Administered orally

The RMDQ-24 is a health status measure completed by participants to assess physical disability due to low back pain. Participants answered 24 questions about impairment of daily living activities (standing, walking, sitting, wearing clothes, working, etc.) resulting from low back pain. The number of statements marked was summed by the clinician for a total score. The total scores range from 0 (no disability) to 24 (severe disability). LS means calculated using analysis of covariance (ANCOVA) with treatment group as a fixed effect, and baseline value as a covariate.

BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores range from: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores range from: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference is defined as the average of non-missing scores of individual interference items. Higher scores indicated worsening of pain. LS means calculated using MMRM adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.

24-hour average pain severity scores were recorded daily on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). The 11-point Likert scale was also used for assessment of average pain and worst pain within 24-hours. For the analysis, weekly mean was calculated. LS means calculated using MMRM adjusted for treatment, week, interaction between treatment and week as fixed effects and baseline value as covariate.

Pain severity was measured using an 11 point BPI scale from 0 (no pain) to 10 (worst pain) to determine average pain in the past 24 hours (average pain). A 30% (or 50%) improvement was defined as a ≥30% (or ≥50%) reduction in BPI pain severity from baseline to endpoint. Percentage of participants = (number of participants with ≥30% or ≥50% pain reduction / total number of participants in treatment group) * 100.

Pain severity was measured using an 11 point BPI scale from 0 (no pain) to 10(worst pain) to determine average pain in the past 24 hours (average pain). Participants were considered to have sustained pain reduction of ≥30% in the BPI-severity score (average pain) at the time of final evaluation and at least 1 other time point prior to the time of final evaluation compared with baseline, and a reduction of ≥20% from baseline sustained at all evaluation time points between that period. Percentage of participants = (number of participants with sustained pain reduction / total number of participants in treatment group) * 100.

CSI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). LS means calculated using MMRM adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.

BDI-II is a 21-question multiple-choice self-reported inventory about depressive symptoms (sadness, pessimism, past failure, loss of pleasure, guilty feelings, punishment feelings, self-dislike, self-criticalness, suicidal thoughts or wishes, crying, agitation, loss of interest, indecisiveness, worthlessness, loss of energy, changes in sleeping patterns, irritability, changes in appetite, concentration difficulties, tiredness or fatigue, and loss of interest in sex). The scores for each item range from 0 (best) to 3 (worst) with possible total scores of 0 to 63, where higher total scores indicate more severe depressive symptoms. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.

SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.

The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3 level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the Japan population-based algorithm ranging from -0.111 to 1.0, with higher scores indicating better quality of life. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.

WPAI is a self-administered instrument used to measure effect of general health and symptom severity on work productivity and regular activities, and yields 4 types of scores: Absenteeism (work time missed)=Question (Q)2/(Q2+4))*100); Presenteeism (impairment at work/reduced on-the-job effectiveness)=(Q5/10)*100); Work Productivity Loss (overall work impairment/absenteeism plus presenteeism)=(Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)])*100); and Activity Impairment=(Q6/10)*100. Scores range from 0 to 1 for each of the above 4 types; higher scores indicate greater impairment. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.

C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.

Participants evaluated their experience with and details of falls which were recorded. Percentage = (number of participants with fall events) /(total in treatment group) * 100.

Total of all reporting groups

Placebo administered in capsule form orally once every day for 15 weeks.

PGI-I measures a participant's perception of improvement at the time of assessment compared with the start of treatment. Score ranges from 1 (very much better) to 7 (very much worse). LS means calculated using MMRM adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.

The RMDQ-24 is a health status measure completed by participants to assess physical disability due to low back pain. Participants answered 24 questions about impairment of daily living activities (standing, walking, sitting, wearing clothes, working, etc.) resulting from low back pain. The number of statements marked was summed by the clinician for a total score. The total scores range from 0 (no disability) to 24 (severe disability). LS means calculated using analysis of covariance (ANCOVA) with treatment group as a fixed effect, and baseline value as a covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. The last observation carried forward (LOCF) was used.

BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores range from: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores range from: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference is defined as the average of non-missing scores of individual interference items. Higher scores indicated worsening of pain. LS means calculated using MMRM adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.

24-hour average pain severity scores were recorded daily on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). The 11-point Likert scale was also used for assessment of average pain and worst pain within 24-hours. For the analysis, weekly mean was calculated. LS means calculated using MMRM adjusted for treatment, week, interaction between treatment and week as fixed effects and baseline value as covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.

Pain severity was measured using an 11 point BPI scale from 0 (no pain) to 10 (worst pain) to determine average pain in the past 24 hours (average pain). A 30% (or 50%) improvement was defined as a ≥30% (or ≥50%) reduction in BPI pain severity from baseline to endpoint. Percentage of participants = (number of participants with ≥30% or ≥50% pain reduction / total number of participants in treatment group) * 100.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.

Pain severity was measured using an 11 point BPI scale from 0 (no pain) to 10(worst pain) to determine average pain in the past 24 hours (average pain). Participants were considered to have sustained pain reduction of ≥30% in the BPI-severity score (average pain) at the time of final evaluation and at least 1 other time point prior to the time of final evaluation compared with baseline, and a reduction of ≥20% from baseline sustained at all evaluation time points between that period. Percentage of participants = (number of participants with sustained pain reduction / total number of participants in treatment group) * 100.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.

CSI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). LS means calculated using MMRM adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.

BDI-II is a 21-question multiple-choice self-reported inventory about depressive symptoms (sadness, pessimism, past failure, loss of pleasure, guilty feelings, punishment feelings, self-dislike, self-criticalness, suicidal thoughts or wishes, crying, agitation, loss of interest, indecisiveness, worthlessness, loss of energy, changes in sleeping patterns, irritability, changes in appetite, concentration difficulties, tiredness or fatigue, and loss of interest in sex). The scores for each item range from 0 (best) to 3 (worst) with possible total scores of 0 to 63, where higher total scores indicate more severe depressive symptoms. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.

SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.

The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3 level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the Japan population-based algorithm ranging from -0.111 to 1.0, with higher scores indicating better quality of life. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-dose BPI pain severity (average pain) scores. LOCF.

WPAI is a self-administered instrument used to measure effect of general health and symptom severity on work productivity and regular activities, and yields 4 types of scores: Absenteeism (work time missed)=Question (Q)2/(Q2+4))*100); Presenteeism (impairment at work/reduced on-the-job effectiveness)=(Q5/10)*100); Work Productivity Loss (overall work impairment/absenteeism plus presenteeism)=(Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)])*100); and Activity Impairment=(Q6/10)*100. Scores range from 0 to 1 for each of the above 4 types; higher scores indicate greater impairment. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.

FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.

C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.

All randomized participants who received at least 1 dose of study drug, responded no at baseline to the suicide related questionnaire and had data at post-treatment for each question.

Participants evaluated their experience with and details of falls which were recorded. Percentage = (number of participants with fall events) /(total in treatment group) * 100.

All randomized participants who received at least 1 dose of study drug.

Placebo administered in capsule form orally once every day for 15 weeks.