impairment,n=254,261,271	-19.15 ± 1.77	-25.16 ± 1.77	-26.13 ± 1.74
Change at Week 24: absenteeism, n=50,57,51	4.09 ± 3.27	2.77 ± 3.18	1.16 ± 3.27
Change at Week 24: presenteeism, n=47,55,48	-15.03 ± 3.86	-19.31 ± 3.50	-17.77 ± 3.74
Change at Week24:work productivity, n=47,55,48	-15.17 ± 3.92	-19.03 ± 3.56	-17.29 ± 3.82
Change at Week24:activity Impairment,n=231,252,254	-21.49 ± 1.84	-24.57 ± 1.79	-26.44 ± 1.79

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Percent Work Time Missed: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6427

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

6.29

Variability estimate

Standard error of the mean

Dispersion value

2.57

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4208

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-2.09

Confidence interval

level

95%

sides

2-sided

lower limit

-7.22

upper limit

3.04

Variability estimate

Standard error of the mean

Dispersion value

2.59

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Percent Work Time Missed: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8204

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.62

Confidence interval

level

95%

sides

2-sided

lower limit

-6.03

upper limit

4.79

Variability estimate

Standard error of the mean

Dispersion value

2.73

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1157

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-4.52

Confidence interval

level

95%

sides

2-sided

lower limit

-10.16

upper limit

1.13

Variability estimate

Standard error of the mean

Dispersion value

2.85

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Percent Work Time Missed: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5845

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-1.32

Confidence interval

level

95%

sides

2-sided

lower limit

-6.12

upper limit

3.47

Variability estimate

Standard error of the mean

Dispersion value

2.41

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2514

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-2.93

Confidence interval

level

95%

sides

2-sided

lower limit

-7.97

upper limit

2.11

Variability estimate

Standard error of the mean

Dispersion value

2.54

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Percent Impairment While Working: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0717

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-6.68

Confidence interval

level

95%

sides

2-sided

lower limit

-13.97

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

3.67

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-12.69

Confidence interval

level

95%

sides

2-sided

lower limit

-20.11

upper limit

-5.26

Variability estimate

Standard error of the mean

Dispersion value

3.74

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Percent Impairment While Working: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0079

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-10.31

Confidence interval

level

95%

sides

2-sided

lower limit

-17.85

upper limit

-2.77

Variability estimate

Standard error of the mean

Dispersion value

3.8

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0096

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-10.56

Confidence interval

level

95%

sides

2-sided

lower limit

-18.49

upper limit

-2.63

Variability estimate

Standard error of the mean

Dispersion value

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Percent Impairment While Working: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3302

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-4.28

Confidence interval

level

95%

sides

2-sided

lower limit

-12.97

upper limit

4.41

Variability estimate

Standard error of the mean

Dispersion value

4.37

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5483

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-2.74

Confidence interval

level

95%

sides

2-sided

lower limit

-11.78

upper limit

6.3

Variability estimate

Standard error of the mean

Dispersion value

4.54

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Percent Overall Work Impairment: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0774

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-6.75

Confidence interval

level

95%

sides

2-sided

lower limit

-14.26

upper limit

0.76

Variability estimate

Standard error of the mean

Dispersion value

3.79

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0017

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-12.48

Confidence interval

level

95%

sides

2-sided

lower limit

-20.15

upper limit

-4.81

Variability estimate

Standard error of the mean

Dispersion value

3.87

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Percent Overall Work Impairment: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0135

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-9.41

Confidence interval

level

95%

sides

2-sided

lower limit

-16.83

upper limit

-1.99

Variability estimate

Standard error of the mean

Dispersion value

3.74

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0129

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-10.04

Confidence interval

level

95%

sides

2-sided

lower limit

-17.91

upper limit

-2.17

Variability estimate

Standard error of the mean

Dispersion value

3.97

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Percent Overall Work Impairment: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3869

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-3.85

Confidence interval

level

95%

sides

2-sided

lower limit

-12.66

upper limit

4.96

Variability estimate

Standard error of the mean

Dispersion value

4.43

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6485

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-2.11

Confidence interval

level

95%

sides

2-sided

lower limit

-11.31

upper limit

7.08

Variability estimate

Standard error of the mean

Dispersion value

4.62

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Percent Activity Impairment: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-6.18

Confidence interval

level

95%

sides

2-sided

lower limit

-9.34

upper limit

-3.03

Variability estimate

Standard error of the mean

Dispersion value

1.61

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-9.13

Confidence interval

level

95%

sides

2-sided

lower limit

-12.26

upper limit

-6

Variability estimate

Standard error of the mean

Dispersion value

1.6

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Percent Activity Impairment: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-9.51

upper limit

-2.5

Variability estimate

Standard error of the mean

Dispersion value

1.79

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-6.97

Confidence interval

level

95%

sides

2-sided

lower limit

-10.44

upper limit

-3.51

Variability estimate

Standard error of the mean

Dispersion value

1.77

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Percent Activity Impairment: WPAI parameters were analysed using ANCOVA model which included covariates of the corresponding baseline score, baseline diary average pain, index joint, highest Kellgren-Lawrence grade (2, 3 or 4), and treatment, with study site as a random effect.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1004

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-3.08

Confidence interval

level

95%

sides

2-sided

lower limit

-6.76

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

1.87

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0079

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-4.94

Confidence interval

level

95%

sides

2-sided

lower limit

-8.59

upper limit

-1.3

Variability estimate

Standard error of the mean

Dispersion value

1.86

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

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End point title

European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score

End point description

EQ-5D-5L is a standardized subject completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The health utility score for a subject with no problems in all 5 items is 1 for all countries (except for Zimbabwe where it is 0.9), and is reduced where a subject reports greater levels of problems across the five dimensions. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 8, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline: Mobility (n=277, 278, 283)	3.1 ± 0.63	3.1 ± 0.62	3.2 ± 0.65
Baseline: Self-care (n=277, 278, 283)	2.4 ± 0.92	2.3 ± 0.92	2.3 ± 0.90
Baseline: Usual activities (n=277, 278, 283)	3.0 ± 0.65	3.0 ± 0.68	3.0 ± 0.68
Baseline: Pain/Discomfort (n=277, 278, 283)	3.3 ± 0.72	3.2 ± 0.73	3.3 ± 0.69
Baseline: Anxiety/Depression (n=277, 278, 283)	1.7 ± 0.87	1.7 ± 0.88	1.7 ± 0.87
Week 8: Mobility (n=273, 276, 282)	2.6 ± 0.82	2.3 ± 0.83	2.3 ± 0.80
Week 8: Self-care (n=273, 276, 282)	2.0 ± 0.90	1.8 ± 0.80	1.6 ± 0.78
Week 8: Usual activities (n=273, 276, 282)	2.5 ± 0.78	2.3 ± 0.82	2.2 ± 0.78
Week 8: Pain/Discomfort (n=273, 276, 282)	2.7 ± 0.85	2.5 ± 0.80	2.4 ± 0.79
Week 8: Anxiety/Depression (n=273, 276, 282)	1.5 ± 0.80	1.4 ± 0.64	1.4 ± 0.71
Week 16: Mobility (n=259, 266 and 271)	2.4 ± 0.88	2.2 ± 0.84	2.2 ± 0.84
Week 16: Self-care (n=259, 266, 271)	1.8 ± 0.88	1.7 ± 0.78	1.6 ± 0.80
Week 16: Usual activities (n=259, 266, 272)	2.3 ± 0.81	2.2 ± 0.78	2.1 ± 0.84
Week 16: Pain/Discomfort (n=259, 266, 271)	2.5 ± 0.82	2.3 ± 0.80	2.3 ± 0.80
Week 16: Anxiety/Depression (n=259, 266, 271)	1.4 ± 0.78	1.3 ± 0.61	1.4 ± 0.68
Week 24: Mobility (n=236, 257, 255)	2.4 ± 0.78	2.3 ± 0.84	2.3 ± 0.84
Week 24: Self-care (n=236, 257, 255)	1.7 ± 0.83	1.7 ± 0.77	1.6 ± 0.76
Week 24: Usual activities (n=236, 257, 255)	2.3 ± 0.78	2.2 ± 0.82	2.2 ± 0.82
Week 24: Pain/Discomfort (n=236, 257, 255)	2.5 ± 0.81	2.4 ± 0.78	2.4 ± 0.77
Week 24: Anxiety/Depression (n=236, 257, 255)	1.4 ± 0.67	1.4 ± 0.71	1.4 ± 0.68

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

EQ-5D-5L: standardized subject completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Responses from the five domains were used to calculate a single utility index (the Overall health utility score) where values are less than equal to (<=) 1. The Overall health utility score for a subject with no problems in all 5 items is 1 for all countries (except for Zimbabwe where it is 0.9), and is reduced where a subject reports greater levels of problems across the five dimensions. ITT population. Here, ‘n’=subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 8, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 277, 278, 283)	0.57 ± 0.18	0.56 ± 0.18	0.56 ± 0.18
Week 8 (n= 273, 276, 282)	0.67 ± 0.17	0.71 ± 0.16	0.73 ± 0.17
Week 16 (n= 259, 266, 271)	0.70 ± 0.19	0.73 ± 0.15	0.73 ± 0.17
Week 24 (n= 236, 257, 255)	0.70 ± 0.16	0.72 ± 0.16	0.73 ± 0.15

No statistical analyses for this end point

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Reported Treatment Impact Assessment-Overall, How Satisfied Are You With The Drug That You Received in This Study?

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End point title

Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Reported Treatment Impact Assessment-Overall, How Satisfied Are You With The Drug That You Received in This Study?

End point description

The mPRTI is a self-administered questionnaire containing subject reported treatment impact assessment (to assess subject satisfaction), subject global preference assessment (to assess previous treatment and preference to continue using the investigational product) and subject willingness to use drug again assessment. For subject satisfaction, subjects responded using interactive response technology (IRT) on a 5 point likert scale from 1-5, where 1=extremely dissatisfied, 2=dissatisfied, 3=neither satisfied nor dissatisfied, 4=satisfied and 5=extremely satisfied. Higher scores indicated greater satisfaction. Here mPRTI was reported for week (W) 16 and 24. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Weeks 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
W16:extremely satisfied,n=268,270,278	41	65	65
W24:extremely satisfied,n=238,257,255	46	72	66
W16:satisfied,n=268,270,278	109	141	137
W24:satisfied,n=238,257,255	97	119	128
W16:neither satisfied/dissatisfied,n=268,270,278	78	50	63
W24:neither satisfied/dissatisfied,n=238,257,255	64	54	48
W16:dissatisfied,n=268,270,278	31	13	11
W24:dissatisfied,n=238,257,255	28	10	9
W16:extremely dissatisfied,n=268,270,278	9	1	2
W24:extremely dissatisfied,n=238,257,255	3	2	4

No statistical analyses for this end point

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Osteoarthritis Pain Before Enrolling?

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End point title

Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Osteoarthritis Pain Before Enrolling?

End point description

The mPRTI is a self-administered questionnaire containing subject reported treatment impact assessment (to assess subject satisfaction), subject global preference assessment (to assess previous treatment and preference to continue using the investigational product) and subject willingness to use drug again assessment. To assess previous treatment, subjects responded for, 1=injectable prescription medicines, 2=prescription medicines taken by mouth, 3=surgery, 4=prescription medicines and surgery and 5=no treatment. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this end point at specified time point.

End point type

Secondary

End point timeframe

Weeks 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
W 16: Injectable medicines, n=268,270,278	23	34	28
W 24: Injectable medicines, n=238,257,255	16	21	35
W 16: medicines taken by mouth, n=268,270,278	214	212	224
W 24: medicines taken by mouth, n=238,257,255	196	211	196
W 16: surgery, n=268,270,278	5	0	1
W 24: surgery, n=238,257,255	3	0	3
W 16:medicines and surgery, n=268,270,278	8	5	5
W 24:medicines and surgery, n=238,257,255	4	3	4
W 16: No treatment, n=268,270,278	18	19	20
W 24: No treatment, n=238,257,255	19	22	17

No statistical analyses for this end point

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment?

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End point title

Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment?

End point description

The mPRTI is a self-administered questionnaire containing subject reported treatment impact assessment (to assess subject satisfaction), subject global preference assessment (to assess previous (prev) treatment and preference to continue using the investigational product) and subject willingness to use drug again assessment. To assess preference to continue using the investigational product, subjects responded using interactive response technology (IRT) on a 5 point likert scale from 1-5, where, 1= yes, I definitely prefer the drug that I am receiving now, 2= I have a slight preference for the drug that I am receiving now, 3= I have no preference either way, 4= I have a slight preference for my previous treatment, 5= No, I definitely prefer my previous treatment. Higher scores indicate lesser preference to use the investigational product. ITT population. Here, ‘n’=subjects evaluable for this end point at specified time point.

End point type

Secondary

End point timeframe

Weeks 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
W16:definitely prefer study drug,n=268,270,278	106	129	138
W24:definitely prefer study drug,n=238,257,255	87	129	127
W16:slight preference-study drug,n=268,270,278	66	86	83
W24:slight preference-study drug,n=238,257,255	73	79	78
W16:no preference either way,n=268,270,278	65	41	48
W24:no preference either way,n=238,257,255	58	43	36
W16:slight preference-prev treatment,n=268,270,278	14	11	4
W24:slight preference-prev treatment,n=238,257,255	14	4	8
W16:definitely prefer prev treatment,n=268,270,278	17	3	5
W24:definitely prefer prev treatment,n=238,257,255	6	2	6

No statistical analyses for this end point

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Osteoarthritis Pain?

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End point title

Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Osteoarthritis Pain?

End point description

The mPRTI is a self-administered questionnaire containing subject reported treatment impact assessment (to assess subject satisfaction), subject global preference assessment (to assess previous treatment and preference to continue using the investigational product) and subject willingness to use drug again assessment. To assess Patient willingness to use drug again, subjects responded using interactive response technology (IRT) on a 5 point likert scale from 1-5, where, 1= yes, I would definitely want to use the same drug again, 2= I might want to use the same drug again, 3= I am not sure, 4= I might not want to use the same drug again, 5= no, I definitely would not want to use the same drug again. Higher scores indicate lesser willingness to use the investigational product. ITT population. Here, ‘n’=subjects evaluable for this endpoint at specified time point.

End point type

Secondary

End point timeframe

Weeks 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
W16:definitely the same drug again,n=268,270,278	111	144	155
W24:definitely the same drug again,n=238,257,255	101	131	139
W16:might want same drug again,n=268,270,278	67	83	74
W24:might want same drug again,n=238,257,255	62	73	63
W16:I am not sure,n=268,270,278	59	29	41
W24:I am not sure,n=238,257,255	53	43	38
W16:might not want same drug again,n=268,270,278	10	9	5
W24:might not want same drug again,n=238,257,255	13	5	9
W16:definitely not same drug again,n=268,270,278	21	5	3
W24:definitely not same drug again,n=238,257,255	9	5	6

No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis

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End point title

Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis

End point description

Osteoarthritis HCRU assessed healthcare usage during last 3 months (for baseline and week 48) and past 8 weeks (for week 32). Visits of services directly related to osteoarthritis evaluated were: visits to primary care physician, neurologist, rheumatologist, physician assistant (pa) or nurse practitioner, pain specialist, orthopedist, physical therapist, chiropractor, alternative medicine or therapy, podiatrist, nutritionist/dietitian, radiologist, home healthcare services and other practitioner. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n' = subjects evaluable for this endpoint for specified categories.

End point type

Secondary

End point timeframe

Baseline, Weeks 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: visits
median (full range (min-max))
Baseline: Primary Care Physician (n=116, 115, 112)	2.0 (1.0 to 14.0)	2.0 (1.0 to 10.0)	2.0 (1.0 to 7.0)
Baseline: Neurologist (n=4, 7, 5)	1.0 (1.0 to 3.0)	1.0 (1.0 to 100.0)	1.0 (1.0 to 2.0)
Baseline: Rheumatologist (n=82, 99, 89)	2.0 (1.0 to 102.0)	2.0 (1.0 to 11.0)	2.0 (1.0 to 5.0)
Baseline:Pa or nurse Practitioner (n=7, 6, 5)	3.0 (1.0 to 7.0)	2.5 (1.0 to 5.0)	3.0 (3.0 to 8.0)
Baseline: Pain specialist (n=12, 21, 24)	1.0 (1.0 to 3.0)	2.0 (1.0 to 5.0)	1.0 (1.0 to 6.0)
Baseline: Orthopedist (n=84, 83, 85)	2.0 (1.0 to 12.0)	2.0 (1.0 to 12.0)	2.0 (1.0 to 7.0)
Baseline: Physical therapist (n=25, 20, 30)	10.0 (1.0 to 24.0)	3.5 (1.0 to 100.0)	2.5 (1.0 to 60.0)
Baseline: Chiropractor (n=3, 1, 1)	2.0 (1.0 to 3.0)	1.0 (1.0 to 1.0)	2.0 (2.0 to 2.0)
Baseline: Alternative medicine/therapy (n=4, 2, 4)	1.0 (1.0 to 3.0)	2.0 (2.0 to 2.0)	2.5 (1.0 to 4.0)
Baseline: Podiatrist (n=7, 4, 3)	1.0 (1.0 to 2.0)	1.0 (1.0 to 1.0)	3.0 (2.0 to 3.0)
Baseline: Nutritionist/dietitian (n=3, 2, 7)	3.0 (2.0 to 5.0)	2.0 (1.0 to 3.0)	3.0 (1.0 to 8.0)
Baseline: Radiologist (n=44, 34, 46)	1.0 (1.0 to 4.0)	1.0 (1.0 to 3.0)	1.0 (1.0 to 4.0)
Baseline: Home healthcare services (n=1, 1, 1)	1.0 (1.0 to 1.0)	1.0 (1.0 to 1.0)	24.0 (24.0 to 24.0)
Baseline: Other practitioner (n=13, 15, 21)	1.0 (1.0 to 6.0)	1.0 (1.0 to 2.0)	1.0 (1.0 to 12.0)
Week 32: Primary Care Physician (n=62, 61, 57)	1.0 (1.0 to 101.0)	1.0 (1.0 to 100.0)	1.0 (1.0 to 190.0)
Week 32: Neurologist (n=1, 4, 2)	1.0 (1.0 to 1.0)	1.0 (1.0 to 1.0)	51.0 (1.0 to 101.0)
Week 32: Rheumatologist (n=23, 34, 33)	1.0 (1.0 to 10.0)	1.0 (1.0 to 3.0)	1.0 (1.0 to 20.0)
Week 32: Pa or nurse Practitioner (n=9, 4, 3)	1.0 (1.0 to 111.0)	2.0 (1.0 to 3.0)	4.0 (1.0 to 101.0)
Week 32: Pain specialist (n=6, 7, 9)	1.0 (1.0 to 3.0)	1.0 (1.0 to 2.0)	1.0 (1.0 to 16.0)
Week 32: Orthopedist (n=34, 36, 35)	1.0 (1.0 to 111.0)	1.0 (1.0 to 6.0)	1.0 (1.0 to 2.0)
Week 32: Physical therapist (n=11, 12, 12)	8.0 (1.0 to 111.0)	2.0 (1.0 to 12.0)	5.5 (1.0 to 16.0)
Week 32: Chiropractor (n=0, 1, 1)	0 (0 to 0)	8.0 (8.0 to 8.0)	2.0 (2.0 to 2.0)
Week 32: Alternative medicine/therapy (n=5, 2, 6)	3.0 (1.0 to 10.0)	2.5 (1.0 to 4.0)	1.5 (1.0 to 10.0)
Week 32: Podiatrist (n=4, 4, 1)	1.0 (1.0 to 1.0)	1.5 (1.0 to 2.0)	1.0 (1.0 to 1.0)
Week 32: Nutritionist/dietitian (n=2, 1, 1)	1.0 (1.0 to 1.0)	1.0 (1.0 to 1.0)	2.0 (2.0 to 2.0)
Week 32: Radiologist (n=10, 10, 14)	1.0 (1.0 to 2.0)	1.0 (1.0 to 3.0)	1.0 (1.0 to 2.0)
Week 32: Home healthcare services (n=1, 1, 1)	10.0 (10.0 to 10.0)	1.0 (1.0 to 1.0)	10.0 (10.0 to 10.0)
Week 32: Other practitioner (n=13, 12, 14)	1.0 (1.0 to 8.0)	1.0 (1.0 to 8.0)	1.0 (1.0 to 16.0)
Week 48: Primary Care Physician (n=53, 63, 64)	1.0 (1.0 to 7.0)	1.0 (1.0 to 90.0)	2.0 (1.0 to 100.0)
Week 48: Neurologist (n=3, 5, 1)	1.0 (1.0 to 4.0)	1.0 (1.0 to 2.0)	2.0 (2.0 to 2.0)
Week 48: Rheumatologist (n=16, 34, 27)	1.0 (1.0 to 3.0)	1.0 (1.0 to 90.0)	1.0 (1.0 to 3.0)
Week 48: Pa or nurse Practitioner (n=4, 8, 4)	5.5 (2.0 to 55.0)	2.5 (1.0 to 90.0)	2.0 (1.0 to 4.0)
Week 48: Pain specialist (n=4, 3, 2)	1.0 (1.0 to 1.0)	3.0 (1.0 to 90.0)	1.0 (1.0 to 1.0)
Week 48: Orthopedist (n=31, 44, 55)	2.0 (1.0 to 6.0)	2.0 (1.0 to 90.0)	2.0 (1.0 to 8.0)
Week 48: Physical therapist (n=13, 19, 20)	6.0 (1.0 to 16.0)	6.0 (1.0 to 90.0)	10.0 (1.0 to 36.0)
Week 48: Chiropractor (n=2, 2, 1)	1.0 (1.0 to 1.0)	46.5 (3.0 to 90.0)	3.0 (3.0 to 3.0)
Week 48: Alternative medicine/therapy (n=0, 6, 3)	0 (0 to 0)	11.0 (3.0 to 90.0)	3.0 (2.0 to 5.0)
Week 48: Podiatrist (n=5, 3, 3)	1.0 (1.0 to 2.0)	1.0 (1.0 to 190.0)	3.0 (1.0 to 110.0)
Week 48: Nutritionist/dietitian (n=3, 1, 3)	1.0 (1.0 to 2.0)	130.0 (130.0 to 130.0)	1.0 (1.0 to 2.0)
Week 48: Radiologist (n=5, 8, 11)	1.0 (1.0 to 1.0)	1.5 (1.0 to 190.0)	1.0 (1.0 to 91.0)
Week 48: Home healthcare services (n=0, 3, 0)	0 (0 to 0)	5.0 (1.0 to 90.0)	0 (0 to 0)
Week 48: Other practitioner (n=6, 13, 9)	1.0 (1.0 to 3.0)	1.0 (1.0 to 90.0)	2.0 (1.0 to 4.0)

No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Visited the Emergency Room Due to Osteoarthritis

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End point title

Health Care Resource Utilization (HCRU): Number of Subjects who Visited the Emergency Room Due to Osteoarthritis

End point description

Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of subjects who visited the emergency room due to osteoarthritis. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
Baseline (n=281, 282, 284)	1	3	2
Week 32 (n=250, 260, 251)	2	2	0
Week 48 (n=218, 240, 231)	2	1	2

No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis

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End point title

Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis

End point description

Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of visits to the emergency room due to OA. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: visits
median (full range (min-max))
Baseline (n=1, 3, 2)	1.0 (1.0 to 1.0)	2.0 (1.0 to 2.0)	1.5 (1.0 to 2.0)
Week 32 (n=2, 2, 0)	1.5 (1.0 to 2.0)	1.0 (1.0 to 1.0)	0 (0 to 0)
Week 48 (n=2, 1, 2)	2.0 (1.0 to 3.0)	2.0 (2.0 to 2.0)	1.0 (1.0 to 1.0)

No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects Hospitalized Due to Osteoarthritis

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End point title

Health Care Resource Utilization (HCRU): Number of Subjects Hospitalized Due to Osteoarthritis

End point description

Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of subjects who were hospitalized due to OA. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
Baseline (n= 281, 282, 284)	1	2	1
Week 32 (n= 250, 260, 251)	1	1	1
Week 48 (218, 240, 231)	0	1	5

No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis

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End point title

Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis

End point description

Osteoarthritis HCRU assessed healthcare usage during last 3 months (for Baseline and Week 48) and past 8 weeks (for Week 32). Domain evaluated was number of nights stayed in the hospital due to OA. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: nights
median (full range (min-max))
Baseline (n=1, 2, 1)	1.0 (1.0 to 1.0)	11.0 (1.0 to 21.0)	1.0 (1.0 to 1.0)
Week 32 (n=1, 1, 1)	5.0 (5.0 to 5.0)	21.0 (21.0 to 21.0)	2.0 (2.0 to 2.0)
Week 48 (n=0, 1, 5)	0 (0 to 0)	1.0 (1.0 to 1.0)	1.0 (1.0 to 9.0)

No statistical analyses for this end point

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

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End point title

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

End point description

Osteoarthritis HCRU assessed healthcare usage during last 3 months (for baseline and week 48) and past 8 weeks (for week 32). Domain evaluated was number of subjects who used any aids/devices for doing things. Aids such as walking aid, wheelchair, device or utensil for dress/bathe/eat and any other aids/devices. Response for each aid/device usage was in terms of Never (Ne), Rarely (R), Sometimes (S), Often (O) and Always (A). The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint for specified categories.

End point type

Secondary

End point timeframe

Baseline, Weeks 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
Baseline:Walking aid use(n=281,282,284):Ne	250	240	242
Baseline: Wheelchair use(n=281,282,284):Ne	281	282	283
Baseline:Device to DressBatheEat(n=281,282,284):Ne	271	274	279
Baseline:Other aids/devices(n=281,282,284):Ne	275	265	270
Week 32: Walking aid use(n=250,260,251):Ne	225	232	214
Week 32: Wheelchair use(n=250,260,251):Ne	248	260	250
Week 32: Device to DressBatheEat(n=250,260,251):Ne	248	257	246
Week 32: Other aids/devices(n=250,260,251):Ne	246	252	245
Week 48: Walking aid use(n=218,240,231):Ne	200	211	191
Week 48: Wheelchair use(n=218,240,231):Ne	217	240	230
Week 48: Device to DressBatheEat(n=218,240,231):Ne	217	238	228
Week 48: Other aids/devices(n=218,240,231):Ne	215	234	225
Baseline:Walking aid use(n=281,282,284):R	4	8	5
Baseline: Wheelchair use(n=281,282,284):R	0	0	0
Baseline:Device to DressBatheEat(n=281,282,284):R	1	2	0
Baseline:Other aids/devices(n=281,282,284):R	2	2	5
Week 32: Walking aid use(n=250,260,251):R	4	1	6
Week 32: Wheelchair use(n=250,260,251):R	1	0	0
Week 32: Device to DressBatheEat(n=250,260,251):R	0	0	1
Week 32: Other aids/devices(n=250,260,251):R	0	0	1
Week 48: Walking aid use(n=218,240,231):R	1	2	3
Week 48: Wheelchair use(n=218,240,231):R	0	0	0
Week 48: Device to DressBatheEat(n=218,240,231):R	1	0	0
Week 48: Other aids/devices(n=218,240,231):R	1	0	1
Baseline:Walking aid use(n=281,282,284):S	11	13	15
Baseline: Wheelchair use(n=281,282,284):S	0	0	0
Baseline:Device to DressBatheEat(n=281,282,284):S	4	2	2
Baseline:Other aids/devices(n=281,282,284):S	0	8	4
Week 32: Walking aid use(n=250,260,251):S	8	8	10
Week 32: Wheelchair use(n=250,260,251):S	0	0	0
Week 32: Device to DressBatheEat(n=250,260,251):S	1	2	2
Week 32: Other aids/devices(n=250,260,251):S	2	4	3
Week 48: Walking aid use(n=218,240,231):S	6	12	13
Week 48: Wheelchair use(n=218,240,231):S	0	0	0
Week 48: Device to DressBatheEat(n=218,240,231):S	0	0	2
Week 48: Other aids/devices(n=218,240,231):S	2	2	1
Baseline:Walking aid use(n=281,282,284):O	7	12	7
Baseline: Wheelchair use(n=281,282,284):O	0	0	1
Baseline:Device to DressBatheEat(n=281,282,284):O	2	0	3
Baseline:Other aids/devices(n=281,282,284):O	3	5	3
Week 32: Walking aid use(n=250,260,251):O	4	7	12
Week 32: Wheelchair use(n=250,260,251):O	0	0	1
Week 32: Device to DressBatheEat(n=250,260,251):O	0	0	1
Week 32: Other aids/devices(n=250,260,251):O	1	4	1
Week 48: Walking aid use(n=218,240,231):O	4	8	10
Week 48: Wheelchair use(n=218,240,231):O	0	0	1
Week 48: Device to DressBatheEat(n=218,240,231):O	0	0	0
Week 48: Other aids/devices(n=218,240,231):O	0	3	3
Baseline:Walking aid use(n=281,282,284):A	9	9	15
Baseline: Wheelchair use(n=281,282,284):A	0	0	0
Baseline:Device to DressBatheEat(n=281,282,284):A	3	4	0
Baseline:Other aids/devices(n=281,282,284):A	1	2	2
Week 32: Walking aid use(n=250,260,251):A	9	12	9
Week 32: Wheelchair use(n=250,260,251):A	1	0	0
Week 32: Device to DressBatheEat(n=250,260,251):A	1	1	1
Week 32: Other aids/devices(n=250,260,251):A	1	0	1
Week 48: Walking aid use(n=218,240,231):A	7	7	14
Week 48: Wheelchair use(n=218,240,231)A	1	0	0
Week 48: Device to DressBatheEat(n=218,240,231):A	0	2	1
Week 48: Other aids/devices(n=218,240,231):A	0	1	1

No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Quit Job Due to Osteoarthritis

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End point title

Health Care Resource Utilization (HCRU): Number of Subjects who Quit Job Due to Osteoarthritis

End point description

Osteoarthritis HCRU assessed healthcare usage (during 3 months prior to baseline) at baseline, Week 32 and Week 48. Domain evaluated was number of subjects who quit job due to OA. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
Baseline (n=281, 282, 284)	13	12	9
Week 32 (n=250, 260, 251)	7	9	4
Week 48 (218, 240, 231)	7	7	4

No statistical analyses for this end point

Secondary: Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis

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End point title

Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis

End point description

Osteoarthritis HCRU assessed healthcare usage (during 3 months prior to baseline) at baseline, Week 32 and Week 48. Domain evaluated was duration since quitting job due to OA. ITT population: all randomized subjects who received at least one dose of SC study medication (either Tanezumab or placebo). One additional subject apart from the ones who had responded for quitting job responded to duration since quitting job. ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: years
median (full range (min-max))
Baseline (n=13, 12, 9)	2.0 (0.1 to 20.9)	1.0 (0.2 to 7.0)	5.3 (0.1 to 30.0)
Week 32 (n=7, 10, 4)	0.5 (0.3 to 2.9)	2.4 (0.2 to 17.8)	1.1 (0.1 to 10.2)
Week 48 (n=7, 7, 4)	0.8 (0.3 to 2.8)	2.5 (0.6 to 10.0)	0.7 (0.1 to 1.5)

No statistical analyses for this end point

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

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End point title

Number of Subjects Who Withdrew Due to Lack of Efficacy

End point description

Number of subjects who withdrew from treatment due to lack of efficacy have been reported here. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects	18	2	3

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Logistic regression model included baseline diary average pain, baseline WOMAC pain score, classification variables index joint, highest Kellgren-Lawrence grade and treatment. Odds ratio and 95% CI estimated from logistic regression model.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0027

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.02

upper limit

0.46

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0033

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

0.54

Secondary: Time to Discontinuation Due to Lack of Efficacy

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End point title

Time to Discontinuation Due to Lack of Efficacy

End point description

Time to discontinuation due to lack of efficacy was defined as the time interval from the date of first study drug administration up to the date of discontinuation of subject from treatment due to lack of efficacy. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘number of subjects analysed’ signifies subjects who discontinued from the study due to lack of efficacy. Due to the Kaplan-Meier estimate not reaching the level for discontinuation due to lack of efficacy, median and upper limit could not be calculated and has been denoted by 99999.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	18	2	3
Units: days
median (full range (min-max))	99999 (10 to 99999)	99999 (27 to 99999)	99999 (12 to 99999)

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Missing data for the selected percentile(s) was due to the Kaplan-Meier estimate not reaching the level for discontinuation due to lack of efficacy.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007 ^[13]

Method

Logrank

Confidence interval

Notes
[13] - P-value based on the log-rank test.

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Missing data for the selected percentile(s) was due to the Kaplan-Meier estimate not reaching the level for discontinuation due to lack of efficacy.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002 ^[14]

Method

Logrank

Confidence interval

Notes
[14] - P-value based on the log-rank test.

Secondary: Number of Subjects Who Took Rescue Medication during Weeks 2, 4, 8, 12, 16 and 24

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End point title

Number of Subjects Who Took Rescue Medication during Weeks 2, 4, 8, 12, 16 and 24

End point description

In case of inadequate pain relief, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication between day 1 and week 24. Number of subjects with any use of rescue medication during the particular study week were summarized. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
Week 2	205	150	169
Week 4	181	134	150
Week 8	166	135	146
Week 12	151	122	122
Week 16	154	130	122
Week 24	126	127	115

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

0.59

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

0.78

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

0.7

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 4: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0067

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

0.88

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0087

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

0.89

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 8: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0787

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

1.04

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0129

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

0.91

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0399

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

0.98

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 12: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0124

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

0.91

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9449

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.42

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 16: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

0.87

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 24: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade and treatment.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3238

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.18

Secondary: Number of Subjects Who Took Rescue Medication during Week 32

Top of page

End point title

Number of Subjects Who Took Rescue Medication during Week 32

End point description

In case of inadequate pain relief, after Week 24, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of subjects with any use of rescue medication during the 4 weeks up to and including the particular study week were summarized. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘number of subjects analysed’ signifies subjects who were evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	231	251	249
Units: subjects	130	158	149

No statistical analyses for this end point

Secondary: Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16 and 24

Top of page

End point title

Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16 and 24

End point description

In case of inadequate pain relief during the treatment period, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week a could be taken as rescue medication. Number of days the subjects used the rescue medication during the particular study weeks were summarized. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: days
least squares mean (standard error)
Week 2	3.17 ± 0.27	2.12 ± 0.19	2.39 ± 0.21
Week 4	2.82 ± 0.28	1.81 ± 0.18	2.07 ± 0.21
Week 8	2.54 ± 0.26	1.83 ± 0.19	1.92 ± 0.20
Week 12	2.29 ± 0.27	1.70 ± 0.20	1.72 ± 0.20
Week 16	2.11 ± 0.24	1.64 ± 0.19	1.70 ± 0.19
Week 24	1.74 ± 0.22	1.49 ± 0.18	1.43 ± 0.18

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 2: Least square (LS) Mean was ratio of treatments. Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, and treatment group.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

0.82

Variability estimate

Standard error of the mean

Dispersion value

0.07

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Week 2: LS Mean was ratio of treatments. Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, and treatment group.

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0067

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

0.92

Variability estimate

Standard error of the mean

Dispersion value

0.08

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 4: LS Mean was ratio of treatments. Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, and treatment group.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

0.82

Variability estimate

Standard error of the mean

Dispersion value

0.08

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0112

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

0.93

Variability estimate

Standard error of the mean

Dispersion value

0.09

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 8: LS Mean was ratio of treatments. Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, and treatment group.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0093

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

0.92

Variability estimate

Standard error of the mean

Dispersion value

0.09

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0237

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

0.96

Variability estimate

Standard error of the mean

Dispersion value

0.09

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 12: LS Mean was ratio of treatments. Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, and treatment group.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0374

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

0.98

Variability estimate

Standard error of the mean

Dispersion value

0.11

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0468

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.11

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 16: LS Mean was ratio of treatments. Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, and treatment group.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0751

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

1.03

Variability estimate

Standard error of the mean

Dispersion value

0.11

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1305

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.06

Variability estimate

Standard error of the mean

Dispersion value

0.11

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Week 24: LS Mean was ratio of treatments. Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, and treatment group.

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3057

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.16

Variability estimate

Standard error of the mean

Dispersion value

0.13

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2056

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

1.11

Variability estimate

Standard error of the mean

Dispersion value

0.13

Secondary: Number of Days of Rescue Medication Used at Week 32

Top of page

End point title

Number of Days of Rescue Medication Used at Week 32

End point description

In case of inadequate pain relief, after Week 24, acetaminophen/paracetamol up to 4000 mg per day up to 7 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of days per week the subjects used the rescue medication during the 4 weeks up to and including the particular study week were summarized. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, ‘number of subjects analysed’ signifies subjects who took rescue medication.

End point type

Secondary

End point timeframe

Week 32

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	231	251	249
Units: days
arithmetic mean (standard deviation)	1.8 ± 2.24	2.2 ± 2.34	2.0 ± 2.28

No statistical analyses for this end point

Secondary: Amount of Rescue Medication Used at Weeks 2, 4, 8, 12, 16 and 24

Top of page

End point title

Amount of Rescue Medication Used at Weeks 2, 4, 8, 12, 16 and 24

End point description

In case of inadequate pain relief, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication. The total dosage of acetaminophen in milligrams used during the specified week were summarized. The intent to treat population included all randomized subjects who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

End point type

Secondary

End point timeframe

Weeks 2, 4, 8, 12, 16 and 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: milligrams
least squares mean (standard error)
Week 2	3690.6 ± 714.30	2283.4 ± 444.56	2703.4 ± 516.83
Week 4	3139.0 ± 707.35	1868.9 ± 396.26	2366.6 ± 529.63
Week 8	2940.9 ± 678.61	1902.4 ± 425.30	2269.4 ± 523.10
Week 12	2893.1 ± 749.38	1950.1 ± 495.07	1992.3 ± 509.28
Week 16	2627.1 ± 658.47	1864.2 ± 458.32	1897.6 ± 466.14
Week 24	2273.8 ± 625.84	1868.1 ± 482.13	1828.8 ± 491.51

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0441

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

0.99

Variability estimate

Standard error of the mean

Dispersion value

0.15

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1895

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

1.17

Variability estimate

Standard error of the mean

Dispersion value

0.17

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0567

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

1.01

Variability estimate

Standard error of the mean

Dispersion value

0.16

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.296

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

1.28

Variability estimate

Standard error of the mean

Dispersion value

0.2

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1215

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

1.12

Variability estimate

Standard error of the mean

Dispersion value

0.18

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3569

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

1.34

Variability estimate

Standard error of the mean

Dispersion value

0.22

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2096

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

1.25

Variability estimate

Standard error of the mean

Dispersion value

0.21

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2387

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

1.28

Variability estimate

Standard error of the mean

Dispersion value

0.22

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2627

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

1.29

Variability estimate

Standard error of the mean

Dispersion value

0.22

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2863

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.31

Variability estimate

Standard error of the mean

Dispersion value

0.22

Placebo Versus Tanezumab 2.5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 2.5 mg

Number of subjects included in analysis

565

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.556

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

1.58

Variability estimate

Standard error of the mean

Dispersion value

0.27

Placebo Versus Tanezumab 5 mg

Statistical analysis description

Comparison groups

Placebo v Tanezumab 5 mg

Number of subjects included in analysis

566

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5076

Method

Negative binomial model

Parameter type

LS Mean Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.53

Variability estimate

Standard error of the mean

Dispersion value

0.26

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

Top of page

End point title

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

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to week 48 that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously.

End point type

Secondary

End point timeframe

Baseline up to Week 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
AEs	178	184	198
SAEs	11	24	27

No statistical analyses for this end point

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

Top of page

End point title

Number of Subjects With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) up to End of Study

End point description

Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to week 48 that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously.

End point type

Secondary

End point timeframe

Baseline up to Week 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
AEs	46	52	59
SAEs	1	0	3

No statistical analyses for this end point

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

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End point title

Number of Subjects With Laboratory Test Abnormalities With Regard to Normal Baseline

End point description

Primary Abnormality criteria:HGB,hematocrit,RBC count<0.8*lower limit of normal(LLN);Ery.MCV/hemoglobin/ HGB concentration,RBCs distribution width<0.9*LLN, >1.1*upper limit of normal(ULN);platelets <0.5*LLN,>1.75*ULN;WBC count<0.6*LLN, >1.5*ULN;Lymphocytes,Leukocytes,Neutrophils <0.8*LLN, >1.2*ULN;Basophils,Eosinophils,Monocytes>1.2*ULN;Prothrombin time/Intl.normalized ratio>1.1*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase,alanine aminotransferase,gamma GT,LDH,alkaline phosphatase >3.0*ULN;total protein; albumin<0.8*LLN,>1.2*ULN; blood urea nitrogen,creatinine,Cholesterol,triglycerides >1.3*ULN;Urate>1.2*ULN;sodium<0.95*LLN,>1.05*ULN;potassium,chloride,calcium,magnesium,bicarbonate <0.9*LLN, >1.1*ULN;phosphate<0.8*LLN, >1.2*ULN;glucose<0.6*LLN,>1.5*ULN;HGB A1C >1.3*ULN;creatine kinase>2.0*ULN,specific gravity<1.003, >1.030;pH<4.5, >8;Urine Glucose,protein,HGB,bilirubin >=1;Ketones>=1;Urine erythrocytes,Leukocytes>=20. Safety population, N=evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	265	271	274
Units: subjects	32	34	34

No statistical analyses for this end point

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

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End point title

Number of Subjects With Laboratory Test Abnormalities With Regard to Abnormal Baseline

End point description

Primary Abnormality criteria: hemoglobin; hematocrit; RBC count < 0.8*LLN; Ery. mean corpuscular volume/ hemoglobin/ HGB concentration, erythrocytes distribution width <0.9*LLN, >1.1*ULN; platelets <0.5*LLN,>1.75*upper limit of normal (ULN); white blood cell count<0.6*LLN, >1.5*ULN; Lymphocytes, Leukocytes, Neutrophils <0.8*LLN, >1.2*ULN; Basophils, Eosinophils, Monocytes >1.2*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase, alanine aminotransferase, gamma GT,LDH, alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen, creatinine, Cholesterol, triglycerides >1.3*ULN; Urate >1.2*ULN; sodium <0.95*LLN,>1.05*ULN; potassium, chloride, calcium, magnesium, bicarbonate <0.9*LLN, >1.1*ULN; phosphate <0.8*LLN, >1.2*ULN; glucose <0.6*LLN, >1.5*ULN; Hemoglobin A1C >1.3*ULN; creatine kinase >2.0*ULN; Nitrite >=1. Safety population. N=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	205	215	207
Units: subjects	19	26	22

No statistical analyses for this end point

Secondary: Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48

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End point title

Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48

End point description

Measurement of BP included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP). The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘n’ = subjects evaluable for this endpoint for specified categories.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: millimeters of mercury (mmHg)
arithmetic mean (standard deviation)
SBP: Baseline (n= 282, 283, 284)	132.0 ± 13.54	132.7 ± 12.59	132.0 ± 12.12
SBP:Change at Week 2 (n= 276, 278, 278)	-1.0 ± 10.26	-2.0 ± 11.24	-2.4 ± 11.24
SBP:Change at Week 4 (n= 272, 280, 278)	-0.3 ± 11.09	-2.0 ± 10.94	-2.4 ± 11.52
SBP:Change at Week 8 (n= 265, 275, 275)	-0.8 ± 10.89	-2.1 ± 10.63	-2.5 ± 12.07
SBP:Change at Week 12 (n= 255, 274, 271)	-1.2 ± 11.38	-1.8 ± 11.53	-2.8 ± 11.64
SBP:Change at Week 16 (n= 242, 265, 265)	-0.4 ± 12.18	-1.6 ± 12.92	-2.3 ± 11.63
SBP:Change at Week 24 (n= 236, 255, 254)	-1.5 ± 11.47	-2.0 ± 12.55	-2.5 ± 12.11
SBP:Change at Week 32 (n= 228, 251, 139)	-2.1 ± 12.61	-1.8 ± 12.40	-1.0 ± 12.55
SBP:Change at Week 48 (n= 220, 242, 229)	-0.7 ± 10.38	-1.7 ± 11.60	-1.8 ± 11.34
DBP: Baseline (n= 282, 283, 284)	79.7 ± 8.28	79.3 ± 8.45	79.5 ± 8.10
DBP:Change at Week 2 (n= 276, 278, 278)	-0.4 ± 6.81	-1.7 ± 7.18	-1.7 ± 7.33
DBP:Change at Week 4 (272, 280, 278)	-0.6 ± 7.06	-1.7 ± 7.35	-1.8 ± 7.85
DBP:Change at Week 8 (265, 275, 275)	-0.1 ± 7.59	-1.0 ± 7.11	-1.7 ± 7.65
DBP:Change at Week 12 (255, 274, 271)	-1.0 ± 7.44	-1.3 ± 7.79	-2.8 ± 7.94
DBP:Change at Week 16 (242, 265, 265)	-0.7 ± 7.85	-0.6 ± 8.26	-1.8 ± 7.90
DBP:Change at Week 24 (236, 255, 254)	-0.1 ± 7.81	-0.2 ± 8.42	-2.0 ± 7.90
DBP:Change at Week 32 (228, 251, 239)	-1.2 ± 8.52	-0.7 ± 8.06	-1.5 ± 8.64
DBP:Change at Week 48 (282, 283, 284)	-0.6 ± 7.22	-0.7 ± 8.32	-0.9 ± 8.17

No statistical analyses for this end point

Secondary: Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48

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End point title

Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48

End point description

Heart rate was measured at sitting position. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘n’ = subjects evaluable for this endpoint for specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12,16, 24, 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: beats per minute
arithmetic mean (standard deviation)
Baseline (n= 282, 283, 283)	71.1 ± 8.45	70.4 ± 8.62	70.8 ± 8.33
Change at Week 2 (275, 277, 277)	0.2 ± 7.26	1.2 ± 7.25	0.2 ± 8.45
Change at Week 4 (n= 272, 280, 277)	0.8 ± 7.92	0.9 ± 7.91	-0.1 ± 7.99
Change at Week 8 (265, 275, 274)	0.5 ± 7.61	-0.3 ± 8.08	-0.9 ± 7.54
Change at Week 12 (n= 255, 274, 270)	0.9 ± 8.14	1.6 ± 8.28	0.5 ± 8.39
Change at Week 16 (n= 242, 265, 264)	-0.3 ± 8.13	-0.4 ± 8.01	-0.0 ± 8.12
Change at Week 24 (n= 236, 255, 253)	-0.5 ± 8.56	0.5 ± 8.77	0.4 ± 8.86
Change at Week 32 (n= 228, 251, 238)	1.1 ± 8.51	0.8 ± 8.19	0.6 ± 9.40
Change at Week 48 (220, 242, 228)	-0.2 ± 8.13	1.4 ± 9.87	0.6 ± 10.01

No statistical analyses for this end point

Secondary: Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48

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End point title

Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48

End point description

A 12–lead ECG was recorded after subjects had rested for at least 5 minutes in the supine position in a quiet environment. All standard intervals (PR, QRS, QT, QTcF, QTcB, QTcF, RR intervals) were collected. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘n’ = subjects evaluable for this endpoint for specified categories.

End point type

Secondary

End point timeframe

Baseline, Weeks 24 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: millisecond
arithmetic mean (standard deviation)
RR Interval: Baseline (n=282, 283, 284)	923.9 ± 124.86	923.6 ± 139.69	928.3 ± 126.14
RR Interval:Change at Week 24 (n=236, 254, 252)	-3.2 ± 108.30	-14.6 ± 119.62	-16.1 ± 124.65
RR Interval:Change at Week 48 (n=216, 238, 224)	-19.0 ± 118.49	-16.0 ± 112.48	-26.7 ± 125.81
PR Interval: Baseline (n=276, 278, 277)	168.7 ± 23.95	165.6 ± 21.92	168.0 ± 24.54
PR Interval:Change at Week 24 (n= 229, 248, 240)	0.1 ± 14.07	0.5 ± 13.38	2.0 ± 15.43
PR Interval:Change at Week 48 (n= 209, 231, 213)	1.3 ± 13.64	-1.1 ± 14.38	-0.4 ± 14.23
QRS Interval: Baseline (n= 282, 283, 284)	95.7 ± 12.69	95.6 ± 14.05	95.8 ± 14.48
QRS Interval:Change at Week 24 (n= 236, 254, 252)	-0.2 ± 7.22	0.2 ± 7.57	0.0 ± 7.34
QRS Interval:Change at Week 48 (n= 216, 238, 224)	-0.2 ± 8.04	0.2 ± 8.33	0.8 ± 8.73
QT Interval: Baseline (n=281, 282, 283)	402.0 ± 28.45	403.1 ± 29.92	405.6 ± 26.84
QT Interval:Change at Week 24 (n= 234, 252, 251)	-2.2 ± 22.65	-3.1 ± 21.78	-3.8 ± 25.84
QT Interval:Change at Week 48 (n= 215, 237, 222)	-2.5 ± 23.27	-1.6 ± 24.40	-4.9 ± 24.06
QTCB Interval: Baseline (n= 281, 282, 283)	419.8 ± 22.32	421.3 ± 20.78	422.5 ± 20.57
QTCB Interval:Change at Week 24 (n= 234, 252, 251)	-1.5 ± 17.56	0.2 ± 18.47	0.0 ± 16.26
QTCB Interval:Change at Week 48 (n= 215, 237, 222)	1.5 ± 16.45	1.7 ± 16.70	1.8 ± 16.80
QTCF Interval: Baseline (n= 281, 282, 283 )	413.6 ± 20.70	414.9 ± 19.23	416.6 ± 18.61
QTCF Interval:Change at Week 24 (n= 234, 252, 251)	-1.7 ± 15.72	-1.0 ± 14.94	-1.3 ± 15.05
QTCF Interval:Change at Week 48 (n= 215, 237, 222)	0.2 ± 14.50	0.5 ± 15.58	-0.5 ± 13.96

No statistical analyses for this end point

Secondary: Change From Baseline in Heart Rate (as assessed by ECG) at Weeks 24 and 48

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End point title

Change From Baseline in Heart Rate (as assessed by ECG) at Weeks 24 and 48

End point description

Heart rate was measured at sitting position. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 24 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: beats per minute
arithmetic mean (standard deviation)
Baseline (n= 282, 283, 284 )	66.2 ± 9.28	66.5 ± 10.69	65.9 ± 9.22
change at Week 24 (n= 236, 254, 252)	0.3 ± 8.05	0.9 ± 9.15	1.4 ± 10.19
Change at Week 48 (216, 238, 224)	1.4 ± 8.59	1.1 ± 8.98	2.3 ± 10.44

No statistical analyses for this end point

Secondary: Percentage of Subjects With Adjudicated Joint Safety Outcomes

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End point title

Percentage of Subjects With Adjudicated Joint Safety Outcomes

End point description

Incidence of subjects with any of the joint safety adjudication outcomes of primary osteonecrosis, rapidly progressive OA (type 1 and type 2), subchondral insufficiency fracture (or SPONK), or pathological fracture. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘number of subjects analysed’ signifies subjects analysed by adjudication committee.

End point type

Secondary

End point timeframe

Baseline up to Week 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	19	27	33
Units: percentage of subjects
number (confidence interval 95%)
Composite Joint Safety Endpoint	0 (0.0 to 1.3)	1.8 (0.6 to 4.1)	3.2 (1.5 to 5.9)
Rapidly Progressive OA	0 (0.0 to 1.3)	1.4 (0.4 to 3.6)	2.8 (1.2 to 5.5)
Rapidly Progressive OA type 1	0 (0.0 to 1.3)	1.1 (0.2 to 3.1)	1.8 (0.6 to 4.1)
Rapidly Progressive OA type 2	0 (0.0 to 1.3)	0.4 (0.0 to 2.0)	1.1 (0.2 to 3.1)
Primary Osteonecrosis	0 (0.0 to 1.3)	0 (0.0 to 1.3)	0.4 (0.0 to 1.9)
Pathological Fracture	0 (0.0 to 1.3)	0 (0.0 to 1.3)	0 (0.0 to 1.3)
Subchondral Insufficiency Fracture	0 (0.0 to 1.3)	0.4 (0.0 to 2.0)	0 (0.0 to 1.3)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Total Joint Replacements

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End point title

Percentage of Subjects With Total Joint Replacements

End point description

Percentage of subjects who underwent at least one total knee, hip or shoulder joint replacement surgery. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously.

End point type

Secondary

End point timeframe

Baseline up to Week 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: percentage of subjects
number (confidence interval 95%)	6.7 (4.1 to 10.3)	7.8 (4.9 to 11.5)	7.0 (4.4 to 10.7)

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 BP <=150 mmHg (mean supine): Reduction in systolic BP>=20 mmHg or reduction in diastolic BP>=10 mmHg at the 1 and/or 3 minute standing BP measurements. For systolic BP >150 mmHg (mean supine): Reduction in systolic BP>=30 mmHg or reduction in diastolic BP>=15 mmHg at the 1 and/or 3 minute standing BP measurements. If the 1 minute or 3 minute standing BP in a sequence met the orthostatic hypotension criteria, then that sequence was considered positive. If 2 of 2 or 2 of 3 sequences were positive, then orthostatic hypotension was considered confirmed. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘number of subjects analysed’ signifies subjects analysed for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	221	242	228
Units: subjects
Baseline	0	1	0
Week 2	0	0	0
Week 4	0	0	1
Week 8	0	0	1
Week 12	0	0	0
Week 16	0	0	1
Week 24	0	0	0
Week 32	0	0	0
Week 48	0	1	1

No statistical analyses for this end point

Secondary: Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Week 24

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End point title

Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Week 24

End point description

The SAS is a 12 item (11 for females) questionnaire, from which the total number of symptoms (NoS) (0-12 for males and 0-11 for females) is calculated. Each positive symptom is rated from 1 (not at all) to 5 (a lot). The total symptom impact score (SIS) was the sum of all symptom rating scores, with 0 assigned where the subject did not have the particular symptom. The range for the total impact score is 0-60 for males and 0-55 for females, higher scores indicating higher impact. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 24

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
NoS reported: Baseline (n=280,282,283)	0.55 ± 0.85	0.53 ± 0.85	0.55 ± 0.83
NoS reported: Change at Week 24 (n=232,255,254)	0.03 ± 1.07	0.15 ± 1.18	0.18 ± 1.22
Total SIS: Baseline (n=280,282,283)	1.14 ± 1.94	1.11 ± 1.79	1.20 ± 1.99
Total SIS: Change at Week 24 (n=232,255,254)	0.32 ± 2.92	0.53 ± 3.23	0.56 ± 3.11

No statistical analyses for this end point

Secondary: Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48

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End point title

Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48

End point description

NIS is a standardized instrument used to evaluate subject for signs of peripheral neuropathy. NIS is the sum of scores of 37 items, from both the left and right side, where 24 items scored from 0 (normal) to 4 (paralysis), higher score indicated higher abnormality/impairment and 13 items scored from 0 (normal), 1 (decreased) and 2 (absent), higher score indicated higher impairment. NIS possible overall score ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased impairment. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘n’ = subjects evaluable for this endpoint at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 4, 8, 12, 16, 24, 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 282, 283, 284)	1.35 ± 2.85	1.35 ± 3.72	1.48 ± 3.11
Change at Week 2 (n=280, 280, 276)	0.03 ± 0.92	-0.09 ± 0.68	-0.21 ± 1.14
Change at Week 4 (n=282, 282, 281)	0.01 ± 1.16	0.00 ± 1.31	-0.32 ± 1.24
Change at Week 8 (n=282, 282, 283)	-0.11 ± 1.42	-0.13 ± 1.20	-0.41 ± 1.56
Change at Week 12 (n=282, 282, 283)	-0.12 ± 1.38	-0.03 ± 1.50	-0.39 ± 1.59
Change at Week 16 (n=282, 282, 283)	-0.17 ± 1.59	-0.03 ± 1.72	-0.46 ± 1.53
Change at Week 24 (n=282, 282, 283)	-0.20 ± 1.51	-0.01 ± 1.85	-0.47 ± 1.58
Change at Week 32 (n=282, 282, 283)	-0.23 ± 1.69	0.00 ± 1.75	-0.41 ± 1.57
Change at Week 48 (n=282, 282, 283)	-0.22 ± 1.67	0.01 ± 1.91	-0.43 ± 1.57

No statistical analyses for this end point

Secondary: Number of Subjects With Anti Tanezumab Antibodies

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End point title

Number of Subjects With Anti Tanezumab Antibodies

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). Subjects listed as having anti-tanezumab antibodies had ADA titer level >=3.32. Less than 3.32 was considered below the limit of quantitation. The safety population was defined as all subjects treated with tanezumab or placebo subcutaneously. Here, ‘n’=subjects evaluable for this end point at specified time points.

End point type

Secondary

End point timeframe

Baseline, Weeks 8,16, 24, 32 and 48

End point values	Placebo	Tanezumab 2.5 mg	Tanezumab 5 mg
Number of subjects analysed	282	283	284
Units: subjects
Baseline (n= 281, 281, 281)	24	26	36
Week 8 (n= 261, 275, 275)	24	27	41
Week 16 (n= 242, 263, 265)	25	34	48
Week 24 (n= 233, 253, 251)	19	39	49
Week 32 (n= 224, 247, 236)	19	38	42
Week 48 (n= 216, 242, 227)	18	32	31

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to Week 24

Adverse event reporting additional description

Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized 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. One death was accounted as lost to follow-up in subject disposition.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Placebo

Reporting group description

Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Reporting group title

Tanezumab 5 mg

Reporting group description

Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Reporting group title

Tanezumab 2.5 mg

Reporting group description

Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.

Serious adverse events	Placebo	Tanezumab 5 mg	Tanezumab 2.5 mg
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 282 (1.06%)	9 / 284 (3.17%)	8 / 283 (2.83%)
number of deaths (all causes)	0	2	1
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Nerve injury
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nerve root injury lumbar
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Lymphatic fistula
subjects affected / exposed	1 / 282 (0.35%)	0 / 284 (0.00%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	1 / 282 (0.35%)	0 / 284 (0.00%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ocular vascular disorder
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatitis
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 282 (0.35%)	2 / 284 (0.70%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 282 (0.00%)	0 / 284 (0.00%)	1 / 283 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 282 (0.00%)	1 / 284 (0.35%)	0 / 283 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Tanezumab 5 mg	Tanezumab 2.5 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	77 / 282 (27.30%)	60 / 284 (21.13%)	73 / 283 (25.80%)
Nervous system disorders
Headache
subjects affected / exposed	18 / 282 (6.38%)	14 / 284 (4.93%)	15 / 283 (5.30%)
occurrences all number	34	16	18
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	34 / 282 (12.06%)	22 / 284 (7.75%)	27 / 283 (9.54%)
occurrences all number	45	38	35
Back pain
subjects affected / exposed	15 / 282 (5.32%)	17 / 284 (5.99%)	16 / 283 (5.65%)
occurrences all number	16	17	19
Infections and infestations
Nasopharyngitis
subjects affected / exposed	25 / 282 (8.87%)	21 / 284 (7.39%)	31 / 283 (10.95%)
occurrences all number	28	26	32

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

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 in Subjects with Osteoarthritis of the Hip Or Knee

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24

Primary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24

Primary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24

Primary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24

Primary: Change from Baseline in the Patient’s Global Assessment (PGA) of Osteoarthritis at Week 24

Primary: Change from Baseline in the Patient’s Global Assessment (PGA) of Osteoarthritis at Week 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 32

Secondary: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 32

Secondary: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 32

Secondary: Percentage of Subjects Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index

Secondary: Percentage of Subjects Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24

Secondary: Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response

Secondary: Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response

Secondary: Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response

Secondary: Percentage of Subjects Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24

Secondary: Percentage of Subjects With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24

Secondary: Percentage of Subjects Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis

Secondary: Percentage of Subjects Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis

Secondary: Change From Baseline for Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24

Secondary: Change From Baseline for Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24

Secondary: Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32

Secondary: Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Weeks 2, 4, 8, 12, 16 and 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Weeks 2, 4, 8, 12, 16 and 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Weeks 2, 4, 8, 12, 16 and 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Weeks 2, 4, 8, 12, 16 and 24

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Week 32

Secondary: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Week 32

Secondary: Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline

Secondary: Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline

Secondary: Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24

Secondary: Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24

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

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

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

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

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Reported Treatment Impact Assessment-Overall, How Satisfied Are You With The Drug That You Received in This Study?

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Reported Treatment Impact Assessment-Overall, How Satisfied Are You With The Drug That You Received in This Study?

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Osteoarthritis Pain Before Enrolling?

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Osteoarthritis Pain Before Enrolling?

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment?

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment?

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Osteoarthritis Pain?

Secondary: Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 24: Subject Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Osteoarthritis Pain?

Secondary: Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis

Secondary: Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Visited the Emergency Room Due to Osteoarthritis

Secondary: Health Care Resource Utilization (HCRU): Number of Subjects who Visited the Emergency Room Due to Osteoarthritis

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 in Subjects with Osteoarthritis of the Hip Or Knee