Long Term Safety and Efficacy Study of Tanezumab in Japanese Adult Subjects With Chronic Low Back Pain

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 24 weeks after last dose of study drug (up to Week 80) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.

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 24 weeks after last dose of study drug (up to Week 80). Relatedness to study drug was assessed by the investigator. AEs included both serious and non-serious AEs.

Abnormality criteria included: hemoglobin (HGB); hematocrit; erythrocytes < 0.8*lower limit of normal (LLN); erythrocyte mean corpuscular volume/HGB/ HGB concentration, erythrocytes distribution width <0.9*LLN, >1.1*upper limit of normal (ULN); platelets <0.5*LLN,>1.75* ULN; 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 (AT), alanine AT, gamma glutamyl transferase, lactate dehydrogenase, 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; nitrite >=1. Investigator judged clinical significance of laboratory test abnormalities.

Vital signs included systolic blood pressure, diastolic blood pressure and pulse rate. Investigator judged clinical significance of vital signs' abnormalities.

Orthostatic hypotension was defined as postural change (supine to standing) that met the following criteria: for systolic blood pressure (BP) less than or equal to (<=) 150 millimeter of mercury (mmHg) (mean supine): reduction in systolic BP >=20 mmHg or reduction in diastolic BP >=10 mmHg at the 1 and/or 3 minute standing BP measurements. For systolic BP greater than (>) 150 mmHg (mean supine): reduction in systolic BP >=30 mmHg or reduction in diastolic BP >=15 mmHg at the 1 and/or 3 minute standing BP measurements. If the 1 minute or 3 minute standing BP in a sequence met the orthostatic hypotension criteria, then that sequence was considered positive. If 2 of 2 or 2 of 3 sequences were positive, then orthostatic hypotension was considered confirmed.

SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

SAS is a participant rated 12 items questionnaire for males and 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during the past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants were asked to answer "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If a participant answered "Yes" for a symptom, then impact of that symptom was rated on a 5 point scale, ranged from 1 (least sever impact) to 5 (most severe impact), where higher scores signified more severe impact of symptoms. The total symptom impact score was calculated as the sum of impact of all symptoms. Overall possible range for the total symptom impact score was 0 (no impact) to 60 (extreme impact) for males and 0 (no impact) to 55 (extreme impact) for females, higher scores indicated more severe impact of symptoms on participants' well-being.

SAS: participant rated 12 items questionnaire for males; 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants answered "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If participant answered "Yes" for a symptom, then impact of that symptom was rated on 5 point scale (1 [least sever impact] to 5 [most severe impact]); higher scores = more severe impact of symptoms. Total impact score = sum of impact of all symptoms; range for males =0 (no impact) to 60 (extreme impact); females =0 (no impact) to 55 (extreme impact); higher scores = more severe impact of symptoms on participants' well-being. Participants discontinuing from study treatment before Week 56, had early termination follow-up visit 1 at 8 weeks after last dose of tanezumab or placebo matched to tanezumab.

SAS: participant rated 12 items questionnaire for males; 11 items questionnaire for females. SAS measures autonomic symptoms of neuropathy and their impact on participants' well-being, during past 6 months. Each item was related to a symptom/health problem. At scheduled time points, participants answered "Yes" or "No" for each of symptoms/health problems experienced during past 6 months. If participant answered "Yes" for a symptom, then impact of that symptom was rated on 5 point scale (1 [least sever impact] to 5 [most severe impact]); higher scores = more severe impact of symptoms. Total impact score = sum of impact of all symptoms; range for males =0 (no impact) to 60 (extreme impact); females =0 (no impact) to 55 (extreme impact); higher scores = more severe impact of symptoms on participants' well-being. Participants discontinuing from study treatment before Week 56, had early termination follow-up visit 3 at 24 weeks after last dose of tanezumab or placebo matched to tanezumab.

Electrocardiogram assessment included PR, QRS, QT, QT interval corrected using Fridericia's formula (QTcF), QT interval corrected using Bazett's formula (QTcB), RR intervals, and heart rate. Investigator judged clinical significance of electrocardiogram assessment.

Percentage of participants with individual joint safety adjudication outcomes: rapidly progressive osteoarthritis (OA) type-1 only, rapidly progressive OA type-2 only, primary osteonecrosis, pathological fracture and subchondral insufficiency fracture is reported. Rapidly progressive (RP) OA type 1 events were those that the adjudication committee considered to have significant loss of joint space width >= 2 millimeter within approximately 1 year without gross structural failure. RP OA type 2 events were those considered to have destruction of bone including limited or total collapse of at least 1 subchondral surface that is not normally present in conventional end-stage osteoarthritis. Subchondral insufficiency fractures are a type of stress fractures which occur below the cartilage on the weight bearing surface of a bone.

Individual adjudicated joint safety outcomes/event: rapidly progressive OA (type-1,type-2), primary osteonecrosis, pathological fracture and subchondral insufficiency fracture. Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Event rate for any individual adjudicated joint safety outcome/event = the number of events per 1000 participant-years at risk.

Percentage of participants with at least 1 total knee, total hip or total shoulder joint replacement were reported.

Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant had no TJR, or (ii) date of TJR (earliest TJR within each participant in the case of multiple TJRs). Event rate = number of events per 1000 participant-years at risk.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits.

NIS is a standardized instrument used to evaluate signs of peripheral neuropathy in participants. NIS is the sum of scores of 37 items, from both the left and right side of following 4 domains: cranial nerves (5 items), muscle weakness (19 items), reflexes (5 items) and sensation (8 items). Each of 24 items related to cranial nerves and muscle weakness, scored from 0 (normal) to 4 (paralysis); higher scores indicated higher abnormality/impairment. Each of 13 items related to reflexes and sensation, scored as 0 (normal), 1 (decreased) and 2 (absent); higher scores indicated lesser reflexes and sensation. For NIS possible overall score (combined of both left and right sides of each domain), ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased/more neuropathic deficits. Largest change from baseline here means worst post- baseline change value (among all change from baseline values).

Human serum samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a validated analytical method. Number of participants with presence of anti-tanezumab antibodies are reported.

Physical examination included assessment of general appearance, skin, head, neck, eyes, ears, nose, throat, abdomen, lungs, heart, thyroid, and extremities. Investigator judged abnormality in physical examinations. Only those rows have been reported which had at least 1 participant with abnormality data in any of the reporting arms.

Average LBPI was assessed on an 11-point numeric rating scale (NRS). Participants described their average LBPI during the past 24 hours (at each specified/scheduled time-point) on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated worse pain.

Average LBPI was assessed on an 11-point NRS. Participants described their average LBPI during the past 24 hours (at each specified/scheduled time-point) on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated worse pain.

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. Participants were asked to check/select only those items out of 24 items, which described them at each specified time point. The total number of items checked in questionnaire was equal to RMDQ total score, overall possible score ranging from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater/more disability.

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. Participants were asked to check/select only those items out of 24 items, which described them at each specified time point. The total number of items checked in questionnaire was equal to RMDQ total score, overall possible score ranging from 0 (no disability) to 24 (maximum disability), where higher scores indicated greater/more disability.

PGA of low back pain 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 to 5, using interactive response technology (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.

Average LBPI was assessed on an 11-point numeric rating scale (NRS). Participants described their average LBPI during the past 24 hours (at each specified/scheduled time point) on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated worse pain. Percentage of participants with cumulative reduction (as percent change) (greater than [>] 0%; >= 10, 20, 30, 40, 50, 60, 70, 80, 90 and equals to [=] 100%) in average LBPI from baseline to weeks 16, 24 and 56 were reported. Participants (%) might have been counted more than once under various rows.

Average LBPI was assessed on an 11-point numeric rating scale (NRS). Participants described their average LBPI during the past 24 hours (at each specified/scheduled time point) on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated worse pain. Percentage of participants with reduction in average LBPI of at least (>=) 30%, 50%, 70% and 90% at Weeks 16, 24, 40, and 56 compared to baseline are reported here. Participants (%) might have been counted more than once under various rows.

BPI-sf is a self-administered questionnaire to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation at specified time points. BPI-sf scores for worst pain: participants were asked to rate their pain by circling any 1 number from 0 (no pain) to 10 (pain as bad as you can imagine) that best describes their pain at its worst in the last 24 hours; higher scores indicated worse pain.

BPI-sf is a self-administered questionnaire to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation at specified/scheduled time points. BPI-sf scores for average pain: participants were asked to rate their pain by circling any 1 number from 0 (no pain) to 10 (pain as bad as you can imagine) that best describes their pain on average in the last 24 hours; higher scores indicated worse pain.

BPI-sf is a self-administered questionnaire to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation at specified/scheduled time points. Pain interference index was calculated as the mean of the 7 BPI-sf pain interference items: pain interference with general activity; mood; walking ability; normal work (outside home and housework); relations with other people; sleep and enjoyment of life. Each of the 7 items had score range from 0 (does not interfere) to 10 (completely interferes), higher scores indicated more interference in daily activities due to pain. Overall score range for pain interference index was 0 (no interference) to 10 (complete interference), higher score = higher interference.

BPI-sf is a self-administered questionnaire to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation at specified/scheduled time points. BPI-sf scores for pain interference with general activity: participants were asked to circle from any 1 number from 0 (no interference) to 10 (complete interference) that described how, during the past 24 hours, pain has interfered with their general activity; higher scores indicated higher interference.

BPI-sf is a self-administered questionnaire to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation at specified/scheduled time points. BPI-sf scores for pain interference with walking ability: participants were asked to circle from any 1 number from 0 (does not interfere) to 10 (completely interferes) that described how, during the past 24 hours, pain has interfered with their walking ability; higher scores indicated higher interference.

BPI-sf is a self-administered questionnaire to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation at specified/scheduled time points. BPI-sf scores for pain interference with sleep: participants were asked to circle from any 1 number from 0 (does not interfere) to 10 (completely interferes) that described how, during the past 24 hours, pain has interfered with their sleep; higher scores indicated higher interference.

BPI-sf is a self-administered questionnaire to assess the severity of pain and pain interference on daily functions during 24 hours prior to evaluation at specified/scheduled time points. BPI-sf scores for pain interference with normal work: participants were asked to circle from any 1 number from 0 (does not interfere) to 10 (completely interferes) that described how, during the past 24 hours, pain has interfered with their normal work; higher scores indicated higher interference.

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. aLBPI: evaluate average pain during the past 24 hours, range 0 (no pain) to 10 (worst possible pain), higher scores = higher worse pain. PGA of low back pain: evaluated participants' well-being due to low back pain on day of assessment, range 1 (very good) to 5 (very poor), higher scores = worse condition. RMDQ total score: assessed ability to perform daily activities, range 0 (no disability) to 24 (maximum disability), higher scores = more disability. Participants were successful responders if they had: >=30 percent reduction in aLBPI from baseline to particular week; decrease of >=30 percent in PGA of low back pain from baseline to particular week and no worsening (increase) in RMDQ total score from baseline to particular week.

PGA of low back pain 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 to 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); 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 positive change of at least 2 points from baseline in PGA of low back pain were reported.

EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.

EQ-5D health state profile has 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses from each of the 5 domains were used to calculate overall health state/a single utility index value. Example: if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined single index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. Japan value sets (with all possible health states) was used in the study, overall health utility score ranged from -0.111 (minimum score) to 1 (maximum score). Higher (positive) scores = better health state.

WPAI:LBP is a 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. Percentage of work time missed by participants due to CLBP was recorded on a score range of 0 (no impact on work time) to 100 (extreme impact on work time), higher scores indicated greater work time missed and lesser productivity.

WPAI: LBP is a 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. Percentage of impairment while working due to CLBP was recorded on a score range of 0 (no impairment) to 100 (extreme impairment), higher scores indicated greater impairment while working and lesser productivity.

WPAI: LBP is a 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. Percentage of overall work impairment due to CLBP was recorded on a score range of 0 (no impairment) to 100 (extreme impairment), higher scores indicated greater overall work impairment and lesser productivity.

WPAI: LBP is a 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. Percentage of daily activity impairment due to CLBP was recorded on a score range of 0 (no impairment) to 100 (extreme impairment), higher scores indicated greater daily activity impairment and lesser productivity.

Number of participants who discontinued from study treatment due to lack of efficacy have been reported here.

Time to discontinuation (in days) 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. Results reported below are contributed only by participants who discontinued due to lack of efficacy.

In case of inadequate pain relief, acetaminophen/paracetamol tablets up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between Day 1 to Week 64. Number of participants with any use of rescue medication during each specified/scheduled study week were summarized.

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 to Week 64. Number of participants with any use of rescue medication during each specified/scheduled study week were summarized.

In case of inadequate pain relief, acetaminophen/paracetamol tablets up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between Day 1 to Week 64. Number of days the participants used the rescue medication during each specified/scheduled study week were summarized.

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 to Week 64. Number of days the participants used the rescue medication during each specified/scheduled study week were summarized.

In case of inadequate pain relief, acetaminophen/paracetamol tablets up to 3000 mg per day up to 3 days in a week could be taken as rescue medication between Day 1 to Week 64. Amount of rescue medication used during each specified/scheduled study week were summarized.

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 to Week 64. Amount of rescue medication used during each specified/scheduled study week were summarized.

Low back pain HCRU assessed utilization of healthcare resources usage during last 3 months (last 3 months before Baseline [Day 1] visit, weeks 64 and 80 visit, via IRT). Visits of services directly related to low back pain evaluated were: visits to primary care physician, neurologist, physician assistant or nurse practitioner, pain specialist, orthopedist, physical therapist, chiropractor, alternative medicine or therapy, nutritionist/dietician, radiologist and other practitioner. Participants might have been counted more than once under various rows. Only those rows have been reported which had at least 1 participant evaluable for any reporting arm.

Low back pain HCRU assessed utilization of healthcare resources during the last 3 months (last 3 months before Baseline [Day 1] visit, weeks 64 and 80 visit, via IRT). Number of participants who visited the emergency room due to low back pain were evaluated.

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.

Low back pain HCRU assessed utilization of healthcare resources during the last 3 months (last 3 months before Baseline [Day 1] visit, weeks 64 and 80 visit, via IRT). Number of nights stayed in the hospital due to low back pain were evaluated.

Low back pain HCRU assessed utilization of healthcare resources during the last 3 months (last 3 months before Baseline [Day 1] visit, weeks 64 and 80 visit, via IRT). Number of participants who used any aids/devices for doing things were evaluated. Aids included walking aid, wheelchair, device or utensil for dress/bathe/eat and any other aids/devices.

Low back pain HCRU assessed utilization of healthcare resources during the last 3 months (last 3 months before Baseline [Day 1] visit, weeks 64 and 80 visit, via IRT). Number of participants who answered as "Yes" for quitting job due to low back pain, were evaluated.

Low back pain HCRU assessed utilization of healthcare resources during the last 3 months (last 3 months before Baseline [Day 1] visit, weeks 64 and 80 visit, via IRT). Domain evaluated was duration (in years) at each specified time point since quitting job due to low back pain.

TSQM v.II: participant rated 11 items questionnaire. Items 1, 2, 7 to 11 were scored as: 1= extremely dissatisfied, 2= very dissatisfied, 3= dissatisfied, 4= somewhat satisfied, 5= satisfied, 6= very satisfied, 7= extremely satisfied. Items 4 to 6 were scored as: 1= extremely dissatisfied, 2= very dissatisfied, 3= somewhat dissatisfied, 4= slightly dissatisfied, 5= not at all dissatisfied. Item 3 was scored as: 0= No, 1= Yes. Four parameters with respect to study medication were evaluated: Effectiveness = ([Item 1+Item 2] - 2 )/12 *100; Side effects = ([Item 4 + Item 5 + Item 6] - 3)/12 *100, if one item is missing then: ([Sum of two completed items]-2]/8 *100; Convenience = ([Item 7 + Item 8 + Item 9] - 3)/18 *100, if one item is missing then: ([Sum of two completed items]-2)/12 *100; Global satisfaction = ([Item 10+Item 11] - 2 ]/12 *100. Each of the 4 parameters had a scale of 0 (no satisfaction) to 100 (best level of satisfaction), higher score = greater satisfaction.

The mPRTI was a self-administered questionnaire containing 4 items to assess participant satisfaction, previous treatment, preference and willingness to continue using the study medication. To assess participants willingness to use study drug again, participants responded using IRT on 5 point Likert scale ranged 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 indicated lesser willingness to use the study drug.

The mPRTI was a self-administered questionnaire containing 4 items to assess participant satisfaction, previous treatment, preference and willingness to continue using the study medication. To assess preference to continue using study drug versus previous treatment, 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 study drug.