Change From Baseline in Roland Morris Disability Questionnaire (RMDQ) at Week 16 for Tanezumab Versus (Vs) Placebo
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 Average Low Back Pain Intensity (LBPI) Score for Tanezumab Versus (Vs) Tramadol at 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
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.
Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at 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
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
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
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.
Change From Baseline in Patient's Global Assessment (PGA) of Low Back Pain at Week 64: Observed Data
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 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)
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.
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)
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.
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)
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
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 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 Worst Pain at Week 64: Observed Data
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 Brief Pain Inventory-Short Form (BPI-sf) Scores Average Pain at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
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 Average Pain at Week 64: Observed Data
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 Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
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 Index at Week 64: Observed Data
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 General Activity at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
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
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 Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
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 Walking Ability at Week 64: Observed Data
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 Sleep at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56: Observed Data
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
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
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
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
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.
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)
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.
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Dimensions Score
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.
European Quality of Life- 5 Dimension-5 Levels (EQ-5D-5L) Overall Health Utility Score/ Index Value
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
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
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.
Number of Participants Who Withdrew Due to Lack of Efficacy
Number of participants who withdrew from treatment due to lack of efficacy have been reported here.
Time to Discontinuation Due to Lack of Efficacy
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 Participants Who Took Rescue Medication During 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.
Number of Participants Who Took Rescue Medication During Week 64: Observed Data
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.
Number of Days of Rescue Medication Used at 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.
Number of Days of Rescue Medication Used at 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.
Amount of Rescue Medication Used at 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 of Services Received Directly Related to Low Back Pain
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 Who Visited the Emergency Room Due to Low Back Pain
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 Visits to the Emergency Room Due to Low Back Pain
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 Hospitalized Due to Low Back Pain
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): Number of Nights Stayed in the Hospital Due to Low Back Pain
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
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.
Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Low Back Pain
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.
Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Low Back Pain
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
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.
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?
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.
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?
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.
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?
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.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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
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.
Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline
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
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 Baseline in Blood Pressure (BP) at 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 Heart Rate at 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.
Change From Baseline in Electrocardiogram (ECG) Parameters at 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.
Change From Baseline in Heart Rate (as Assessed by ECG) at 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
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.
Change From Screening in Survey of Autonomic Symptom (SAS) Scores at 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.
Percentage of Participants With Adjudicated Joint Safety Outcomes
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
Percentage of participants who underwent at least one total knee, hip or shoulder joint replacement surgery.
Change From Baseline in Neuropathy Impairment Score (NIS) at 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
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.