A Phase 3 Study of Tanezumab for Chronic Low Back Pain

Phase 3

Completed

Conditions: Low Back Pain

Interventions: Biological: Tanezumab 10 mg SC
Biological: Placebo to Week 16; tanezumab 5mg SC
Biological: Placebo to Week 16, tanezumab 10 mg SC
Biological: Tanezumab 5 mg SC
Biological: Tramadol PR oral

Registration Number: NCT02528253

Lead Sponsor: Pfizer

Brief Summary: This study will investigate the efficacy and safety of tanezumab 5 mg and 10 mg administered by subcutaneous injection seven times at 8 week intervals (56 weeks). The primary objective of this study is to evaluate the effectiveness of tanezumab 10 mg and 5 mg compared to placebo for the treatment of chronic low back pain. Secondary objectives are to evaluate the long-term safety and effectiveness of tanezumab 10 mg and 5 mg compared to placebo for the treatment of chronic low back pain. In addition, the study will evaluate the effectiveness and long term safety profile of tanezumab treatment for chronic low back pain compared to tramadol Prolonged Release (PR), a medication commonly utilized for the treatment of chronic low back pain.

Detailed Description: This is a randomized, double blind, placebo and active controlled, multicenter, parallel group Phase 3 study of the efficacy and safety of tanezumab when administered by SC injection for up to 56 weeks in subjects with chronic low back pain. Approximately 1800 subjects will be randomized to 1 of 4 treatment groups in a 2:2:2:3 ratio (ie, 400 subjects per treatment group for the placebo, tanezumab 5 mg and tanezumab 10 mg treatment groups and 600 subjects in the tramadol PR treatment group). Treatment groups will include: 1.) Placebo administered SC at an 8 week interval plus placebo matching tramadol PR up to Week 16. At the Week 16 visit, subjects in this group who meet the efficacy responder criteria will be switched in a blinded fashion in a 1:1 ratio to either tanezumab 5 mg or tanezumab 10 mg administered SC at an 8 week interval plus placebo matching tramadol PR to Week 56; 2.)Tanezumab 5 mg SC administered at an 8 week interval plus placebo matching tramadol PR to Week 56; 3.) Tanezumab 10 mg SC administered at an 8 week interval plus placebo matching tramadol PR to Week 56; 4.) Oral tramadol PR plus placebo administered SC at an 8 week interval to Week 56. The study is designed with a total duration (post randomization) of up to 80 weeks and will consist of three periods: Screening (up to a maximum of 37 days; includes a Washout Period and an Initial Pain Assessment Period), a Double blind Treatment Period (comprised of a 16 week Primary Efficacy Phase and a 40 week Long Term Safety and Efficacy Phase), and a Follow up Period (24 weeks). The Screening Period (beginning up to 37 days prior to Randomization) includes a Washout Period (lasting 2 32 days), if required, and an Initial Pain Assessment Period (the 5 days prior to Randomization/Baseline). Prior to entering the study, subjects must have a documented history of previous inadequate treatment response to medications in 3 different categories of agents commonly used to treat and generally considered effective for the treatment of chronic low back pain.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1832

Inclusion Criteria

-Chronic low back pain ≥3 months in duration, Quebec Task Force in Spinal Disorders class 1 or 2, with documented history of previous inadequate treatment response to at least 3 different categories of agents commonly used and generally considered effective for the treatment of chronic low back pain.

Exclusion Criteria

--Diagnosis of osteoarthritis of the knee or hip as defined by the American College of Rheumatology (ACR) criteria.

Subjects who have Kellgren Lawrence Grade > or =2 radiographic evidence of hip or Grade > or=3 radiographic evidence of knee osteoarthritis will be excluded;
History or radiographic evidence of other diseases that could confound efficacy or safety assessments (e.g., rheumatoid arthritis).
History or radiographic evidence of orthopedic conditions that may increase the risk of, or confound assessment of joint safety conditions during the study.
Signs and symptoms of clinically significant cardiac disease within 6 months of the study (e.g., unstable angina, myocardial infarction, resting bradycardia, poorly controlled or untreated hypertension) as defined in the protocol or subjects with any other cardiovascular illness that in the opinion of the Investigator would render a subject unsuitable to participate in the study
History, diagnosis, or signs and symptoms of clinically significant neurological disease (e.g., transient ischemic attack, stroke, peripheral or autonomic neuropathy) as specified in the protocol
Subjects with evidence or symptoms consistent with autonomic dysfunction (e.g., orthostatic hypotension and/or autonomic symptoms) as defined in the protocol.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tanezumab 10 mg SC	Tanezumab 10 mg SC	-
Placebo to Week 16; tanezumab 5 mg SC	Placebo to Week 16; tanezumab 5mg SC	-
Placebo to Week 16, tanezumab 10 mg SC	Placebo to Week 16, tanezumab 10 mg SC	-
Tanezumab 5 mg SC	Tanezumab 5 mg SC	-
Tramadol PR oral	Tramadol PR oral	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Placebo at Week 16	Baseline, Week 16	Average low back pain was assessed on an 11-point numeric rating scale (NRS) captured through an interactive response technology (IRT). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) at Week 16 for Tanezumab Versus (Vs) Placebo	Baseline, Week 16	The RMDQ is a self-administered, widely used health status measure index of how well participants with low back pain (LBP) are able to function with regard to daily activities. It measures pain and function, using 24 items describing limitations to everyday life that can be caused by LBP. The total score of the RMDQ from the total number of items checked ranged from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater disability.
Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 64	Baseline, Week 64	Average LBP was assessed on an 11-point NRS captured through an IRT. The LBPI score was captured once a week for week 64. Participants described their average LBP during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain.
Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Total Score at Weeks 2, 4, 8, 16 (for Tanezumab vs Tramadol) 24, 32, 40, 48 and 56	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	The RMDQ is a self-administered, widely used health status measure index of how well participants with LBP are able to function with regard to daily activities. It measures pain and function, using 24 items describing limitations to everyday life that can be caused by LBP. The total score of the RMDQ is the total number of items checked ranging from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater disability. Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 64 and 80: Observed Data	Baseline, Weeks 64 and 80	The RMDQ is a self-administered, widely used health status measure index of how well participants with LBP are able to function with regard to daily activities. It measures pain and function, using 24 items describing limitations to everyday life that can be caused by LBP. The total score of the RMDQ is the total number of items checked ranging from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater disability.
Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	PGA of LBP was assessed by asking a question to participants: "Considering all the ways your low back pain affects you, how are you doing today?" Participants responded on a 5 point Likert scale ranging from 1-5, using IRT, where 1=very good (asymptomatic and no limitation of normal activities); 2=good (mild symptoms and no limitation of normal activities); 3=fair (moderate symptoms and limitation of some normal activities); 4=poor (severe symptoms and inability to carry out most normal activities); and 5=very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher scores indicated worsening of condition. Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Percentage of Participants Achieving Average LBPI Reduction of >=30 Percent(%), >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)	Baseline, Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56	Average LBP was assessed on an 11-point NRS captured through an IRT. The LBPI score was captured once a week for week 64. Participants described their average LBP during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Percentage of participants with reduction in LBPI of at least (\>=) 30%, 50%, 70% and 90% at weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56 compared to baseline were classified as responders to LBPI and are reported here, participants (%) are reported more than once in categories specified.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.Also, intent of study was to compare tanezumab Vs placebo for data up to \& including W16 \& comparisons of tanezumab Vs tramadol for data up to \& including W56.
Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain at Week 64: Observed Data	Baseline, Week 64	PGA of LBP was assessed by asking a question to participants: "Considering all the ways your low back pain affects you, how are you doing today?" Participants responded on a 5 point Likert scale ranging from 1-5, using IRT, where 1=very good (asymptomatic and no limitation of normal activities); 2=good (mild symptoms and no limitation of normal activities); 3=fair (moderate symptoms and limitation of some normal activities); 4=poor (severe symptoms and inability to carry out most normal activities); and 5=very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Percentage of Participants Achieving RMDQ Reduction of >=30%, >=50%, >=70% and >=90% From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	RMDQ: health status measure index of how well participants with LBP are able to function with regard to daily activities. Measures pain and function using 24 items describing limitations to everyday life. Total score of RMDQ is total number of items checked ranging from 0=no disability to 24=maximum disability, higher scores=greater disability. Percentage of participants with reduction in LBPI of at least (\>=) 30, 50, 70 and 90% at specified weeks compared to baseline were classified as responders to LBPI and are reported here. Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms. Also, intent of study was to compare tanezumab Vs placebo for data up to \& including W16 \& comparisons of tanezumab Vs tramadol for data up to \& including W56.
Percentage of Participants With Cumulative Percent Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) Score at Weeks 16, 24 and 56	Baseline, Weeks 16, 24 and 56	The RMDQ is a self-administered, widely used health status measure index of how well participants with LBP are able to function with regard to daily activities. It measures pain and function, using 24 items describing limitations to everyday life that can be caused by LBP. The total score of the RMDQ is the total number of items checked ranging from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater disability. Percentage of participants with cumulative reduction (as percent) (\>0 %; \>= 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90% and =100 %) in RMDQ from Baseline to weeks 16, 24 and 56 were reported, participants (%) are reported more than once in categories specified.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Worst Pain at Week 64: Observed Data	Baseline, Week 64	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4 of pain at its 'worst', 'least', 'average' and 'right now'. For the Worst Pain item of the BPI-sf scale (11 point NRS scale; range: 0 \[no pain\] to 10 \[pain as bad as you can imagine\]), participants were asked to rate their pain by marking an "X" in one of the boxes that best described their pain at its worst, during 24 hours prior to evaluation, higher scores indicated greater pain severity. Question 5 (7-items) assessed level of pain interference on daily activities.
Change From Baseline in Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Tramadol at Week 16	Baseline, Week 16	Average LBP was assessed on an 11-point NRS captured through an IRT. Participants described their average LBP during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain.
Change From Baseline in Average Low Back Pain Intensity (LBPI) Score at Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56	Baseline, Weeks 2, 4, 8, 12, 24, 32, 40, 48 and 56	Average LBP was assessed on an 11-point NRS captured through an IRT. The LBPI score was captured once daily from baseline up to week 16, and once weekly from week 16 to week 64. Participants described their average LBP during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Percentage of Participants With Cumulative Percent Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Weeks 16, 24 and 56: Mixed Baseline Observation Carried Forward (BOCF)/Last Observation Carried Forward (LOCF)	Baseline, Weeks 16, 24 and 56	Average LBP was assessed on an 11-point NRS captured through an IRT. LBPI score was captured once a week for week 64. Participants described their average LBP during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain.Percentage of participants with cumulative reduction (as percent) (greater than \[\>\] 0%; \>= 10, 20, 30, 40, 50, 60, 70, 80, 90 and equals to \[=\] 100 %) in LBPI from baseline to weeks 16, 24 and 56 were reported, participants (%) are reported more than once in categories specified.Missing data was imputed using mixed BOCF/LOCF.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.Also, intent of study was to compare tanezumab Vs placebo for data up to \& including W16 \& comparisons of tanezumab Vs tramadol for data up to \& including W56.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Scores Average Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4 of pain at its 'worst', 'least', 'average' and 'right now'. For the Average Pain item of the BPI-sf scale (11 point NRS scale; range: 0 \[no pain\] to 10 \[pain as bad as you can imagine\]), participants were asked to rate their pain by marking an "X" in one of the boxes that best described their pain during 24 hours prior to evaluation, higher scores indicated greater pain severity. Question 5 (7-items) assessed level of pain interference on daily activities.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference Index at Week 64: Observed Data	Baseline, Week 64	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Walking Ability at Week 64: Observed Data	Baseline, Week 64	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.
Number of Participants Who Responded for Chronic Low Back Pain Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	Chronic Low Back Pain Responder Index analysis is a composite endpoint of average low back pain intensity (aLBPI) score, PGA of Low Back Pain, and RMDQ total score. Participants were successful responders if they had: \>=30 percent reduction in mean daily average LBPI from baseline to particular week; decrease of \>=30 percent in PGA of low back pain from baseline to particular week or no worsening (increase) in RMDQ total score from baseline to particular week. Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms. Also, intent of study was to compare tanezumab Vs placebo for data up to \& including W16 \& comparisons of tanezumab Vs tramadol for data up to \& including W56.
Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64	Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 56 and 64	In case of inadequate pain relief, acetaminophen/paracetamol caplets, tablets, or capsules up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between day 1 and week 56. Number of participants with any use of rescue medication during the particular study week were summarized. As pre specified intent of study, for analyses after week 16 where multiple imputation was used, data was reported per 3 arms. This is because participants who received placebo from Day 1 and received tanezumab 5/10 mg at week 16, received placebo for the first 16 weeks, and their data before week 16 were not be imputed into analyses after week 16.
Change From Baseline in Brief Pain Inventory-short Form (BPI-sf) Score Worst Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4 of pain at its 'worst', 'least', 'average' and 'right now'. For the Worst Pain item of the BPI-sf scale (11 point NRS scale; range: 0 \[no pain\] to 10 \[pain as bad as you can imagine\]), participants were asked to rate their pain by marking an "X" in one of the boxes that best described their pain at its worst, during 24 hours prior to evaluation, higher scores indicated greater pain severity. Question 5 (7-items) assessed level of pain interference on daily activities.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Normal Work at Week 64: Observed Data	Baseline, Week 64	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Average Pain at Week 64: Observed Data	Baseline, Week 64	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4 of pain at its 'worst', 'least', 'average' and 'right now'. For the Average Pain item of the BPI-sf scale (11 point NRS scale; range: 0 \[no pain\] to 10 \[pain as bad as you can imagine\]), participants were asked to rate their pain by marking an "X" in one of the boxes that best described their pain during 24 hours prior to evaluation, higher scores indicated greater pain severity. Question 5 (7-items) assessed level of pain interference on daily activities.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Walking Ability at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Sleep at Week 64: Observed Data	Baseline, Week 64	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Normal Work at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Number of Participants Who Withdrew Due to Lack of Efficacy	Baseline up to Week 56	Number of participants who withdrew from treatment due to lack of efficacy have been reported here.
Number of Participants Who Took Rescue Medication During Week 64: Observed Data	Week 64	In case of inadequate pain relief, after Week 24, acetaminophen/paracetamol up to 4000 mg per day up to 5 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of participants with any use of rescue medication during the 4 weeks up to and including the particular study week were summarized.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With Sleep at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value	Baseline, Weeks 8, 16, 24, 40, 56 and 64	EQ-5D-5L: 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 2 components: a health state profile and an optional VAS.EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.Individual dimension scores ranged from 1.0(least impairment of health state) to 5.0(most impairment of health state). Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems.Responses from five domains were used to calculate a single utility index (Overall health utility score) where values are less than equal to (\<=) 1.Overall 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 reduced where participant reports greater levels of problems across five dimensions.
Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Baseline: Observed Data	Baseline	WPAI: LBP is 6-question participant rated questionnaire that measures the effect of participant's chronic low back pain (CLBP) on general health and symptom severity on work productivity and regular activities. It yields 4 sub-scores: work time missed due to pain (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. Pre-specified intent of study for efficacy data up to Week 16 was to analyze, participants who received placebo from Day 1 and received tanezumab 5/10 mg at week 16 in placebo arm, in pooled manner. Hence data have been reported per four arms.
Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Low Back Pain (WPAI:LBP) Scores at Weeks 16, 56 and 64	Baseline, Weeks 16, 56 and 64	WPAI: LBP is 6-question participant rated questionnaire that measures the effect of participant's chronic low back pain (CLBP) on general health and symptom severity on work productivity and regular activities. It yields 4 sub-scores: work time missed due to pain (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With General Activity at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Score Pain Interference With General Activity at Week 64: Observed Data	Baseline, Week 64	BPI-sf is a self-administered questionnaire developed to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation. Severity of pain was measured based on questions 1 to 4. Question 5 (7-items) assessed level of pain interference on daily activities. Pain interference index was calculated as the mean of the seven BPI-sf pain interference items (question 5a to g), being pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Responses were given on an 11-point NRS with score ranging from 0 (does not interfere) to 10 (completely interferes), lower scores indicated less pain or pain interference.
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score	Baseline, Weeks 8, 16, 24, 40 and 56	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. Individual dimension scores ranged from 1.0 (least impairment of health state) to 5.0 (most impairment of health state). Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. 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.
Time to Discontinuation Due to Lack of Efficacy	Baseline up to Week 56	Time to discontinuation due to lack of efficacy was defined as the time interval from the date of first study drug administration up to the date of discontinuation of participant from treatment due to lack of efficacy.
Number of Days of Rescue Medication Used at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56	Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and 56	In case of inadequate pain relief, acetaminophen/paracetamol caplets, tablets, or capsules up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between day 1 and week 56. Number of days the participants used the rescue medication during the particular study weeks were summarized. As pre specified intent of study, for analyses after week 16 where multiple imputation was used, data was reported per 3 arms. This is because participants who received placebo from Day 1 and received tanezumab 5/10 mg at week 16, received placebo for the first 16 weeks, and their data before week 16 were not be imputed into analyses after week 16.
Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Low Back Pain From Baseline at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Mixed Baseline Observation Carried Forward (BOCF)/ Last Observation CF (LOCF)	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56	PGA of LBP assessed by asking question to participants:Considering all ways your low back pain affects you,how are you doing today? They responded on 5 point Likert scale ranging from 1-5, using IRT, where 1=very good (asymptomatic \& no limitation of normal activities);2=good (mild symptoms and no limitation of normal activities);3=fair (moderate symptoms and limitation of some normal activities);4=poor (severe symptoms \& inability to carry out most normal activities); \& 5=very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). Higher scores indicated worsening of condition. % of participants with improvement of at least 2 points from baseline in PGA of LBP were reported. Missing data was imputed using BOCF/LOCF. Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Health Care Resource Utilization (HCRU): Number of Visits of Services Received Directly Related to Low Back Pain	Baseline, Weeks 64 and 80	Low back pain HCRU assessed utilization of healthcare resources usage during last 3 months (for Baseline during the last 3 months for baseline, weeks 64 and 80, via IRT). Visits of services directly related to low back pain evaluated were: visits to primary care physician, neurologist, rheumatologist, physician assistant or nurse practitioner, pain specialist, orthopedist, physical therapist, chiropractor, alternative medicine or therapy, podiatrist, nutritionist/dietitian, radiologist, home healthcare services and other practitioner. Participants might have been counted more than once under various categories.
Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Low Back Pain	Baseline, Weeks 64 and 80	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of participants who were hospitalized due to low back pain.
Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Low Back Pain	Baseline, Weeks 64 and 80	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was duration since quitting job due to low back pain.
Treatment Satisfaction Score Determined With Treatment Satisfaction Questionnaire for Medication Version II (TSQM v II) at Weeks 16 and 56	Weeks 16 and 56	TSQM v.II: self-administered 11-item validated scale that quantified participant's level of satisfaction with study medication (7 questions scored on 7-point Likert scale \[1= extremely dissatisfied, 2=very dissatisfied, 3=dissatisfied, 4=somewhat satisfied, 5=satisfied, 6=very satisfied, 7=extremely satisfied\]), effectiveness and side effects/tolerability (3 questions scored on 5 point Likert scale \[1= extremely dissatisfied, 2=very dissatisfied, 3=somewhat dissatisfied, 4=slightly dissatisfied, 5=not at all dissatisfied\], 1 question on 2 point scale \[0 =No, 1=Yes\]). 11 questions of TSQM were used to calculate 4 endpoints of effectiveness, side effects, convenience and global satisfaction, each scored on a 0-100 scale with 100=best level of satisfaction. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to \& including W16 \& comparisons of tanezumab Vs tramadol for data up to \& including W56.
Number of Days of Rescue Medication Used at Week 64	Week 64	In case of inadequate pain relief, acetaminophen/paracetamol caplets, tablets, or capsules up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between day 1 and week 56. Number of days per week the participants used the rescue medication during the 4 weeks up to and including the particular study week were summarized.
Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving For Low Back Pain Before Enrolling?	Weeks 16 and 56	The mPRTI is a self-administered questionnaire containing participant reported treatment impact assessment (to assess participant satisfaction), participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. To assess previous treatment, participants responded for, 1=injectable prescription medicines, 2=prescription medicines taken by mouth, 3=surgery, 4=prescription medicines and surgery and 5=no treatment. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to \& including W16 \& comparisons of tanezumab Vs tramadol for data up to \& including W56.
Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline	Baseline up to Week 80	Primary Abnormality criteria: HGB, hematocrit, RBC count \<0.8\* lower limit of normal(LLN); Ery. mean corpuscular volume/hemoglobin/ HGB concentration, RBCs distribution width \<0.9\LLN, \>1.1\upper limit of normal(ULN); platelets \<0.5\LLN,\>1.75\ULN; WBC count\<0.6\LLN, \>1.5\ULN; Lymphocytes,Leukocytes,Neutrophils \<0.8\LLN, \>1.2\ULN; Basophils,Eosinophils,Monocytes\>1.2\ULN; Prothrombin time/Intl. normalized ratio\>1.1\ULN; total bilirubin\>1.5\ULN; aspartate aminotransferase,alanine aminotransferase,gamma GT,LDH,alkaline phosphatase \>3.0\ULN; total protein; albumin\<0.8\LLN, \>1.2\ULN; blood urea nitrogen,creatinine,Cholesterol,triglycerides \>1.3\ULN; Urate\>1.2\ULN; sodium\<0.95\LLN,\>1.05\ULN; potassium,chloride,calcium,magnesium,bicarbonate \<0.9\LLN, \>1.1\ULN; phosphate\<0.8\LLN, \>1.2\ULN; glucose\<0.6\LLN, \>1.5\ULN; HGB A1C \>1.3\ULN; creatine kinase\>2.0\ULN, specific gravity\<1.003, \>1.030; pH\<4.5, \>8; Urine Glucose, protein,HGB,bilirubin \>=1; Ketones\>=1;Urine erythrocytes,Leukocytes\>=20.
Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline	Baseline up to Week 80	Primary Abnormality criteria: hemoglobin; hematocrit; RBC count \< 0.8\LLN; Ery. mean corpuscular volume/ hemoglobin/ HGB concentration, erythrocytes distribution width \<0.9\LLN, \>1.1\ULN; platelets \<0.5\LLN,\>1.75\upper limit of normal (ULN); white blood cell count\<0.6\LLN, \>1.5\ULN; Lymphocytes, Leukocytes, Neutrophils \<0.8\LLN, \>1.2\ULN; Basophils, Eosinophils, Monocytes \>1.2\ULN; total bilirubin\>1.5\ULN; aspartate aminotransferase, alanine aminotransferase, gamma GT,LDH, alkaline phosphatase \>3.0\ULN; total protein; albumin\<0.8\LLN, \>1.2\ULN; blood urea nitrogen, creatinine, Cholesterol, triglycerides \>1.3\ULN; Urate \>1.2\ULN; sodium \<0.95\LLN,\>1.05\ULN; potassium, chloride, calcium, magnesium, bicarbonate \<0.9\LLN, \>1.1\ULN; phosphate \<0.8\LLN, \>1.2\ULN; glucose \<0.6\LLN, \>1.5\ULN; Hemoglobin A1C \>1.3\ULN; creatine kinase \>2.0\ULN; Nitrite \>=1.
Change From Screening in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80	Screening (up to maximum of 37 days prior to Baseline), Weeks 24, 56 and 80	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. Pre-specified intent of study for safety summaries until W80 was to summarize data by 4 arms.
Amount of Rescue Medication Used at Weeks 2, 4, 8, 12 and 16	Weeks 2, 4, 8, 12 and 16	In case of inadequate pain relief, acetaminophen/paracetamol caplets, tablets, or capsules up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between day 1 and week 56. The total dosage of acetaminophen in milligrams used during the specified week were summarized. Pre-specified intent of study for efficacy data up to W16 was to analyze participants who received placebo from Day1 and then received tanezumab 5/10 mg at W16,together,in placebo arm.Data has been reported per four arms.
Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Low Back Pain	Baseline, Weeks 64 and 80	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of visits to the emergency room due to low back pain.
Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Low Back Pain	Baseline, Weeks 64 and 80	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of participants who quit job due to low back pain.
Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80	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. Pre-specified intent of study for safety summaries until W80 was to summarize data by 4 arms.
Number of Participants With Anti Tanezumab Antibodies	Baseline, Weeks 8, 16, 32, 40, 48, 56, 64 and 80	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. Pre-specified intent of study for safety summaries until W80 was to summarize data by 4 arms.
Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- Overall, do You Prefer The Drug That You Received in This Study to Previous Treatment?	Weeks 16 and 56	mPRTI : self-administered questionnaire containing participant reported treatment impact assessment (to assess participant satisfaction),participant global preference assessment (to assess previous treatment \& preference to continue using investigational product) \& participant willingness to use drug again assessment. To assess preference to continue using investigational product, participants responded using IRT on 5 point likert scale from 1-5, where, 1= yes, I definitely prefer drug that I am receiving now, 2= I have a slight preference for drug that I am receiving now, 3= I have no preference either way, 4= I have a slight preference for my previous treatment, 5= No, I definitely prefer my previous treatment. Higher scores indicate lesser preference to use investigational product. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to \& including W16 \& comparisons of tanezumab Vs tramadol for data up to \& including W56.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to Week 80	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to week 80 that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.
Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Week 56	Baseline up to Week 56	Treatment-related AE was any untoward medical occurrence attributed to study drug in participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to W56 that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator. Pre-specified intent of study for summaries for the entire treatment period (up to week 56), data was summarized by 3 arms.
Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80	Heart rate was measured at sitting position. Pre-specified intent of study for safety summaries until W80 was to summarize data by 4 arms.
Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Low Back Pain	Baseline, Weeks 64 and 80	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of participants who visited the emergency room due to low back pain.
Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Low Back Pain	Baseline, Weeks 64 and 80	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of nights stayed in the hospital due to low back pain.
Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things	Baseline, Weeks 64 and 80	Low back pain HCRU assessed utilization of healthcare resources during the last 3 months for baseline, weeks 64 and 80, via IRT. Domain evaluated was number of participants who used any aids/devices for doing things. Aids such as walking aid, wheelchair, device or utensil for dress/bathe/eat and any other aids/devices.
Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Willingness to Use Drug Again Assessment- Willing to Use The Same Drug That You Have Received in This Study For Your Low Back Pain Pain?	Weeks 16 and 56	mPRTI: self-administered questionnaire containing participant reported treatment impact assessment (to assess participant satisfaction),participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) \& participant willingness to use drug again assessment. To assess participants willingness to use drug again, participants responded using IRT on 5 point likert scale from 1-5, where, 1= yes, I would definitely want to use the same drug again, 2= I might want to use the same drug again, 3= I am not sure, 4= I might not want to use the same drug again, 5= no, I definitely would not want to use the same drug again. Higher scores indicate lesser willingness to use the investigational product. Pre-specified intent of study was to compare tanezumab Vs placebo for data up to \& including W16 \& comparisons of tanezumab Vs tramadol for data up to \& including W56.
Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80	Measurement of BP included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP). Pre-specified intent of study for safety summaries until W80 was to summarize data by 4 arms.
Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16, 56 and 80	Baseline, Weeks 16, 56 and 80	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 {RR interval, PR interval, QRS interval, QT interval, QT interval corrected using Bazett's formula (QTcB) and QT interval corrected using Fridericia's formula (QTcF)} were collected. Pre-specified intent of study for safety summaries until W80 was to summarize data by 4 arms.
Percentage of Participants With Adjudicated Joint Safety Outcomes	Baseline up to Week 80	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.
Percentage of Participants With Total Joint Replacements	Baseline up to Week 80	Percentage of participants who underwent at least one total knee, hip or shoulder joint replacement surgery.
Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 16, 56 and 80	Baseline, Weeks 16, 56 and 80	Heart rate was measured at sitting position. Pre-specified intent of study for safety summaries until W80 was to summarize data by 4 arms.
Number of Participants With Confirmed Orthostatic Hypotension	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80	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. Pre-specified intent of study for safety summaries until W80 was to summarize data by 4 arms. Data not collected after W16 in placebo arm for this OM, as those who met criteria to continue, switched to active treatment with tanezumab after W16.

Trial Locations

Locations (255): Northwestern University
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Chicago, Illinois, United States
Chicago Anesthesia Pain Specialists
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Chicago, Illinois, United States
Neuro-Pain Medical Center
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Fresno, California, United States
Collaborative Neuroscience Network, LLC.
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Long Beach, California, United States
University of Southern California
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Los Angeles, California, United States
Diablo Clinical Research, Inc.
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Walnut Creek, California, United States
Clinical Research of South Florida
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Coral Gables, Florida, United States
Avail Clinical Research,LLC
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DeLand, Florida, United States
Clinical Neuroscience Solutions, Inc.
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Jacksonville, Florida, United States
Sensible Healthcare, LLC.
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Ocoee, Florida, United States
Progressive Medical Research
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Port Orange, Florida, United States
Georgia Institute for Clinical Research, LLC
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Marietta, Georgia, United States
Non-Surgical Orthopaedics, P.C.
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Marietta, Georgia, United States
Better Health Clinical Research Inc
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Newnan, Georgia, United States
Better Health Clinical Research, Inc.
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Newnan, Georgia, United States
North Georgia Internal Medicine
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Woodstock, Georgia, United States
Medex Healthcare Research Inc
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Chicago, Illinois, United States
Chicago Clinical Research Institute, Inc.
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Chicago, Illinois, United States
Northwestern University, Feinberg School of Medicine, Lavin Pavilion
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Chicago, Illinois, United States
Clinical Investigation Specialists, Inc.
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Skokie, Illinois, United States
Lafayette Clinical Research Group
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Lafayette, Indiana, United States
St Elizabeth Hospital Edgewood
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Edgewood, Kentucky, United States
Olive Branch Family Medical Center
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Olive Branch, Mississippi, United States
Healthwise Medical Associates
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Brooklyn, New York, United States
AAIR Research Center
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Rochester, New York, United States
On Site Clinical Solutions, LLC
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Mooresville, North Carolina, United States
Wake Research Associates, LLC
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Raleigh, North Carolina, United States
Lillestol Research, LLC
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Fargo, North Dakota, United States
Clinical Inquest Center Ltd
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Beavercreek, Ohio, United States
Heartland Diagnostics
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Frgi, North Dakota, United States
Prestige Clinical Research
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Franklin, Ohio, United States
Great Lakes Medical Research, LLC
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Mentor, Ohio, United States
Oaktree Clinic
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Mentor, Ohio, United States
Bone Joint & Spine Surgeons, Inc.
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Toledo, Ohio, United States
Brandywine Clinical Research
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Downingtown, Pennsylvania, United States
Altoona Center for Clinical Research
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Duncansville, Pennsylvania, United States
Omega Medical Research
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Warwick, Rhode Island, United States
TLM Medical Services
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Columbia, South Carolina, United States
DeGarmo Institute of Medical Research
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Greer, South Carolina, United States
Health Concepts
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Rapid City, South Dakota, United States
PCET Research Center, LLC
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Knoxville, Tennessee, United States
KRK Medical Research
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Arlington, Texas, United States
The Pain Relief Center
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Plano, Texas, United States
Physicians Research Options, LLC
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Draper, Utah, United States
Charlottesville Medical Research Center, LLC
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Charlottesville, Virginia, United States
Virginia Research Center
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Midlothian, Virginia, United States
National Clinical Research - Richmond, Inc.
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Richmond, Virginia, United States
Northwest Clinical Research Center
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Bellevue, Washington, United States
London Road Diagnostic Clinic & Medical Centre
🇨🇦
Sarnia, Ontario, Canada
SKDS Research Inc.
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Newmarket, Ontario, Canada
Fukuoka Mirai Hospital
🇯🇵
Higashi-ku,Fukuoka, Fukuoka, Japan
Hakodate Ohmura Orthopedic Hospital
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Hakodate, Hokkaido, Japan
Seoul National University Hospital
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Seoul, Korea, Republic of
Samsung Medical Center
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Seoul, Korea, Republic of
Advances In Health
🇺🇸
Houston, Texas, United States
Centex Studies, Inc./Clear Lake Family Physicians
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Houston, Texas, United States
Affiliated Clinical Research, Inc.
🇺🇸
Las Vegas, Nevada, United States
Office of Stephen H. Miller, MD
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Las Vegas, Nevada, United States
Quality Research & Medical Center LLC
🇺🇸
Miami, Florida, United States
Columbus Clinical Services, LLC
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Miami, Florida, United States
Larkin Imaging Center
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Miami, Florida, United States
M & M Medical Center, Inc
🇺🇸
Miami, Florida, United States
Hightop Medical Research Center
🇺🇸
Cincinnati, Ohio, United States
New Horizons Clinical Research
🇺🇸
Cincinnati, Ohio, United States
Bekes Megyei Koezponti Korhaz Dr Rethy Pal Tagkorhaz
🇭🇺
Bekescsaba, Hungary
Clinexpert Egeszsegugyi Szolgaltato es Kereskedelmi Kft.
🇭🇺
Budapest, Hungary
Obudai Egeszsegugyi Centrum Ktf.
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Budapest, Hungary
Kohno Clinical Medicine Research Institute Daisan Kitashinagawa Hospital
🇯🇵
Shinagawa-ku, Tokyo, Japan
The Pain Center of Arizona
🇺🇸
Phoenix, Arizona, United States
Arizona Research Center
🇺🇸
Phoenix, Arizona, United States
COR Clinical Research, L.L.C
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Oklahoma City, Oklahoma, United States
Health Research of Oklahoma
🇺🇸
Oklahoma City, Oklahoma, United States
NPC Research
🇺🇸
Oklahoma City, Oklahoma, United States
Lynn Health Science Institute
🇺🇸
Oklahoma City, Oklahoma, United States
Quality Medical Research
🇺🇸
Nashville, Tennessee, United States
Quality Research, Inc.
🇺🇸
San Antonio, Texas, United States
Lee Medical Associates, PA
🇺🇸
San Antonio, Texas, United States
Progressive Clinical Research, PA
🇺🇸
San Antonio, Texas, United States
Central Alabama Research
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Birmingham, Alabama, United States
Brigham and Women's Hospital
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Chestnut Hill, Massachusetts, United States
Heartland Clinical Research, Inc.
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Omaha, Nebraska, United States
Meridien Research
🇺🇸
Tampa, Florida, United States
CRU Hungary Ltd., MISEK-Radiology Department
🇭🇺
Miskolc, Hungary
Specialist, S.L.
🇪🇸
Barcelona, Spain
Lynn Institute of the Ozarks
🇺🇸
Little Rock, Arkansas, United States
George Stanley Walker, MD
🇺🇸
New Orleans, Louisiana, United States
Centex Studies, Inc
🇺🇸
Lake Charles, Louisiana, United States
Mayfield Imaging Center
🇺🇸
Crestview Hills, Kentucky, United States
Columbus Regional Research Institute
🇺🇸
Columbus, Georgia, United States
Southeast Regional Research Group
🇺🇸
Savannah, Georgia, United States
Center for Advanced Research & Education
🇺🇸
Gainesville, Georgia, United States
S&W Clinical Research
🇺🇸
Fort Lauderdale, Florida, United States
Northwestern Memorial Hospital - Arkes Pavilion, Diagnostic Testing Center
🇺🇸
Chicago, Illinois, United States
Northwestern University Feinberg School of Medicine
🇺🇸
Chicago, Illinois, United States
Cahaba Research
🇺🇸
Birmingham, Alabama, United States
Alabama Clinical Research, LLC
🇺🇸
Mobile, Alabama, United States
Alabama Orthopaedic Clinic, P.C.
🇺🇸
Mobile, Alabama, United States
Coastal Clinical Research
🇺🇸
Mobile, Alabama, United States
Horizon Research Partners, LLC
🇺🇸
Mobile, Alabama, United States
The Center for Clinical Trials, Inc.
🇺🇸
Saraland, Alabama, United States
Valley Pain Consultants
🇺🇸
Scottsdale, Arizona, United States
KLR Business Group dba Arkansas Clinical Research
🇺🇸
Little Rock, Arkansas, United States
Anaheim Clinical Trials, LLC
🇺🇸
Anaheim, California, United States
eStudySite
🇺🇸
La Mesa, California, United States
USC IDS Pharmacy
🇺🇸
Los Angeles, California, United States
Valley Research-Trials
🇺🇸
Fresno, California, United States
Providence Clinical Research
🇺🇸
North Hollywood, California, United States
Artemis Institute for Clinical Research
🇺🇸
San Diego, California, United States
Elite Clinical Trials, Inc.
🇺🇸
Wildomar, California, United States
Bayview Research Group
🇺🇸
Valley Village, California, United States
Alpine Clinical Research Center
🇺🇸
Boulder, Colorado, United States
Mountain View Clinical Research, Inc
🇺🇸
Denver, Colorado, United States
New England Research Associates, LLC
🇺🇸
Bridgeport, Connecticut, United States
My Health 1st Urgent Care
🇺🇸
Milford, Connecticut, United States
Stamford Therapeutics Consortium
🇺🇸
Stamford, Connecticut, United States
Orthopedic Research Institute
🇺🇸
Boynton Beach, Florida, United States
JEM Research Institute
🇺🇸
Atlantis, Florida, United States
Midland Florida Clinical Research Center, LLC
🇺🇸
DeLand, Florida, United States
Pines Clinical Research Inc.
🇺🇸
Hollywood, Florida, United States
MD Clinical
🇺🇸
Hallandale Beach, Florida, United States
Crystal Biomedical Research, LLC
🇺🇸
Miami Lakes, Florida, United States
Health Awareness, Inc.
🇺🇸
Jupiter, Florida, United States
Gulfcoast Research Institute
🇺🇸
Sarasota, Florida, United States
Drug Studies America
🇺🇸
Marietta, Georgia, United States
Palm Beach Research Center
🇺🇸
West Palm Beach, Florida, United States
River Birch Research Alliance, LLC
🇺🇸
Blue Ridge, Georgia, United States
East-West Medical Research Institute
🇺🇸
Honolulu, Hawaii, United States
North Georgia Clinical Research
🇺🇸
Woodstock, Georgia, United States
Great Lakes Clinical Trials
🇺🇸
Chicago, Illinois, United States
The Iowa Clinic Medical Imaging
🇺🇸
West Des Moines, Iowa, United States
Investigators Research Group, LLC
🇺🇸
Brownsburg, Indiana, United States
Lafayette Regional Vein and Laser Center
🇺🇸
Lafayette, Indiana, United States
The Iowa Clinic - Internal Medicine
🇺🇸
Des Moines, Iowa, United States
The Iowa Clinic
🇺🇸
West Des Moines, Iowa, United States
MediSphere Medical Research Center, LLC
🇺🇸
Evansville, Indiana, United States
Mid-America Physiatrists, P.A.
🇺🇸
Overland Park, Kansas, United States
Professional Research Network of Kansas, LLC
🇺🇸
Wichita, Kansas, United States
Otri-Med Corporation
🇺🇸
Edgewood, Kentucky, United States
Willis-Knighton Physician Network/WKB Family Medicine Associates
🇺🇸
Bossier City, Louisiana, United States
Willis-Knighton Physician Network/ Spine and Pain Specialist
🇺🇸
Bossier City, Louisiana, United States
Klein & Associates, M.D., P.A.
🇺🇸
Cumberland, Maryland, United States
Best Clinical Trials, LLC
🇺🇸
New Orleans, Louisiana, United States
The Center for Rheumatology and Bone Research
🇺🇸
Wheaton, Maryland, United States
Great Lakes Research Group, Inc.
🇺🇸
Bay City, Michigan, United States
Oakland Medical Research
🇺🇸
Troy, Michigan, United States
Michigan Orthopaedic Spine Surgeons
🇺🇸
Rochester Hills, Michigan, United States
Michigan Pain Consultants
🇺🇸
Wyoming, Michigan, United States
Physician's Surgery Center
🇺🇸
Jackson, Mississippi, United States
Medex Healthcare Research, Inc.
🇺🇸
Saint Louis, Missouri, United States
Office of Robert Kaplan, DO
🇺🇸
Las Vegas, Nevada, United States
CRI Worldwide, LLC
🇺🇸
Marlton, New Jersey, United States
Comprehensive Clinical Research
🇺🇸
Berlin, New Jersey, United States
Advanced Biomedical Research of America
🇺🇸
Las Vegas, Nevada, United States
Premier Research
🇺🇸
Trenton, New Jersey, United States
University Clinical Research Center
🇺🇸
Somerset, New Jersey, United States
Albuquerque Clinical Trials, Inc.
🇺🇸
Albuquerque, New Mexico, United States
New Mexico Clinical Research & Osteoporosis Center, Inc.
🇺🇸
Albuquerque, New Mexico, United States
University of Rochester
🇺🇸
Rochester, New York, United States
The Medical Research Network, LLC
🇺🇸
New York, New York, United States
Drug Trials America
🇺🇸
Hartsdale, New York, United States
Northstate Clinical Research
🇺🇸
Lenoir, North Carolina, United States
Plains Clinical Research Center, LLC
🇺🇸
Fargo, North Dakota, United States
Optimed Research LTD
🇺🇸
Columbus, Ohio, United States
Valley Medical Research/Valley Medical Primary Care
🇺🇸
Centerville, Ohio, United States
Clinical Trial Network
🇺🇸
Houston, Texas, United States
Diex Research Sherbrooke Inc.
🇨🇦
Sherbrooke, Quebec, Canada
A2 reumatologi og idraesmedicin ApS
🇩🇰
Hillerod, Denmark
G.R.M.O. (Groupe de recherche en maladies osseuses) Inc.
🇨🇦
Quebec, Canada
Centre de recherche Saint-Louis
🇨🇦
Quebec, Canada
Hopital Cochin
🇫🇷
Paris Cedex 14, France
CRU Hungary Ltd., MISEK HOSPITAL
🇭🇺
Miskolc, Hungary
Jutrix Kft.
🇭🇺
Kecskemét, Hungary
Tolna Megyei Balassa Janos Korhaz, Ortopediai osztaly
🇭🇺
Szekszard, Hungary
Clinfan Kft.
🇭🇺
Szekszard, Hungary
Aichi Medical University Hospital
🇯🇵
Nagakute, Aichi, Japan
Nagoya University Hospital
🇯🇵
Showa-ku, Nagoya, Aichi, Japan
Kyushu Rosai Hospital
🇯🇵
Kokuraminami-ku,Kitakyushu, Fukuoka, Japan
Chiba Central Medical Center
🇯🇵
Wakaba-ku, Chiba, Chiba, Japan
Chiba University Hospital
🇯🇵
Chuo-ku, Chiba, Chiba, Japan
Fukushima Medical University Aizu Medical Center
🇯🇵
Aizuwakamatsu, Fukushima, Japan
Funabashi Municipal Medical Center
🇯🇵
Funabashi, Chiba, Japan
Chiba Rosai Hospital
🇯🇵
Ichihara, Chiba, Japan
Takagi Hospital
🇯🇵
Okawa, Fukuoka, Japan
Hakodate Central General Hospital
🇯🇵
Hakodate, Hokkaido, Japan
Medical corporate corporation hoshikai Onishi medical clinic
🇯🇵
Kako-gun, Hyogo, Japan
Kobe Konan Yamate Clinic
🇯🇵
Higashinada-ku, Kobe, Hyogo, Japan
Marunouchi Hospital
🇯🇵
Matsumoto, Nagano, Japan
Kobe Red Cross Hospital
🇯🇵
Kobe, Hyogo, Japan
Omuro Orthopedic Clinic
🇯🇵
Himeji, Hyogo, Japan
Morita Hospital
🇯🇵
Komatsu, Ishikawa, Japan
National Hospital Organization Beppu Medical Center
🇯🇵
Beppu, Oita, Japan
National Hospital Organization Kanazawa Medical Center
🇯🇵
Kanazawa, Ishikawa, Japan
Rinku General Medical Center
🇯🇵
Izumisano, Osaka, Japan
Sobajima Clinic
🇯🇵
Higashiosaka, Osaka, Japan
Minamiosaka Hospital
🇯🇵
Suminoe-ku, Osaka, Osaka, Japan
Saitama Jikei Hospital
🇯🇵
Kumagaya, Saitama, Japan
Tokyo Medical and Dental University Medical Hospital
🇯🇵
Bunkyo-ku, Tokyo, Japan
Hamamatsu University School of Medicine, University Hospital
🇯🇵
Hamamatsu, Shizuoka, Japan
Fussa Hospital
🇯🇵
Fussa, Tokyo, Japan
Tokyo Saiseikai Central Hospital
🇯🇵
Minato-ku, Tokyo, Japan
Keio University Hospital
🇯🇵
Shinjuku-ku, Tokyo, Japan
Yonezawa City Hospital
🇯🇵
Yonezawa, Yamagata, Japan
Ohimachi Orthopaedic Clinic
🇯🇵
Shinagawa-ku, Tokyo, Japan
Yamaguchi University Hospital
🇯🇵
Ube, Yamaguchi, Japan
Shimonoseki City Hospital
🇯🇵
Shimonoseki-shi, Yamaguchi, Japan
Chihaya Hospital
🇯🇵
Fukuoka, Japan
Fukushima Medical University Hospital
🇯🇵
Fukushima, Japan
Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
🇯🇵
Hiroshima, Japan
Kuroda Orthopedic Hospital
🇯🇵
Fukuoka, Japan
CTC Pharmacy, Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Toyama University Hospital
🇯🇵
Toyama, Japan
Clinical Trial Pharmacy, Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Hospital Nuestra Senora de la Esperanza
🇪🇸
Santiago de Compostela, A Coruna, Spain
Severance Hospital
🇰🇷
Seoul, Korea, Republic of
CTC Pharmacy, Severance Hospital
🇰🇷
Seoul, Korea, Republic of
Complejo Hospitalario Universitario A Coruña
🇪🇸
A Coruna, Spain
Complejo Hospitalario Universitario A Coruna. Servicio de Farmacia
🇪🇸
A Coruna, Spain
Instituto de Ciencias Medicas
🇪🇸
Alicante, Spain
Hospital de Mar Servicio de Radiologia
🇪🇸
Barcelona, Spain
Hospital del Mar Servicio de Farmacia
🇪🇸
Barcelona, Spain
Specialist. Farmacia
🇪🇸
Barcelona, Spain
Hospital Universitario Quiron-Dexeus
🇪🇸
Barcelona, Spain
Hospital Sanitas CIMA
🇪🇸
Barcelona, Spain
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Hospital Universitario Quiron-Dexeus. Servicio de Farmacia
🇪🇸
Barcelona, Spain
Hospital del Mar
🇪🇸
Barcelona, Spain
Hospital Universitario La Paz.
🇪🇸
Madrid, Spain
Hospital La Moraleja
🇪🇸
Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸
Malaga, Spain
Hospital La Moraleja. Pharmacy Service
🇪🇸
Madrid, Spain
CTC (Clinical Trial Center) Sahlgrenska University Hospital
🇸🇪
Gothenburg, Sweden
Pharmasite
🇸🇪
Malmo, Sweden
Hospital Regional Universitario del Malaga
🇪🇸
Malaga, Spain
ProbarE i Stockholm AB
🇸🇪
Stockholm, Sweden
Core Healthcare Group
🇺🇸
Cerritos, California, United States
Triwest Research Associates, LLC
🇺🇸
El Cajon, California, United States
Catalina Research Institute, LLC
🇺🇸
Montclair, California, United States
Research Center of Fresno, Inc.
🇺🇸
Fresno, California, United States
Beacon Clinical Research, LLC
🇺🇸
Quincy, Massachusetts, United States
CRC of Jackson, LLC
🇺🇸
Jackson, Mississippi, United States
Mountain View Clinical Research, Inc.
🇺🇸
Denver, Colorado, United States
Encompass Clinical Research
🇺🇸
Spring Valley, California, United States
Buynak Clinical Research, P.C.
🇺🇸
Valparaiso, Indiana, United States
ActivMed Practices & Research, Inc.
🇺🇸
Portsmouth, New Hampshire, United States
National Pain Research Institute
🇺🇸
Orlando, Florida, United States
Ferguson Family Medicine
🇺🇸
Mesa, Arizona, United States
MedVadis Research Corporation
🇺🇸
Watertown, Massachusetts, United States
Lowcountry Orthopaedics & Sports Medicine
🇺🇸
North Charleston, South Carolina, United States
Saitama Municipal Hospital
🇯🇵
Saitama, Japan
PMG Research of Winston-Salem, LLC
🇺🇸
Winston-Salem, North Carolina, United States
Northern California Research
🇺🇸
Sacramento, California, United States
Compass Research, LLC
🇺🇸
Orlando, Florida, United States
The Center for Clinical Research
🇺🇸
Winston-Salem, North Carolina, United States
Primary Care of Arkansas, P.A.
🇺🇸
Little Rock, Arkansas, United States
Washington Center for Pain Management
🇺🇸
Bellevue, Washington, United States