Study Of A Controlled Release Formulation Of Pregabalin In Fibromyalgia Patients

Participants who did not maintain at least 30% pain response during the DB phase relative to baseline or were discontinued during DB due to lack of efficacy or an adverse event were considered to have a loss of therapeutic response.

Time frame: Randomization to Week 19

Population: FAS included all participants randomized to the double blind phase who received at least one dose of study medication in the double blind phase.

The time to loss of therapeutic response (LTR) is the time to loss of pain response (\<30% pain response relative to the single-blind (SB) baseline mean pain) or withdrawal due to lack of efficacy or adverse events (in the double blind phase).

Time frame: Randomization to Week 19

Population: Full analysis set (FAS) included all participants randomized to the double blind phase who received at least one dose of study medication in the double blind phase.

The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep.

Time frame: Baseline, Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep.

Time frame: Baseline, Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Total daytime activity = total activity counts during the day.

Time frame: Baseline, Double blind end point visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

The tiredness assessment in the daily IVRS diary consists of an 11-point NRS ranging from zero (not tired) to 10 (extremely tired). Participants rate their tiredness due to fibromyalgia during the past 24 hours by choosing the appropriate number between 0 (not tired) and 10 (extremely tired).

Time frame: Baseline, Double blind endpoint visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

The tiredness assessment in the daily IVRS diary consists of an 11-point NRS ranging from zero (not tired) to 10 (extremely tired). Participants rate their tiredness due to fibromyalgia during the past 24 hours by choosing the appropriate number between 0 (not tired) and 10 (extremely tired).

Time frame: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Participants rated quality of sleep during the past night by selecting a number between 0 (very poor) and 10 (excellent).

Time frame: Baseline, Double blind endpoint visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Participants rated quality of sleep during the past night by selecting a number between 0 (very poor) and 10 (excellent). Mean sleep quality was calculated as the mean of the last seven days, the potential range of responses at each week was therefore 0 (very poor) -10 (excellent), where higher scores indicated better quality of sleep.

Time frame: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night.

Time frame: Baseline, Double blind endpoint visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night.

Time frame: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night.

Time frame: Baseline, Double blind endpoint visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Subjective total sleep time was the subjective estimate of the total amount of time the participant was asleep after lights out until final awakening.

Time frame: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night.

Time frame: Baseline, Double blind endpoint visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night.

Time frame: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

The FIQ is a 20-item self-administered questionnaire. FIQ contains 10 subscales, which are combined to yield a total score. There are 11 questions that are related specifically to physical functioning (item 1). The remaining questions assess pain, fatigue, stiffness, difficulty working, and symptoms of anxiousness and depression. The FIQ is scored from 0 to 100, with higher scores indicating more impairment.

Time frame: Baseline, Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

Time frame: Baseline, Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain).

Time frame: Baseline, Double blind endpoint visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain).

Time frame: Baseline, Weeks 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Population: Full analysis set (FAS) consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep.

Time frame: Baseline, Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

The MOS-SS is a validated self-administered questionnaire consisting of 12 items that assess key constructs of sleep. Instrument scoring yields 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) and two overall sleep problems indices assessing sleep over the past week. Score range for Sleep Disturbance (SD), sleep adequacy (SA), snoring, somnolence, awakening short of breath/headache was 0-100, where higher score=greater SD; greater SA; greater snoring; greater somnolence; greater shortness of breath/headache respectively. Quantity of Sleep (range-0 to 24 hours; higher scores/hours=greater quantity of sleep). Sleep Problem Index I and II: Score Range=0 to 100; higher scores =greater sleep problems. Optimal Sleep (assessed as yes or no), 'Yes' =optimal sleep (average 7-8 hours/night); 'No' =not optimal sleep.

Time frame: Baseline, Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

The MFI is a 20-item, self-administered questionnaire designed to measure the following dimensions of fatigue: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Items are summed to form subscale scores; there is no overall score. The score range is from 4 to 20, where higher scores indicate greater dysfunction.

Time frame: Baseline, Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100. Higher scores indicated a better health-related quality of life.

Time frame: Baseline, Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

Weekly pain scores were calculated from the daily pain diary. Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain).

Time frame: Baseline, Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

WPAI: 6 question participant rated questionnaire to determine the degree to which disease state affected work productivity while at work and affected activities outside of work. Subscale scores include percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity.

Time frame: Baseline, Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse).

Time frame: Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

The questionnaire consists of 3 single-item measures designed to captures the participant's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy.

Time frame: Week 19

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, overall number of participants analyzed signifies participants evaluable for this outcome measure and number analyzed= participants evaluable for specified categories.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100. Higher scores indicated a better health-related quality of life.

Time frame: Baseline, Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

The tiredness assessment in the daily interactive voice response system (IVRS) diary consists of an 11-point NRS ranging from zero (not tired) to 10 (extremely tired). Participants rate their tiredness due to fibromyalgia during the past 24 hours by choosing the appropriate number between 0 (not tired) and 10 (extremely tired).

Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night.

Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication. Here, 'overall number of participants analyzed' signifies participants who awakened after sleep.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night.

Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night. Participants rated quality of sleep during the past night by selecting a number between 0 (very poor) and 10 (excellent). Mean sleep quality was calculated as the mean of the last seven days, the potential range of responses at each week was therefore 0 (very poor) -10 (excellent), where higher scores indicated better quality of sleep.

Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

The SSQ is designed to capture subjective behavior in participants with disrupted sleep. Participants report latency (how long it took them to fall asleep), how many hours they slept, the number of times they woke up, the total wake time after sleep onset, and then rate the quality of their sleep (NRS) for the previous night.

Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

The FIQ is a 20-item self-administered questionnaire. FIQ contains 10 subscales, which are combined to yield a total score. There are 11 questions that are related specifically to physical functioning (item 1). The remaining questions assess pain, fatigue, stiffness, difficulty working, and symptoms of anxiousness and depression. The FIQ is scored from 0 to 100, with higher scores indicating more impairment.

Time frame: Baseline, Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

Time frame: Baseline, Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).

Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6

Population: Single-blind analysis set (SBAS) consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

The MFI is a 20-item, self-administered questionnaire designed to measure the following dimensions of fatigue: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Items are summed to form subscale scores; there is no overall score. The score range is from 4 to 20, where higher scores indicate greater dysfunction.

Time frame: Baseline, Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

Weekly pain scores were calculated from the daily pain diary. Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 NRS: 0 (no pain) to 10 (worst possible pain).

Time frame: Baseline, Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

WPAI: 6 question participant rated questionnaire to determine the degree to which disease state affected work productivity while at work and affected activities outside of work. Subscale scores include percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. Scores scaled as 0 (not affected/no impairment) to 10 (completely affected/impaired). Higher scores indicated greater impairment and less productivity.

Time frame: Baseline, Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

PGIC: participant rated instrument to measure participant's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse).

Time frame: Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication. Here, 'overall number of participants analyzed' signifies participants evaluable for this outcome measure.

The questionnaire consists of 3 single-item measures designed to captures the participant's perception of the effect of treatment in terms of the relative benefit, their satisfaction, and their intention or willingness to continue on therapy.

Time frame: Week 6

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Minutes of interrupted sleep = minutes awake after sleep onset (analogous to wake-time after sleep onset from polysomnography measurements).

Time frame: Baseline, Double blind end point visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Minutes of interrupted sleep = minutes awake after sleep onset (analogous to wake-time after sleep onset from polysomnography measurements).

Time frame: Baseline, Weeks 11, 12, 13, 14 and 15

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Percent sedentary = percent of daytime spent in sedentary activities as determined by the activity counts measured each minute.

Time frame: Baseline, Double blind end point visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Percent sedentary = percent of daytime spent in sedentary activities as determined by the activity counts measured each minute.

Time frame: Baseline, Weeks 11, 12, 13, 14 and 15

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Sleep fragmentation index = a measure of sleep relatedness. Sleep fragmentation index calculated from analysis of the periods that participant was not moving (immobile bouts). It is number of immobile bouts that were exactly 1 minute long divided by total number of immobile bouts. Value ranges from 0-100 percent, with low number representing more restful sleep.

Time frame: Baseline, Double blind end point visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Sleep fragmentation index = a measure of sleep relatedness. Sleep fragmentation index calculated from analysis of the periods that participant was not moving (immobile bouts). It is number of immobile bouts that were exactly 1 minute long divided by total number of immobile bouts. Value ranges from 0-100 percent, with low number representing more restful sleep.

Time frame: Baseline, Weeks 11, 12, 13, 14 and 15

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Total daytime activity = total activity counts during the day.

Time frame: Baseline, Weeks 11, 12, 13, 14 and 15

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Total sleep time = number of minutes asleep between time of sleep onset to morning awakening.

Time frame: Baseline, Double blind end point visit (Week 19)

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Total sleep time = number of minutes asleep between time of sleep onset to morning awakening.

Time frame: Baseline, Weeks 11, 12, 13, 14 and 15

Population: FAS consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase.

C-CASA was used to categorize and summarize results from the Sheehan Suicidality Tracking Scale (S-STS) and the Columbia Suicidality Severity Rating Scale (C-SSRS). S-STS was an 8-item prospective rating scale that tracked treatment-emergent suicidal ideation and behaviors. Items 1a, 2 to 6, 7a, 8 were scored on a 5-point Likert scale (ranges 0 \[not at all\] to 4 \[extremely\]). Items 1, 1b, and 7 required yes or no responses. S-STS total score range 0-30. Lower score=reduced suicidal tendency. C-SSRS was a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Responses on S-STS or C-SSRS were mapped to C-CASA categories as: Completed suicide; suicide attempt; preparatory acts; suicide ideation; self-injurious behavior, intent unknown; not enough information; self-injurious behavior, no suicide intent; other, no deliberate self harm.

Time frame: Week 1 to Week 7 and Week 11 to Week 20

Population: The population in the single and double blind phase consisted of all paticipants who received at least 1 dose of study medication and who received at least 1 dose of study medication.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Sleep fragmentation index = a measure of sleep relatedness. Sleep fragmentation index calculated from analysis of the periods that participant was not moving (immobile bouts). It is number of immobile bouts that were exactly 1 minute long divided by total number of immobile bouts. Value ranges from 0-100 percent, with low number representing more restful sleep.

Time frame: Baseline, Weeks 3, 4, 5, 6 and 7

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Minutes of interrupted sleep = minutes awake after sleep onset (analogous to wake-time after sleep onset from polysomnography measurements).

Time frame: Baseline, Weeks 3, 4, 5, 6 and 7

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Percent sedentary = percent of daytime spent in sedentary activities as determined by the activity counts measured each minute.

Time frame: Baseline, Weeks 3, 4, 5, 6 and 7

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Total daytime activity = total activity counts during the day.

Time frame: Baseline, Weeks 3, 4, 5, 6 and 7

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.

Actigraphy was assessed with an accelerometer that was worn on the wrist. The accelerometer was programmed to record movements. This information was used to calculate several endpoints reflecting daytime activity, and sleep quality and duration. Total sleep time = number of minutes asleep between time of sleep onset to morning awakening.

Time frame: Baseline, Weeks 3, 4, 5, 6 and 7

Population: SBAS consisted of all participants who were enrolled into the SB phase of the study and received at least 1 dose of study medication.