Trial Outcomes & Findings for Study of the Analgesic Efficacy and Safety of Subcutaneous Tanezumab in Subjects With Osteoarthritis of the Hip or Knee. (NCT NCT02709486)

Results Overview

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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. 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

849 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2019-06-26

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Overall Study STARTED	282	283	284
Overall Study COMPLETED	238	249	239
Overall Study NOT COMPLETED	44	34	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Overall Study Adverse Event	2	5	3
Overall Study Death	0	0	2
Overall Study Insufficient clinical response	7	3	3
Overall Study Lost to Follow-up	3	2	2
Overall Study Other	0	2	3
Overall Study Withdrawal by Subject	32	22	32

Baseline Characteristics

Study of the Analgesic Efficacy and Safety of Subcutaneous Tanezumab in Subjects With Osteoarthritis of the Hip or Knee.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Total n=849 Participants Total of all reporting groups
Age, Continuous	64.24 years STANDARD_DEVIATION 9.58 • n=5 Participants	65.17 years STANDARD_DEVIATION 8.39 • n=7 Participants	65.23 years STANDARD_DEVIATION 10.16 • n=5 Participants	64.88 years STANDARD_DEVIATION 9.41 • n=4 Participants
Sex: Female, Male Female	196 Participants n=5 Participants	198 Participants n=7 Participants	193 Participants n=5 Participants	587 Participants n=4 Participants
Sex: Female, Male Male	86 Participants n=5 Participants	85 Participants n=7 Participants	91 Participants n=5 Participants	262 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=5 Participants	19 Participants n=7 Participants	10 Participants n=5 Participants	48 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	263 Participants n=5 Participants	264 Participants n=7 Participants	274 Participants n=5 Participants	801 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	247 Participants n=5 Participants	245 Participants n=7 Participants	248 Participants n=5 Participants	740 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	34 Participants n=5 Participants	38 Participants n=7 Participants	34 Participants n=5 Participants	106 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The intent to treat (ITT) population included all randomized participants who received at least one dose of subcutaneous (SC) study medication (either tanezumab or placebo).

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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. 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24	-2.24 units on a scale Standard Error 0.17	-2.70 units on a scale Standard Error 0.17	-2.85 units on a scale Standard Error 0.17

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant'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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24	-2.11 units on a scale Standard Error 0.17	-2.70 units on a scale Standard Error 0.17	-2.82 units on a scale Standard Error 0.17

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: The intent to treat population was defined as all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

PGA of OA was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in the Patient's Global Assessment (PGA) of Osteoarthritis at Week 24	-0.72 units on a scale Standard Error 0.06	-0.82 units on a scale Standard Error 0.06	-0.90 units on a scale Standard Error 0.06

SECONDARY outcome

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

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 2	-1.35 units on a scale Standard Error 0.14	-2.02 units on a scale Standard Error 0.14	-1.69 units on a scale Standard Error 0.14
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 4	-1.78 units on a scale Standard Error 0.15	-2.57 units on a scale Standard Error 0.15	-2.56 units on a scale Standard Error 0.15
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 8	-1.84 units on a scale Standard Error 0.15	-2.47 units on a scale Standard Error 0.15	-2.61 units on a scale Standard Error 0.15
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 12	-2.19 units on a scale Standard Error 0.17	-2.91 units on a scale Standard Error 0.16	-2.96 units on a scale Standard Error 0.16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 16	-2.10 units on a scale Standard Error 0.17	-2.69 units on a scale Standard Error 0.17	-2.69 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time point.

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 32 Baseline	6.59 units on a scale Standard Deviation 0.94	6.70 units on a scale Standard Deviation 0.94	6.60 units on a scale Standard Deviation 0.89
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 32 Change at Week 32	-2.70 units on a scale Standard Deviation 2.06	-2.29 units on a scale Standard Deviation 1.95	-2.26 units on a scale Standard Deviation 2.24

SECONDARY outcome

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

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant'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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 2	-1.26 units on a scale Standard Error 0.14	-1.95 units on a scale Standard Error 0.14	-1.69 units on a scale Standard Error 0.14
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 16	-2.02 units on a scale Standard Error 0.17	-2.68 units on a scale Standard Error 0.16	-2.69 units on a scale Standard Error 0.16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 4	-1.71 units on a scale Standard Error 0.15	-2.52 units on a scale Standard Error 0.15	-2.50 units on a scale Standard Error 0.15
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 8	-1.76 units on a scale Standard Error 0.15	-2.38 units on a scale Standard Error 0.15	-2.52 units on a scale Standard Error 0.15
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8, 12 and 16 Change at Week 12	-2.04 units on a scale Standard Error 2.16	-2.83 units on a scale Standard Error 0.16	-2.87 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time point.

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant'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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 32 Baseline	6.59 units on a scale Standard Deviation 0.94	6.70 units on a scale Standard Deviation 0.94	6.60 units on a scale Standard Deviation 0.89
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 32 Change at Week 32	-2.70 units on a scale Standard Deviation 2.06	-2.29 units on a scale Standard Deviation 1.95	-2.26 units on a scale Standard Deviation 2.24

SECONDARY outcome

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

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

PGA of OA was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Participants 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).

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16 Change at Week 2	-0.50 units on a scale Standard Error 0.05	-0.73 units on a scale Standard Error 0.05	-0.67 units on a scale Standard Error 0.05
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16 Change at Week 8	-0.62 units on a scale Standard Error 0.05	-0.79 units on a scale Standard Error 0.05	-0.88 units on a scale Standard Error 0.05
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16 Change at Week 12	-0.71 units on a scale Standard Error 0.06	-0.99 units on a scale Standard Error 0.06	-1.03 units on a scale Standard Error 0.06
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16 Change at Week 16	-0.64 units on a scale Standard Error 0.06	-0.78 units on a scale Standard Error 0.06	-0.90 units on a scale Standard Error 0.06
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 12 and 16 Change at Week 4	-0.60 units on a scale Standard Error 0.05	-0.85 units on a scale Standard Error 0.05	-0.93 units on a scale Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time point.

PGA of OA was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 32 Baseline	3.55 units on a scale Standard Deviation 0.62	3.61 units on a scale Standard Deviation 0.62	3.56 units on a scale Standard Deviation 0.63
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 32 Change at Week 32	-0.84 units on a scale Standard Deviation 0.87	-0.64 units on a scale Standard Deviation 0.88	-0.63 units on a scale Standard Deviation 0.91

SECONDARY outcome

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

Population: ITT population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure and 'Number analyzed' = participants evaluable for this outcome measure at specified time points.

Participants 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 or physical function subscale score; if change (improvement) from baseline to week of interest was \>=20 percent and \>=1 unit in at least 2 of the following: 1) WOMAC pain subscale score, 2) WOMAC physical function subscale score, 3) PGA of osteoarthritis. 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 \[minimum difficulty\] to 10 \[extreme difficulty\], higher score = worse physical function) and 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).

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=282 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index Week 4	53.0 percentage of participants	74.8 percentage of participants	71.8 percentage of participants
Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index Week 2	44.1 percentage of participants	63.1 percentage of participants	54.9 percentage of participants
Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index Week 8	61.9 percentage of participants	75.5 percentage of participants	75.4 percentage of participants
Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index Week 12	68.7 percentage of participants	80.9 percentage of participants	81.0 percentage of participants
Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index Week 16	64.4 percentage of participants	78.7 percentage of participants	76.1 percentage of participants
Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index Week 24	65.1 percentage of participants	76.2 percentage of participants	77.1 percentage of participants
Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index Week 32	74.0 percentage of participants	66.4 percentage of participants	63.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 16 and 24

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Overall number of participants analyzed' = Participants evaluable for this outcome measure.

WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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. 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. Percentage of participants with cumulative reduction (as percent) (greater than 0% ; \>= 10, 20, 30, 40, 50, 60, 70, 80 and 90%; = 100 %) in WOMAC pain subscale from Baseline to Weeks 16 and 24 were reported, participants (%) are reported more than once in categories specified. Missing data was imputed using mixed BOCF/LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=282 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >0%	80.1 percentage of Participants	89.7 percentage of Participants	88.4 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >0%	81.9 percentage of Participants	91.8 percentage of Participants	89.4 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=10%	77.6 percentage of Participants	87.6 percentage of Participants	82.0 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=20%	66.9 percentage of Participants	79.4 percentage of Participants	76.1 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=30%	56.2 percentage of Participants	68.1 percentage of Participants	68.7 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=40%	45.2 percentage of Participants	57.8 percentage of Participants	59.9 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=50%	35.9 percentage of Participants	49.6 percentage of Participants	47.5 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=60%	27.0 percentage of Participants	34.4 percentage of Participants	36.6 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=70%	17.1 percentage of Participants	22.3 percentage of Participants	24.3 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=80%	10.0 percentage of Participants	14.5 percentage of Participants	14.4 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: >=90%	3.2 percentage of Participants	7.4 percentage of Participants	4.9 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 16: =100%	1.1 percentage of Participants	1.8 percentage of Participants	3.2 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=10%	70.8 percentage of Participants	83.0 percentage of Participants	83.5 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=20%	65.8 percentage of Participants	76.2 percentage of Participants	76.8 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=30%	56.6 percentage of Participants	65.6 percentage of Participants	68.7 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=40%	44.8 percentage of Participants	55.0 percentage of Participants	59.2 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=50%	33.8 percentage of Participants	45.4 percentage of Participants	47.9 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=60%	24.9 percentage of Participants	33.3 percentage of Participants	36.6 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=70%	17.8 percentage of Participants	21.3 percentage of Participants	23.2 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=80%	11.4 percentage of Participants	12.1 percentage of Participants	14.1 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: >=90%	3.2 percentage of Participants	5.3 percentage of Participants	6.0 percentage of Participants
Percentage of Participants With Cumulative Percent Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16 and 24 Week 24: =100%	1.1 percentage of Participants	0.7 percentage of Participants	2.8 percentage of Participants

SECONDARY outcome

Timeframe: Week 2, 4, 8, 12, 16, 24 and 32

Population: ITT population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure and 'Number analyzed' = participants evaluable for this outcome measure at specified time points.

Percentage of participants 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, participant-relevant symptoms for pain, stiffness and physical function in participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=282 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 8: At least 70% reduction	10.7 percentage of participants	15.2 percentage of participants	22.2 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 32: At least 70% reduction	21.2 percentage of participants	12.1 percentage of participants	15.4 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 24: At least 30% reduction	56.6 percentage of participants	65.6 percentage of participants	68.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 2: At least 30% reduction	33.5 percentage of participants	46.8 percentage of participants	42.6 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 2: At least 50% reduction	16.7 percentage of participants	27.7 percentage of participants	18.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 2: At least 70% reduction	5.0 percentage of participants	10.3 percentage of participants	6.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 2: At least 90% reduction	1.1 percentage of participants	2.5 percentage of participants	1.4 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 4: At least 30% reduction	45.2 percentage of participants	61.3 percentage of participants	58.8 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 4: At least 50% reduction	22.8 percentage of participants	33.0 percentage of participants	37.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 4: At least 70% reduction	8.5 percentage of participants	13.1 percentage of participants	15.8 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 4: At least 90% reduction	1.4 percentage of participants	3.9 percentage of participants	4.9 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 8: At least 30% reduction	50.5 percentage of participants	64.2 percentage of participants	61.6 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 8: At least 50% reduction	26.0 percentage of participants	37.2 percentage of participants	44.4 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 8: At least 90% reduction	2.1 percentage of participants	4.3 percentage of participants	5.6 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 12: At least 30% reduction	58.4 percentage of participants	71.6 percentage of participants	71.1 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 12: At least 50% reduction	33.8 percentage of participants	46.8 percentage of participants	50.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 12: At least 70% reduction	15.7 percentage of participants	24.1 percentage of participants	23.2 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 12: At least 90% reduction	1.8 percentage of participants	8.5 percentage of participants	7.0 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 16: At least 30% reduction	56.2 percentage of participants	68.1 percentage of participants	68.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 16: At least 50% reduction	35.9 percentage of participants	49.6 percentage of participants	47.5 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 16: At least 70% reduction	17.1 percentage of participants	22.3 percentage of participants	24.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 16: At least 90% reduction	3.2 percentage of participants	7.4 percentage of participants	4.9 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 24: At least 50% reduction	33.8 percentage of participants	45.4 percentage of participants	47.9 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 24: At least 70% reduction	17.8 percentage of participants	21.3 percentage of participants	23.2 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 24: At least 90% reduction	3.2 percentage of participants	5.3 percentage of participants	6.0 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 32: At least 30% reduction	65.4 percentage of participants	54.7 percentage of participants	57.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 32: At least 50% reduction	43.7 percentage of participants	32.8 percentage of participants	32.9 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response Week 32: At least 90% reduction	4.8 percentage of participants	1.6 percentage of participants	4.9 percentage of participants

SECONDARY outcome

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

Population: ITT population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure and 'Number analyzed' = participants evaluable for this outcome measure at specified time points.

Percentage of participants with reduction in WOMAC physical function 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 physical function subscale. WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function:Participant's ability to move around and perform usual activities of daily living. WOMAC physical function subscale17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee/hip) during past 48 hours, calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC physical subscale on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=282 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 12: At least 90% reduction	0.7 percentage of participants	6.7 percentage of participants	5.6 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 2: At least 30% reduction	30.2 percentage of participants	44.3 percentage of participants	38.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 2: At least 50% reduction	14.6 percentage of participants	19.1 percentage of participants	18.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 2: At least 70% reduction	3.9 percentage of participants	9.2 percentage of participants	5.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 2: At least 90% reduction	1.1 percentage of participants	2.5 percentage of participants	1.8 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 4: At least 30% reduction	36.3 percentage of participants	55.0 percentage of participants	53.9 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 4: At least 50% reduction	18.1 percentage of participants	28.0 percentage of participants	32.4 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 4: At least 70% reduction	6.4 percentage of participants	11.7 percentage of participants	12.0 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 4: At least 90% reduction	1.1 percentage of participants	2.8 percentage of participants	4.6 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 8: At least 30% reduction	45.6 percentage of participants	57.4 percentage of participants	59.2 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 8: At least 50% reduction	22.8 percentage of participants	33.7 percentage of participants	37.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 8: At least 70% reduction	7.5 percentage of participants	16.0 percentage of participants	15.5 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 8: At least 90% reduction	1.4 percentage of participants	5.0 percentage of participants	4.9 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 12: At least 30% reduction	51.2 percentage of participants	67.4 percentage of participants	69.4 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 12: At least 50% reduction	27.8 percentage of participants	43.6 percentage of participants	43.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 12: At least 70% reduction	12.8 percentage of participants	19.9 percentage of participants	21.1 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 16: At least 30% reduction	53.0 percentage of participants	65.2 percentage of participants	66.2 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 16: At least 50% reduction	32.0 percentage of participants	42.9 percentage of participants	44.0 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 16: At least 70% reduction	14.2 percentage of participants	21.3 percentage of participants	18.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 16: At least 90% reduction	2.5 percentage of participants	6.0 percentage of participants	6.0 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 24: At least 30% reduction	51.2 percentage of participants	64.9 percentage of participants	68.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 24: At least 50% reduction	32.4 percentage of participants	41.5 percentage of participants	44.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 24: At least 70% reduction	14.6 percentage of participants	19.1 percentage of participants	17.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 24: At least 90% reduction	1.8 percentage of participants	5.3 percentage of participants	5.3 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 32: At least 30% reduction	60.2 percentage of participants	51.4 percentage of participants	53.7 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 32: At least 50% reduction	40.3 percentage of participants	31.2 percentage of participants	30.5 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 32: At least 70% reduction	16.9 percentage of participants	11.7 percentage of participants	11.4 percentage of participants
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >=30%, >=50%, >=70% and >=90% Response Week 32: At least 90% reduction	3.5 percentage of participants	2.0 percentage of participants	3.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 16 and 24

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Overall number of participants analyzed' = Participants evaluable for this outcome measure.

Percentage of participants with cumulative reduction (as percent) (greater than 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 which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function: participant's 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 hours, 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 from 0 (no difficulty) to 10 (extreme difficulty), higher scores indicate extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=282 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=20%	61.6 percentage of participants	73.8 percentage of participants	73.9 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=0%	79.7 percentage of participants	89.0 percentage of participants	90.1 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=80%	6.4 percentage of participants	10.6 percentage of participants	10.2 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=90%	1.8 percentage of participants	5.3 percentage of participants	5.3 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: =100%	0 percentage of participants	0.4 percentage of participants	1.8 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=0%	84.7 percentage of participants	93.6 percentage of participants	93.0 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=10%	75.1 percentage of participants	87.2 percentage of participants	83.8 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=30%	53.0 percentage of participants	65.2 percentage of participants	66.2 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=40%	44.1 percentage of participants	55.3 percentage of participants	56.0 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=50%	32.0 percentage of participants	42.9 percentage of participants	44.0 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=60%	20.3 percentage of participants	30.1 percentage of participants	30.3 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=70%	14.2 percentage of participants	21.3 percentage of participants	18.3 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=80%	7.1 percentage of participants	12.4 percentage of participants	11.3 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: >=90%	2.5 percentage of participants	6.0 percentage of participants	6.0 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 16: =100%	0.7 percentage of participants	0.7 percentage of participants	1.8 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=10%	70.1 percentage of participants	85.8 percentage of participants	84.2 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=20%	61.6 percentage of participants	74.8 percentage of participants	78.2 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=30%	51.2 percentage of participants	64.9 percentage of participants	68.7 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=40%	41.3 percentage of participants	51.1 percentage of participants	57.0 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=50%	32.4 percentage of participants	41.5 percentage of participants	44.7 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=60%	21.0 percentage of participants	30.9 percentage of participants	30.6 percentage of participants
Percentage of Participants With Cumulative Percent Change From Baseline Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16 and 24 Week 24: >=70%	14.6 percentage of participants	19.1 percentage of participants	17.3 percentage of participants

SECONDARY outcome

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

Population: ITT population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure and 'Number analyzed' = participants evaluable for this outcome measure at specified time points.

PGA of OA was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip affects you, how are you doing today?" Participants 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 participants with improvement of at least 2 points from Baseline in PGA of OA were reported. Missing data was imputed using mixed BOCF/LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=281 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=282 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis Week 2	8.5 percentage of participants	15.6 percentage of participants	12.0 percentage of participants
Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis Week 4	8.5 percentage of participants	17.7 percentage of participants	19.0 percentage of participants
Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis Week 8	12.8 percentage of participants	21.3 percentage of participants	21.8 percentage of participants
Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis Week 12	14.6 percentage of participants	26.2 percentage of participants	28.5 percentage of participants
Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis Week 16	14.6 percentage of participants	22.7 percentage of participants	27.1 percentage of participants
Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis Week 24	17.4 percentage of participants	24.1 percentage of participants	25.7 percentage of participants
Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis Week 32	19.9 percentage of participants	14.2 percentage of participants	15.4 percentage of participants

SECONDARY outcome

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

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

Participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
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 Change at Week 6	-1.48 units on a scale Standard Error 0.16	-2.38 units on a scale Standard Error 0.16	-2.43 units on a scale Standard Error 0.16
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 Change at Week 1	-0.57 units on a scale Standard Error 0.11	-1.06 units on a scale Standard Error 0.11	-0.93 units on a scale Standard Error 0.11
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 Change at Week 2	-0.98 units on a scale Standard Error 0.14	-1.72 units on a scale Standard Error 0.14	-1.49 units on a scale Standard Error 0.14
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 Change at Week 3	-1.19 units on a scale Standard Error 0.15	-1.97 units on a scale Standard Error 0.15	-1.67 units on a scale Standard Error 0.15
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 Change at Week 4	-1.37 units on a scale Standard Error 0.15	-2.28 units on a scale Standard Error 0.15	-2.13 units on a scale Standard Error 0.15
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 Change at Week 8	-1.57 units on a scale Standard Error 0.16	-2.19 units on a scale Standard Error 0.16	-2.39 units on a scale Standard Error 0.16
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 Change at Week 10	-1.79 units on a scale Standard Error 0.17	-2.51 units on a scale Standard Error 0.17	-2.56 units on a scale Standard Error 0.17
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 Change at Week 12	-1.84 units on a scale Standard Error 0.17	-2.57 units on a scale Standard Error 0.17	-2.64 units on a scale Standard Error 0.17
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 Change at Week 16	-1.98 units on a scale Standard Error 0.18	-2.50 units on a scale Standard Error 0.17	-2.61 units on a scale Standard Error 0.17
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 Change at Week 20	-2.17 units on a scale Standard Error 0.18	-2.87 units on a scale Standard Error 0.18	-2.86 units on a scale Standard Error 0.18
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 Change at Week 24	-2.21 units on a scale Standard Error 0.19	-2.60 units on a scale Standard Error 0.18	-2.73 units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, Weeks 28 and 32

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32 Baseline	6.79 units on a scale Standard Deviation 1.56	7.03 units on a scale Standard Deviation 1.38	6.90 units on a scale Standard Deviation 1.43
Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32 Change at Week 28	-2.26 units on a scale Standard Deviation 2.27	-2.63 units on a scale Standard Deviation 2.32	-2.58 units on a scale Standard Deviation 2.33
Change From Baseline for Average Pain Score in the Index Joint at Weeks 28 and 32 Change at Week 32	-2.19 units on a scale Standard Deviation 2.40	-2.07 units on a scale Standard Deviation 2.33	-2.13 units on a scale Standard Deviation 2.40

SECONDARY outcome

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

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 24	-1.97 units on a scale Standard Error 0.19	-2.59 units on a scale Standard Error 0.19	-2.84 units on a scale Standard Error 0.19
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 2	-1.25 units on a scale Standard Error 0.15	-2.03 units on a scale Standard Error 0.15	-1.90 units on a scale Standard Error 0.15
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 4	-1.90 units on a scale Standard Error 0.16	-2.62 units on a scale Standard Error 0.16	-2.74 units on a scale Standard Error 0.16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 8	-1.82 units on a scale Standard Error 0.17	-2.41 units on a scale Standard Error 0.17	-2.81 units on a scale Standard Error 0.17
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 12	-2.10 units on a scale Standard Error 0.18	-2.90 units on a scale Standard Error 0.17	-2.95 units on a scale Standard Error 0.17
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 16	-2.00 units on a scale Standard Error 0.18	-2.65 units on a scale Standard Error 0.18	-2.77 units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 32 Baseline	6.46 units on a scale Standard Deviation 1.43	6.44 units on a scale Standard Deviation 1.59	6.44 units on a scale Standard Deviation 1.53
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 32 Change at Week 32	-2.57 units on a scale Standard Deviation 2.22	-2.34 units on a scale Standard Deviation 2.18	-2.31 units on a scale Standard Deviation 2.51

SECONDARY outcome

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

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 2	-1.28 units on a scale Standard Error 0.13	-1.99 units on a scale Standard Error 0.13	-1.75 units on a scale Standard Error 0.13
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 4	-1.80 units on a scale Standard Error 0.14	-2.57 units on a scale Standard Error 0.14	-2.60 units on a scale Standard Error 0.14
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 16	-2.04 units on a scale Standard Error 0.17	-2.67 units on a scale Standard Error 0.17	-2.71 units on a scale Standard Error 0.16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 8	-1.81 units on a scale Standard Error 0.15	-2.42 units on a scale Standard Error 0.15	-2.65 units on a scale Standard Error 0.15
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 12	-2.11 units on a scale Standard Error 0.16	-2.89 units on a scale Standard Error 0.16	-2.92 units on a scale Standard Error 0.16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16 and 24 Change at Week 24	-2.11 units on a scale Standard Error 0.17	-2.66 units on a scale Standard Error 0.17	-2.83 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time point.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 32 Baseline	6.57 units on a scale Standard Deviation 0.90	6.63 units on a scale Standard Deviation 0.96	6.60 units on a scale Standard Deviation 0.91
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 32 Change at Week 32	-2.61 units on a scale Standard Deviation 1.96	-2.28 units on a scale Standard Deviation 1.87	-2.27 units on a scale Standard Deviation 2.12

SECONDARY outcome

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

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
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 Change at Week 12	-2.17 units on a scale Standard Error 0.17	-2.91 units on a scale Standard Error 0.16	-2.97 units on a scale Standard Error 0.16
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 Change at Week 16	-2.06 units on a scale Standard Error 0.18	-2.68 units on a scale Standard Error 0.17	-2.66 units on a scale Standard Error 0.17
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 Change at Week 24	-2.21 units on a scale Standard Error 0.18	-2.61 units on a scale Standard Error 0.17	-2.80 units on a scale Standard Error 0.17
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 Change at Week 2	-1.27 units on a scale Standard Error 0.14	-1.94 units on a scale Standard Error 0.14	-1.64 units on a scale Standard Error 0.14
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 Change at Week 4	-1.69 units on a scale Standard Error 0.15	-2.51 units on a scale Standard Error 0.15	-2.54 units on a scale Standard Error 0.15
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 Change at Week 8	-1.77 units on a scale Standard Error 0.16	-2.36 units on a scale Standard Error 0.15	-2.49 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
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 Change at Week 32	-2.46 units on a scale Standard Deviation 2.24	-2.01 units on a scale Standard Deviation 2.10	-1.99 units on a scale Standard Deviation 2.49
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 Baseline	6.73 units on a scale Standard Deviation 1.25	6.77 units on a scale Standard Deviation 1.27	6.79 units on a scale Standard Deviation 1.19

SECONDARY outcome

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

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo).

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
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 Change at Week 2	-1.39 units on a scale Standard Error 0.15	-2.08 units on a scale Standard Error 0.15	-1.96 units on a scale Standard Error 0.15
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 Change at Week 4	-1.76 units on a scale Standard Error 0.16	-2.73 units on a scale Standard Error 0.15	-2.72 units on a scale Standard Error 0.15
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 Change at Week 8	-1.72 units on a scale Standard Error 0.17	-2.49 units on a scale Standard Error 0.17	-2.74 units on a scale Standard Error 0.17
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 Change at Week 12	-2.17 units on a scale Standard Error 0.18	-2.92 units on a scale Standard Error 0.18	-3.05 units on a scale Standard Error 0.18
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 Change at Week 16	-2.06 units on a scale Standard Error 0.18	-2.72 units on a scale Standard Error 0.18	-2.83 units on a scale Standard Error 0.18
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 Change at Week 24	-2.32 units on a scale Standard Error 0.19	-2.76 units on a scale Standard Error 0.18	-3.04 units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, Week 32

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Week 32 Change at Week 32	-2.72 units on a scale Standard Deviation 2.32	-2.23 units on a scale Standard Deviation 2.09	-2.15 units on a scale Standard Deviation 2.41
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Going Up or Downstairs) at Week 32 Baseline	7.65 units on a scale Standard Deviation 1.13	7.79 units on a scale Standard Deviation 1.06	7.66 units on a scale Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

WPAI is 6-question participant 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline Percent Work Time Missed	9.7 units on a scale Standard Deviation 23.46	5.6 units on a scale Standard Deviation 18.33	6.9 units on a scale Standard Deviation 21.33
Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline Percent Impairment While Working	56.5 units on a scale Standard Deviation 22.26	58.9 units on a scale Standard Deviation 21.81	57.4 units on a scale Standard Deviation 18.44
Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline Percent Overall Work Impairment	59.3 units on a scale Standard Deviation 21.32	60.2 units on a scale Standard Deviation 21.20	58.3 units on a scale Standard Deviation 18.89
Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline Percent Activity Impairment	66.6 units on a scale Standard Deviation 13.35	67.7 units on a scale Standard Deviation 15.53	67.5 units on a scale Standard Deviation 13.26

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 16 and 24

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

WPAI is 6-question participant 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 16:Percent Impairment While Working	-15.92 units on a scale Standard Error 3.28	-26.23 units on a scale Standard Error 3.33	-26.48 units on a scale Standard Error 3.42
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 16: Percent Activity Impairment	-19.15 units on a scale Standard Error 1.77	-25.16 units on a scale Standard Error 1.77	-26.13 units on a scale Standard Error 1.74
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 24:Percent Impairment While Working	-15.03 units on a scale Standard Error 3.86	-19.31 units on a scale Standard Error 3.50	-17.77 units on a scale Standard Error 3.74
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 8: Percent Work Time Missed	0.04 units on a scale Standard Error 2.12	1.24 units on a scale Standard Error 2.12	-2.05 units on a scale Standard Error 2.11
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 8:Percent Impairment While Working	-13.57 units on a scale Standard Error 3.11	-20.26 units on a scale Standard Error 3.10	-26.26 units on a scale Standard Error 3.12
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 8: Percent Overall Work Impairment	-13.78 units on a scale Standard Error 3.20	-20.53 units on a scale Standard Error 3.18	-26.26 units on a scale Standard Error 3.22
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 8: Percent Activity Impairment	-15.66 units on a scale Standard Error 1.55	-21.84 units on a scale Standard Error 1.54	-24.79 units on a scale Standard Error 1.53
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 16: Percent Work Time Missed	2.36 units on a scale Standard Error 2.24	1.74 units on a scale Standard Error 2.29	-2.16 units on a scale Standard Error 2.36
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 24: Percent Overall Work Impairment	-15.17 units on a scale Standard Error 3.92	-19.03 units on a scale Standard Error 3.56	-17.29 units on a scale Standard Error 3.82
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 16: Percent Overall Work Impairment	-16.38 units on a scale Standard Error 3.33	-25.79 units on a scale Standard Error 3.37	-26.42 units on a scale Standard Error 3.47
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 24: Percent Work Time Missed	4.09 units on a scale Standard Error 3.27	2.77 units on a scale Standard Error 3.18	1.16 units on a scale Standard Error 3.27
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Impairment Scores at Weeks 8, 16 and 24 Change at Week 24: Percent Activity Impairment	-21.49 units on a scale Standard Error 1.84	-24.57 units on a scale Standard Error 1.79	-26.44 units on a scale Standard Error 1.79

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 16 and 24

Population: The intent to treat population included all randomized participants who received at least one dose of subcutaneous study medication (either tanezumab or placebo). Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

EQ-5D-5L is a standardized participant 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 participant 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 participant reports greater levels of problems across the five dimensions.

SECONDARY outcome

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

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified time points.

Heart rate was measured at sitting position.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Baseline	71.1 beats per minute Standard Deviation 8.45	70.4 beats per minute Standard Deviation 8.62	70.8 beats per minute Standard Deviation 8.33
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 2	0.2 beats per minute Standard Deviation 7.26	1.2 beats per minute Standard Deviation 7.25	0.2 beats per minute Standard Deviation 8.45
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 4	0.8 beats per minute Standard Deviation 7.92	0.9 beats per minute Standard Deviation 7.91	-0.1 beats per minute Standard Deviation 7.99
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 8	0.5 beats per minute Standard Deviation 7.61	-0.3 beats per minute Standard Deviation 8.08	-0.9 beats per minute Standard Deviation 7.54
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 12	0.9 beats per minute Standard Deviation 8.14	1.6 beats per minute Standard Deviation 8.28	0.5 beats per minute Standard Deviation 8.39
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 16	-0.3 beats per minute Standard Deviation 8.13	-0.4 beats per minute Standard Deviation 8.01	-0.0 beats per minute Standard Deviation 8.12
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 24	-0.5 beats per minute Standard Deviation 8.56	0.5 beats per minute Standard Deviation 8.77	0.4 beats per minute Standard Deviation 8.86
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 32	1.1 beats per minute Standard Deviation 8.51	0.8 beats per minute Standard Deviation 8.19	0.6 beats per minute Standard Deviation 9.40
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 48	-0.2 beats per minute Standard Deviation 8.13	1.4 beats per minute Standard Deviation 9.87	0.6 beats per minute Standard Deviation 10.01

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

A 12-lead ECG was recorded after participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 RR Interval:Change at Week 48	-19.0 millisecond Standard Deviation 118.49	-16.0 millisecond Standard Deviation 112.48	-26.7 millisecond Standard Deviation 125.81
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 PR Interval: Baseline	168.7 millisecond Standard Deviation 23.95	165.6 millisecond Standard Deviation 21.92	168.0 millisecond Standard Deviation 24.54
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QT Interval: Baseline	402.0 millisecond Standard Deviation 28.45	403.1 millisecond Standard Deviation 29.92	405.6 millisecond Standard Deviation 26.84
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QT Interval:Change at Week 24	-2.2 millisecond Standard Deviation 22.65	-3.1 millisecond Standard Deviation 21.78	-3.8 millisecond Standard Deviation 25.84
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QT Interval:Change at Week 48	-2.5 millisecond Standard Deviation 23.27	-1.6 millisecond Standard Deviation 24.40	-4.9 millisecond Standard Deviation 24.06
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QTCB Interval: Baseline	419.8 millisecond Standard Deviation 22.32	421.3 millisecond Standard Deviation 20.78	422.5 millisecond Standard Deviation 20.57
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QTCB Interval:Change at Week 24	-1.5 millisecond Standard Deviation 17.56	0.2 millisecond Standard Deviation 18.47	0.0 millisecond Standard Deviation 16.26
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 RR Interval: Baseline	923.9 millisecond Standard Deviation 124.86	923.6 millisecond Standard Deviation 139.69	928.3 millisecond Standard Deviation 126.14
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 RR Interval:Change at Week 24	-3.2 millisecond Standard Deviation 108.30	-14.6 millisecond Standard Deviation 119.62	-16.1 millisecond Standard Deviation 124.65
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 PR Interval:Change at Week 24	0.1 millisecond Standard Deviation 14.07	0.5 millisecond Standard Deviation 13.38	2.0 millisecond Standard Deviation 15.43
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 PR Interval:Change at Week 48	1.3 millisecond Standard Deviation 13.64	-1.1 millisecond Standard Deviation 14.38	-0.4 millisecond Standard Deviation 14.23
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QRS Interval: Baseline	95.7 millisecond Standard Deviation 12.69	95.6 millisecond Standard Deviation 14.05	95.8 millisecond Standard Deviation 14.48
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QRS Interval:Change at Week 24	-0.2 millisecond Standard Deviation 7.22	0.2 millisecond Standard Deviation 7.57	0.0 millisecond Standard Deviation 7.34
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QRS Interval:Change at Week 48	-0.2 millisecond Standard Deviation 8.04	0.2 millisecond Standard Deviation 8.33	0.8 millisecond Standard Deviation 8.73
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QTCB Interval:Change at Week 48	1.5 millisecond Standard Deviation 16.45	1.7 millisecond Standard Deviation 16.70	1.8 millisecond Standard Deviation 16.80
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QTCF Interval: Baseline	413.6 millisecond Standard Deviation 20.70	414.9 millisecond Standard Deviation 19.23	416.6 millisecond Standard Deviation 18.61
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QTCF Interval:Change at Week 24	-1.7 millisecond Standard Deviation 15.72	-1.0 millisecond Standard Deviation 14.94	-1.3 millisecond Standard Deviation 15.05
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 24 and 48 QTCF Interval:Change at Week 48	0.2 millisecond Standard Deviation 14.50	0.5 millisecond Standard Deviation 15.58	-0.5 millisecond Standard Deviation 13.96

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Heart rate was measured at sitting position.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 24 and 48 Change at Week 48	1.4 beats per minute Standard Deviation 8.59	1.1 beats per minute Standard Deviation 8.98	2.3 beats per minute Standard Deviation 10.44
Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 24 and 48 Baseline	66.2 beats per minute Standard Deviation 9.28	66.5 beats per minute Standard Deviation 10.69	65.9 beats per minute Standard Deviation 9.22
Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 24 and 48 change at Week 24	0.3 beats per minute Standard Deviation 8.05	0.9 beats per minute Standard Deviation 9.15	1.4 beats per minute Standard Deviation 10.19

SECONDARY outcome

Timeframe: Baseline up to Week 48

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously. Here, 'Overall number of participants analyzed' signifies participants analyzed by adjudication committee.

Incidence of participants 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.

Outcome measures

Outcome measures
Measure	Placebo n=19 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=27 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=33 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Percentage of Participants With Adjudicated Joint Safety Outcomes Composite Joint Safety Endpoint	0 percentage of participants Interval 0.0 to 1.3	1.8 percentage of participants Interval 0.6 to 4.1	3.2 percentage of participants Interval 1.5 to 5.9
Percentage of Participants With Adjudicated Joint Safety Outcomes Rapidly Progressive OA	0 percentage of participants Interval 0.0 to 1.3	1.4 percentage of participants Interval 0.4 to 3.6	2.8 percentage of participants Interval 1.2 to 5.5
Percentage of Participants With Adjudicated Joint Safety Outcomes Rapidly Progressive OA type 1	0 percentage of participants Interval 0.0 to 1.3	1.1 percentage of participants Interval 0.2 to 3.1	1.8 percentage of participants Interval 0.6 to 4.1
Percentage of Participants With Adjudicated Joint Safety Outcomes Rapidly Progressive OA type 2	0 percentage of participants Interval 0.0 to 1.3	0.4 percentage of participants Interval 0.0 to 2.0	1.1 percentage of participants Interval 0.2 to 3.1
Percentage of Participants With Adjudicated Joint Safety Outcomes Primary Osteonecrosis	0 percentage of participants Interval 0.0 to 1.3	0 percentage of participants Interval 0.0 to 1.3	0.4 percentage of participants Interval 0.0 to 1.9
Percentage of Participants With Adjudicated Joint Safety Outcomes Pathological Fracture	0 percentage of participants Interval 0.0 to 1.3	0 percentage of participants Interval 0.0 to 1.3	0 percentage of participants Interval 0.0 to 1.3
Percentage of Participants With Adjudicated Joint Safety Outcomes Subchondral Insufficiency Fracture	0 percentage of participants Interval 0.0 to 1.3	0.4 percentage of participants Interval 0.0 to 2.0	0 percentage of participants Interval 0.0 to 1.3

SECONDARY outcome

Timeframe: Baseline up to Week 48

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously.

Percentage of participants who underwent at least one total knee, hip or shoulder joint replacement surgery.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Percentage of Participants With Total Joint Replacements	6.7 percentage of participants Interval 4.1 to 10.3	7.8 percentage of participants Interval 4.9 to 11.5	7.0 percentage of participants Interval 4.4 to 10.7

SECONDARY outcome

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

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously. Here, 'Overall number of participants analyzed' signifies participants analyzed for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=242 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=228 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Number of Participants With Confirmed Orthostatic Hypotension Week 8	0 Participants	0 Participants	1 Participants
Number of Participants With Confirmed Orthostatic Hypotension Week 12	0 Participants	0 Participants	0 Participants
Number of Participants With Confirmed Orthostatic Hypotension Week 24	0 Participants	0 Participants	0 Participants
Number of Participants With Confirmed Orthostatic Hypotension Baseline	0 Participants	1 Participants	0 Participants
Number of Participants With Confirmed Orthostatic Hypotension Week 2	0 Participants	0 Participants	0 Participants
Number of Participants With Confirmed Orthostatic Hypotension Week 4	0 Participants	0 Participants	1 Participants
Number of Participants With Confirmed Orthostatic Hypotension Week 16	0 Participants	0 Participants	1 Participants
Number of Participants With Confirmed Orthostatic Hypotension Week 32	0 Participants	0 Participants	0 Participants
Number of Participants With Confirmed Orthostatic Hypotension Week 48	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

The SAS is a 12 item (11 for females) questionnaire, from which the total number of symptoms (0-12 for males and 0-11 for females) is calculated. Each positive symptom is rated from 1 (not at all) to 5 (a lot). The total impact score was the sum of all symptom rating scores, with 0 assigned where the participant 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Week 24 Number of symptoms reported: Baseline	0.55 units on a scale Standard Deviation 0.85	0.53 units on a scale Standard Deviation 0.85	0.55 units on a scale Standard Deviation 0.83
Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Week 24 Number of symptoms reported: Change at Week 24	0.03 units on a scale Standard Deviation 1.07	0.15 units on a scale Standard Deviation 1.18	0.18 units on a scale Standard Deviation 1.22
Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Week 24 Total Symptom Impact Score: Baseline	1.14 units on a scale Standard Deviation 1.94	1.11 units on a scale Standard Deviation 1.79	1.20 units on a scale Standard Deviation 1.99
Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Week 24 Total Symptom Impact Score: Change at Week 24	0.32 units on a scale Standard Deviation 2.92	0.53 units on a scale Standard Deviation 3.23	0.56 units on a scale Standard Deviation 3.11

SECONDARY outcome

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

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

NIS is a standardized instrument used to evaluate participant 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.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 4	0.01 units on a scale Standard Deviation 1.16	0.00 units on a scale Standard Deviation 1.31	-0.32 units on a scale Standard Deviation 1.24
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Baseline	1.35 units on a scale Standard Deviation 2.85	1.35 units on a scale Standard Deviation 3.72	1.48 units on a scale Standard Deviation 3.11
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 2	0.03 units on a scale Standard Deviation 0.92	-0.09 units on a scale Standard Deviation 0.68	-0.21 units on a scale Standard Deviation 1.14
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 8	-0.11 units on a scale Standard Deviation 1.42	-0.13 units on a scale Standard Deviation 1.20	-0.41 units on a scale Standard Deviation 1.56
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 12	-0.12 units on a scale Standard Deviation 1.38	-0.03 units on a scale Standard Deviation 1.50	-0.39 units on a scale Standard Deviation 1.59
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 16	-0.17 units on a scale Standard Deviation 1.59	-0.03 units on a scale Standard Deviation 1.72	-0.46 units on a scale Standard Deviation 1.53
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 24	-0.20 units on a scale Standard Deviation 1.51	-0.01 units on a scale Standard Deviation 1.85	-0.47 units on a scale Standard Deviation 1.58
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 32	-0.23 units on a scale Standard Deviation 1.69	0.00 units on a scale Standard Deviation 1.75	-0.41 units on a scale Standard Deviation 1.57
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 Change at Week 48	-0.22 units on a scale Standard Deviation 1.67	0.01 units on a scale Standard Deviation 1.91	-0.43 units on a scale Standard Deviation 1.57

SECONDARY outcome

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

Population: The safety population was defined as all participants treated with tanezumab or placebo subcutaneously. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a semi quantitative enzyme linked immunosorbent assay (ELISA). Participants listed as having anti-tanezumab antibodies had ADA titer level \>=3.32. Less than 3.32 was considered below the limit of quantitation.

Outcome measures

Outcome measures
Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Number of Participants With Anti Tanezumab Antibodies Week 8	24 Participants	27 Participants	41 Participants
Number of Participants With Anti Tanezumab Antibodies Week 24	19 Participants	39 Participants	49 Participants
Number of Participants With Anti Tanezumab Antibodies Week 32	19 Participants	38 Participants	42 Participants
Number of Participants With Anti Tanezumab Antibodies Baseline	24 Participants	26 Participants	36 Participants
Number of Participants With Anti Tanezumab Antibodies Week 16	25 Participants	34 Participants	48 Participants
Number of Participants With Anti Tanezumab Antibodies Week 48	18 Participants	32 Participants	31 Participants

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 77 other events

Deaths: 0 deaths

Tanezumab 2.5 mg

Serious events: 8 serious events

Other events: 73 other events

Deaths: 1 deaths

Tanezumab 5 mg

Serious events: 9 serious events

Other events: 60 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=282 participants at risk Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 participants at risk Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 participants at risk Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Infections and infestations Nasopharyngitis	8.9% 25/282 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.	11.0% 31/283 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.	7.4% 21/284 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.
Musculoskeletal and connective tissue disorders Arthralgia	12.1% 34/282 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.	9.5% 27/283 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.	7.7% 22/284 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.
Musculoskeletal and connective tissue disorders Back pain	5.3% 15/282 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.	5.7% 16/283 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.	6.0% 17/284 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.
Nervous system disorders Headache	6.4% 18/282 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.	5.3% 15/283 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.	4.9% 14/284 • Baseline up to Week 24 Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as nonserious in another participant or 1 participant may have experienced both serious and nonserious event during study. One death was accounted as lost to follow-up in participant flow as the death was not confirmed by family nor a doctor, but a follow-up letter to the participant was returned with a note on the envelope that the addressee died.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 24: Mobility	2.4 units on a scale Standard Deviation 0.78	2.3 units on a scale Standard Deviation 0.84	2.3 units on a scale Standard Deviation 0.84
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 24: Self-care	1.7 units on a scale Standard Deviation 0.83	1.7 units on a scale Standard Deviation 0.77	1.6 units on a scale Standard Deviation 0.76
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 8: Mobility	2.6 units on a scale Standard Deviation 0.82	2.3 units on a scale Standard Deviation 0.83	2.3 units on a scale Standard Deviation 0.80
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 8: Self-care	2.0 units on a scale Standard Deviation 0.90	1.8 units on a scale Standard Deviation 0.80	1.6 units on a scale Standard Deviation 0.78
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 8: Usual activities	2.5 units on a scale Standard Deviation 0.78	2.3 units on a scale Standard Deviation 0.82	2.2 units on a scale Standard Deviation 0.78
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 8: Pain/Discomfort	2.7 units on a scale Standard Deviation 0.85	2.5 units on a scale Standard Deviation 0.80	2.4 units on a scale Standard Deviation 0.79
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 16: Usual activities	2.3 units on a scale Standard Deviation 0.81	2.2 units on a scale Standard Deviation 0.78	2.1 units on a scale Standard Deviation 0.84
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 16: Pain/Discomfort	2.5 units on a scale Standard Deviation 0.82	2.3 units on a scale Standard Deviation 0.80	2.3 units on a scale Standard Deviation 0.80
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 16: Anxiety/Depression	1.4 units on a scale Standard Deviation 0.78	1.3 units on a scale Standard Deviation 0.61	1.4 units on a scale Standard Deviation 0.68
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 24: Usual activities	2.3 units on a scale Standard Deviation 0.78	2.2 units on a scale Standard Deviation 0.82	2.2 units on a scale Standard Deviation 0.82
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 24: Pain/Discomfort	2.5 units on a scale Standard Deviation 0.81	2.4 units on a scale Standard Deviation 0.78	2.4 units on a scale Standard Deviation 0.77
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 24: Anxiety/Depression	1.4 units on a scale Standard Deviation 0.67	1.4 units on a scale Standard Deviation 0.71	1.4 units on a scale Standard Deviation 0.68
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Baseline: Mobility	3.1 units on a scale Standard Deviation 0.63	3.1 units on a scale Standard Deviation 0.62	3.2 units on a scale Standard Deviation 0.65
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Baseline: Self-care	2.4 units on a scale Standard Deviation 0.92	2.3 units on a scale Standard Deviation 0.92	2.3 units on a scale Standard Deviation 0.90
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Baseline: Usual activities	3.0 units on a scale Standard Deviation 0.65	3.0 units on a scale Standard Deviation 0.68	3.0 units on a scale Standard Deviation 0.68
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Baseline: Pain/Discomfort	3.3 units on a scale Standard Deviation 0.72	3.2 units on a scale Standard Deviation 0.73	3.3 units on a scale Standard Deviation 0.69
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Baseline: Anxiety/Depression	1.7 units on a scale Standard Deviation 0.87	1.7 units on a scale Standard Deviation 0.88	1.7 units on a scale Standard Deviation 0.87
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 8: Anxiety/Depression	1.5 units on a scale Standard Deviation 0.80	1.4 units on a scale Standard Deviation 0.64	1.4 units on a scale Standard Deviation 0.71
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 16: Mobility	2.4 units on a scale Standard Deviation 0.88	2.2 units on a scale Standard Deviation 0.84	2.2 units on a scale Standard Deviation 0.84
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score Week 16: Self-care	1.8 units on a scale Standard Deviation 0.88	1.7 units on a scale Standard Deviation 0.78	1.6 units on a scale Standard Deviation 0.80

Measure	Placebo n=282 Participants Placebo matched to tanezumab (RN624 or PF-04383119) injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 2.5 mg n=283 Participants Tanezumab (RN624 or PF-04383119) 2.5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.	Tanezumab 5 mg n=284 Participants Tanezumab (RN624 or PF-04383119) 5 mg injection administered subcutaneously on Day 1 (Baseline), Week 8 and Week 16.
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP:Change at Week 2	-1.0 millimeters of mercury (mmHg) Standard Deviation 10.26	-2.0 millimeters of mercury (mmHg) Standard Deviation 11.24	-2.4 millimeters of mercury (mmHg) Standard Deviation 11.24
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP:Change at Week 4	-0.3 millimeters of mercury (mmHg) Standard Deviation 11.09	-2.0 millimeters of mercury (mmHg) Standard Deviation 10.94	-2.4 millimeters of mercury (mmHg) Standard Deviation 11.52
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP: Baseline	132.0 millimeters of mercury (mmHg) Standard Deviation 13.54	132.7 millimeters of mercury (mmHg) Standard Deviation 12.59	132.0 millimeters of mercury (mmHg) Standard Deviation 12.12
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP:Change at Week 8	-0.8 millimeters of mercury (mmHg) Standard Deviation 10.89	-2.1 millimeters of mercury (mmHg) Standard Deviation 10.63	-2.5 millimeters of mercury (mmHg) Standard Deviation 12.07
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP:Change at Week 12	-1.2 millimeters of mercury (mmHg) Standard Deviation 11.38	-1.8 millimeters of mercury (mmHg) Standard Deviation 11.53	-2.8 millimeters of mercury (mmHg) Standard Deviation 11.64
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP:Change at Week 16	-0.4 millimeters of mercury (mmHg) Standard Deviation 12.18	-1.6 millimeters of mercury (mmHg) Standard Deviation 12.92	-2.3 millimeters of mercury (mmHg) Standard Deviation 11.63
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP:Change at Week 24	-1.5 millimeters of mercury (mmHg) Standard Deviation 11.47	-2.0 millimeters of mercury (mmHg) Standard Deviation 12.55	-2.5 millimeters of mercury (mmHg) Standard Deviation 12.11
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP:Change at Week 32	-2.1 millimeters of mercury (mmHg) Standard Deviation 12.61	-1.8 millimeters of mercury (mmHg) Standard Deviation 12.40	-1.0 millimeters of mercury (mmHg) Standard Deviation 12.55
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 SBP:Change at Week 48	-0.7 millimeters of mercury (mmHg) Standard Deviation 10.38	-1.7 millimeters of mercury (mmHg) Standard Deviation 11.60	-1.8 millimeters of mercury (mmHg) Standard Deviation 11.34
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP: Baseline	79.7 millimeters of mercury (mmHg) Standard Deviation 8.28	79.3 millimeters of mercury (mmHg) Standard Deviation 8.45	79.5 millimeters of mercury (mmHg) Standard Deviation 8.10
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP:Change at Week 2	-0.4 millimeters of mercury (mmHg) Standard Deviation 6.81	-1.7 millimeters of mercury (mmHg) Standard Deviation 7.18	-1.7 millimeters of mercury (mmHg) Standard Deviation 7.33
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP:Change at Week 4	-0.6 millimeters of mercury (mmHg) Standard Deviation 7.06	-1.7 millimeters of mercury (mmHg) Standard Deviation 7.35	-1.8 millimeters of mercury (mmHg) Standard Deviation 7.85
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP:Change at Week 8	-0.1 millimeters of mercury (mmHg) Standard Deviation 7.59	-1.0 millimeters of mercury (mmHg) Standard Deviation 7.11	-1.7 millimeters of mercury (mmHg) Standard Deviation 7.65
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP:Change at Week 12	-1.0 millimeters of mercury (mmHg) Standard Deviation 7.44	-1.3 millimeters of mercury (mmHg) Standard Deviation 7.79	-2.8 millimeters of mercury (mmHg) Standard Deviation 7.94
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP:Change at Week 16	-0.7 millimeters of mercury (mmHg) Standard Deviation 7.85	-0.6 millimeters of mercury (mmHg) Standard Deviation 8.26	-1.8 millimeters of mercury (mmHg) Standard Deviation 7.90
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP:Change at Week 24	-0.1 millimeters of mercury (mmHg) Standard Deviation 7.81	-0.2 millimeters of mercury (mmHg) Standard Deviation 8.42	-2.0 millimeters of mercury (mmHg) Standard Deviation 7.90
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP:Change at Week 32	-1.2 millimeters of mercury (mmHg) Standard Deviation 8.52	-0.7 millimeters of mercury (mmHg) Standard Deviation 8.06	-1.5 millimeters of mercury (mmHg) Standard Deviation 8.64
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 32 and 48 DBP:Change at Week 48	-0.6 millimeters of mercury (mmHg) Standard Deviation 7.22	-0.7 millimeters of mercury (mmHg) Standard Deviation 8.32	-0.9 millimeters of mercury (mmHg) Standard Deviation 8.17