Restless Legs Syndrome
Conditions
Keywords
restless legs syndrome RLS polysomnography PSG sleep disturbance patient reported outcome
Brief summary
The purpose of this study is to assess the efficacy and safety of pregabalin and pramipexole versus placebo in the treatment of restless legs syndrome and associated sleep disturbance.
Interventions
DRUGpregabalin
capsules; 300 mg once-per-day; 4 weeks of treatment
DRUGplacebo
capsules; 0 mg once-per-day; 4 weeks of treatment
DRUGpramipexole
capsules; 0.5 mg once-per-day; 4 weeks of treatment
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of restless legs syndrome with a total score of 15 or more points on the International RLS rating scale (IRLS). * RLS symptoms interfering with sleep on 3 or more nights per week for at least 6 months. * PSG confirmation of WASO of at least 60 min, PLMI of 10 or more, and total sleep time of at least 3 hrs and less than 6.5 hrs.
Exclusion criteria
* Secondary RLS. * Daytime RLS symptoms requiring treatment. * Primary sleep disorder. * Sleep apnea. * Night or shift work. * Concurrent medical disorder that could interfere with efficacy assessment or present a safety concern. * Pregnant or lactating women. * Women of child-bearing potential not using acceptable method of birth control. * Use of prohibited medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wake After Sleep Onset (WASO) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or Early Termination (ET) | WASO as determined by Polysomnography (PSG) was time spent awake from sleep onset to final awakening. WASO= Wake Time During Sleep \[WTDS\] epochs + Wake Time After Sleep \[WTAS\] epochs)/2. WTDS: number of wake epochs (30 seconds of PSG recording) after onset of persistent sleep and prior to final awakening or end of 8-hour recording/2 and WTAS: number of wake epochs after final awakening until end of the 8-hour recording/2. WASO was measured on 2 consecutive days within a period. Arithmetic mean of WASO of each participant for all periods was taken prior to employing linear mixed model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Periodic Limb Movement Arousal Index (PLMAI) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | PLMAI, as determined by PSG was number of periodic limb movements leading to arousal per hour (per hour of Total Sleep Time \[TST\]). Arithmetic mean of PLMAI of each participant for all periods was taken prior to employing linear mixed model. |
| Subjective Total Sleep Time (sTST) | Week 3 and Week 5 of Each Intervention Period or ET | sTST as derived from Subjective Sleep Questionnaire (SSQ), a participant reported subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. Completed by the participant 30 minutes after waking; recall period is the night before. Arithmetic mean of sTST of each participant for all periods was taken prior to employing linear mixed model. |
| Minutes of Stage N1, N2, N3 and R Sleep | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | Minutes of Stage 1 Non-Rapid Eye Movement (Non-REM) sleep (Stage N1), Stage 2 Non-REM sleep (Stage N2), Stage 3 Non-REM sleep (Stage N3) or Slow Wave Sleep (SWS) and Stage REM (Stage R) sleep, as determined by PSG were calculated as total number of Stage N1 30-second (30-sec) epochs divided by 2, total number of Stage N2 30-sec epochs divided by 2, total number of Stage N3 30-sec epochs divided by 2 and total number of Stage R 30-sec epochs divided by 2 respectively. Arithmetic mean of minutes of stage N1, N2, N3 and R sleep of each participant for all periods was taken prior to employing linear mixed model. |
| Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage 2 Non-REM \[Stage N2\] 30-second (30-sec) epoch, Stage 3 Non-REM \[Stage N3\] 30-sec epoch, or stage rapid eye movement \[stage R\] 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model. |
| Restless Legs Syndrome-Next Day Impact (RLS-NDI) | Week 3 and Week 5 of Each Intervention Period or ET | RLS-NDI:participant-rated instrument to assess daytime performance and participant's previous night's sleep, consists of 14 items encompassing 5 domains:tiredness;emotional functioning;social functioning;cognitive functioning;activities of daily living and 1 global item for overall well-being. Each item: 0-10 scale; 0=Not at all; 10=Extremely. Total score: sum of scores from question 1-14 (question 10, 11: scores reversed). Total score range: 0-140; higher scores: more severe impact. Arithmetic mean of RLS-NDI of each participant for all periods was taken prior to employing linear mixed model. |
| Periodic Limb Movement Index (PLMI) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | PLMI, as determined by PSG was number of periodic limb movements per hour based on time in bed (TIB). Arithmetic mean of PLMI of each participant for all periods was taken prior to employing linear mixed model. |
| Periodic Limb Movement in Sleep Index (PLMSI) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | PLMSI, as determined by PSG was number of periodic limb movements in sleep per hour based on TST. Arithmetic mean of PLMSI of each participant for all periods was taken prior to employing linear mixed model. |
| Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30-sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model. |
| Number of Arousals (NASO) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | NASO, as determined by PSG, was calculated as number of times there is a shift from a stage N2 to N3 or R 30-sec epoch to a stage N1 30-sec epoch from the onset of persistent sleep to light on. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NASO of each participant for all periods was taken prior to employing linear mixed model. |
| International Restless Legs Syndrome Study Group Rating Scale (IRLS) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | IRLS: psychometrically; clinically valid; clinician-administered instrument assesses severity of RLS. RLS symptom severity and impact on daily living comprise of 10 items giving 2 subscale scores and 1 global score. Subscale scores: symptom severity(6 items) and impact on daily living(3 items), item 3 loaded equally on both subscales. Global score calculated from 10 items. Score of all items range from 0-4, total score range:0-40. Lower scores: lower severity and better quality of life. Arithmetic mean of IRLS of each participant for all periods was taken prior to employing linear mixed model. |
| Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) Scale | Baseline, Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | CGI-I: 7-point clinician rated scale to assess improvement in disease condition as compared to the start of the study medication (baseline), ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved). Higher score = more affected. |
| Latency to Stage R Sleep (LREM) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | LREM, as determined by PSG, was number of non-wake epochs from the beginning of the recording to the first occurrence of Stage R sleep divided by 2. Arithmetic mean of LREM of each participant for all periods was taken prior to employing linear mixed model. |
| Latency to Persistent Sleep (LPS) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | LPS, as determined by PSG, was number of epochs from the beginning of the recording (lights-out) to the start of the first 20 consecutive non-wake epochs (10 minutes of persistent sleep) divided by 2. Arithmetic mean of LPS of each participant for all periods was taken prior to employing linear mixed model. |
| Wake Time During Sleep (WTDS) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | WTDS, as determined by PSG, was the number of wake (30-sec) epochs after the onset of persistent sleep and prior to the final awakening or at the end of 8-hour recording. WTDS was the sum of 2 consecutive days of recordings divided by 2 at the end of each intervention period. Arithmetic mean of WTDS of each participant for all periods was taken prior to employing linear mixed model. |
| Arousal Index (NASOI) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | Arousal index, as determined by PSG, was NASO per hours of sleep from the onset of persistent sleep to light on. Arithmetic mean of NASOI of each participant for all periods was taken prior to employing linear mixed model. |
| Total Sleep Time (TST) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | TST, as determined by PSG, was the number of non-wake (30-sec) epochs from the beginning of recording to the end of the recording. TST was the sum of 2 consecutive days of recording divided by 2 at the end of each intervention period. Arithmetic mean of TST of each participant for all periods was taken prior to employing linear mixed model. |
| Sleep Efficiency (SE) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | SE, as determined by PSG, was the TST divided by the time in bed (TIB)(both in minutes), multiplied by 100. Sum of 2 consecutive days of recording divided by 2 at the end of each intervention period. Arithmetic mean of SE of each participant for all periods was taken prior to employing linear mixed model. |
| Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | WASO, as determined by PSG was time spent awake from sleep onset to final awakening. WASO = (sum of WTDS 30-sec epochs and WTAS 30-sec epochs)/2, measured on 2 consecutive days at end of each intervention period by each individual hour (8 hours total) and each individual quarter of night (eight hours in 2 hour increments). Arithmetic mean of WASO of each participant for all periods was taken prior to employing linear mixed model. |
| Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 30-sec epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model. |
| Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30-sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model. |
| Hourly and Quarterly Assessment of Number of Arousals (NASO) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | NASO, as determined by PSG was the number of times there is a shift from a stage N2 to N3 or R 30-sec epoch to a stage N1 30-sec epoch from the onset of persistent sleep to light on. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NASO for each participant at each period was taken prior to employing linear mixed model. |
| Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | PLM, as determined by PSG was number of periodic limb movements based on time in bed (TIB). Calculated at each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of PLM of each participant for all periods was taken prior to employing linear mixed model. |
| Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | SE, as determined by PSG, was the TST divided by the time in bed (TIB)(both in minutes), multiplied by 100. Sum of 2 consecutive days of recording divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean for SE of each participant for all periods was taken prior to employing linear mixed model. |
| Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale | Week 3 and Week 5 of Each Intervention Period or ET | SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items giving 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This (1 item) subscale: numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0 awakenings to 30 awakenings. Lower value indicates better quality of sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST. |
| Subjective Sleep Questionnaire (SSQ): Total Wake Time After Sleep Onset Subscale | Week 3 and Week 5 of each intervention period or ET | SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This 1 item subscale (in minutes): numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0-1440 minutes. Lower value: better sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST. |
| Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale | Week 3 and Week 5 of each intervention period or ET | SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This 1 item subscale: numerical rating completed by participant 30 minutes after waking; recall period: night before, Range: 0 to 100, higher score: better quality of sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST. |
| Subjective Sleep Questionnaire (SSQ): Latency Subscale | Week 3 and Week 5 of each intervention period or ET | SSQ: participant-rated instrument assesses sleep behavior; measures sleep quantity, quality. Comprised of 5 items giving 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. Latency (time to fall asleep \[in minutes\]): numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0 - 840 minutes, lower value: better sleep. Arithmetic mean of subscale score of each participant for all periods was taken prior to employing linear mixed model. Hours of sleep subscale results reported as sTST. |
| Medical Outcomes Study - Sleep Scale (MOS-SS) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | MOS-SS:Participant rated instrument, assesses sleep quantity, quality;with 12 items(7 subscale scores:sleep disturbance, snoring, awakening short of breath/with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep;2 composite index scores:sleep problems Index I, II). Subscale scores total range:0-100(except sleep quantity\[range 0-24 hours\], optimal sleep\[range 0-1: 0= \<7 or \>8 hours;1=7/8 hours\]). Higher scores=poorer sleep outcomes(except sleep quantity, adequacy). Arithmetic mean of MOS-SS scores of each participant for all periods was taken before linear mixed model analysis. |
| Restless Leg Syndrome - Quality of Life Scale (RLS-QoL) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | RLS-QoL: psychometrically and clinically valid and reliable participant-rated instrument, assesses impact of RLS on participant quality of life. Specifically, it assessed effects of RLS on health status function (symptom severity, daily activity, social functioning, sleep, concentrating and decision making, travelling, sexual activity, and work) giving a summary score ranging from 0-100. Higher scores reflect better quality of life. Recall period: 1 week prior to assessment. Arithmetic mean of RLS-QoL score of each participant for all periods was taken prior to employing linear mixed model. |
| Wake Time After Sleep (WTAS) | Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET | WTAS, as determined by PSG, was the number of wake (30-sec) epochs after the final awakening until the end of the 8-hour recording. WTAS was the sum of 2 consecutive days of recordings divided by 2 at the end of each intervention period. Arithmetic mean of WTAS of each participant for all periods was taken prior to employing linear mixed model. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Then Pramipexole 0.5 mg Then Pregabalin 300 mg Placebo (PBO) capsule matched to pramipexole (PPX) 0.5 milligram (mg) once daily or pregabalin (PGB) 300 mg once daily (matching placebo escalation and tapering scheme was followed) in first intervention period then PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in second intervention period and PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period. | 15 |
| Pramipexole 0.5 mg Then Pregabalin 300 mg Then Placebo PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in first intervention period then PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in second intervention period and PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in third intervention period. A PBO wash-out period of 7 days was maintained between each period. | 13 |
| Pregabalin 300 mg Then Placebo Then Pramipexole 0.5 mg PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in first intervention period then PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in second intervention period and PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period. | 14 |
| Pregabalin 300 mg Then Pramipexole 0.5 mg Then Placebo PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in first intervention period then PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in second intervention period and PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in third intervention period. A PBO wash-out period of 7 days was maintained between each period. | 15 |
| Placebo Then Pregabalin 300 mg Then Pramipexole 0.5 mg PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in first intervention period then PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in second intervention period and PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period. | 15 |
| Pramipexole 0.5 mg Then Placebo Then Pregabalin 300 mg PPX capsule 0.5 mg once daily following a 2 week up escalation, Day 1-5: 0.125 mg; Day 6-10: 0.25 mg and Day 11 onwards: 0.5 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 0.25 mg and Day 4-6: 0.125 mg) in first intervention period then PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily (matching placebo escalation and tapering scheme was followed) in second intervention period and PGB capsule 300 mg once daily following a 2 week up escalation, Day 1-5: 75 mg; Day 6-10: 150 mg and Day 11 onwards: 300 mg fixed dose for 19 days followed by tapering schedule (Day 1-3: 150 mg and Day 4-6: 75 mg) in third intervention period. A PBO wash-out period of 7 days was maintained between each period. | 13 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Intervention Period | Adverse Event | 0 | 1 | 0 | 1 | 0 | 0 |
| First Intervention Period | Insufficient clinical response | 0 | 0 | 0 | 0 | 1 | 0 |
| First Intervention Period | Lost to Follow-up | 0 | 1 | 0 | 1 | 0 | 0 |
| First Intervention Period | Other | 0 | 0 | 0 | 1 | 1 | 0 |
| First Intervention Period | Protocol Violation | 0 | 0 | 0 | 0 | 2 | 0 |
| First Intervention Period | Withdrawal by Subject | 0 | 1 | 0 | 1 | 0 | 1 |
| Second Intervention Period | Adverse Event | 0 | 2 | 0 | 1 | 1 | 0 |
| Second Intervention Period | Other | 0 | 0 | 0 | 1 | 0 | 1 |
| Second Intervention Period | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Third Intervention Period | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
| Third Intervention Period | Other | 0 | 0 | 0 | 0 | 0 | 1 |
| Third Intervention Period | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Third Intervention Period | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Pregabalin 300 mg Then Placebo Then Pramipexole 0.5 mg | Pramipexole 0.5 mg Then Pregabalin 300 mg Then Placebo | Placebo Then Pramipexole 0.5 mg Then Pregabalin 300 mg | Total | Pramipexole 0.5 mg Then Placebo Then Pregabalin 300 mg | Placebo Then Pregabalin 300 mg Then Pramipexole 0.5 mg | Pregabalin 300 mg Then Pramipexole 0.5 mg Then Placebo |
|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 44 years | 1 participants | 4 participants | 3 participants | 18 participants | 3 participants | 5 participants | 2 participants |
| Age, Customized 45 to 64 years | 11 participants | 7 participants | 8 participants | 52 participants | 8 participants | 8 participants | 10 participants |
| Age, Customized Greater than or equal to 65 years | 2 participants | 2 participants | 4 participants | 15 participants | 2 participants | 2 participants | 3 participants |
| Age, Customized Less than 18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 11 Participants | 54 Participants | 7 Participants | 12 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 4 Participants | 31 Participants | 6 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 46 / 75 | 40 / 76 | 27 / 73 |
| serious Total, serious adverse events | 2 / 75 | 1 / 76 | 3 / 73 |
Outcome results
Primary
Wake After Sleep Onset (WASO)
WASO as determined by Polysomnography (PSG) was time spent awake from sleep onset to final awakening. WASO= Wake Time During Sleep \[WTDS\] epochs + Wake Time After Sleep \[WTAS\] epochs)/2. WTDS: number of wake epochs (30 seconds of PSG recording) after onset of persistent sleep and prior to final awakening or end of 8-hour recording/2 and WTAS: number of wake epochs after final awakening until end of the 8-hour recording/2. WASO was measured on 2 consecutive days within a period. Arithmetic mean of WASO of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or Early Termination (ET)
Population: Intent to Treat (ITT) population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Wake After Sleep Onset (WASO) | 51.50 minutes |
| Pramipexole 0.5 mg | Wake After Sleep Onset (WASO) | 78.42 minutes |
| Placebo | Wake After Sleep Onset (WASO) | 78.60 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The least squares (LS) means and standard errors (SE) were used to test for a treatment difference and construct 2-sided 95% confidence intervals (CIs). The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-35.78, -18.42]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-35.54, -18.32]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.968495% CI: [-8.72, 8.38]Mixed Models Analysis
Secondary
Arousal Index (NASOI)
Arousal index, as determined by PSG, was NASO per hours of sleep from the onset of persistent sleep to light on. Arithmetic mean of NASOI of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Arousal Index (NASOI) | 2.75 arousals/hour |
| Pramipexole 0.5 mg | Arousal Index (NASOI) | 4.18 arousals/hour |
| Placebo | Arousal Index (NASOI) | 3.44 arousals/hour |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.005695% CI: [-1.17, -0.21]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-1.9, -0.95]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.002695% CI: [0.26, 1.21]Mixed Models Analysis
Secondary
Hourly and Quarterly Assessment of Number of Arousals (NASO)
NASO, as determined by PSG was the number of times there is a shift from a stage N2 to N3 or R 30-sec epoch to a stage N1 30-sec epoch from the onset of persistent sleep to light on. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NASO for each participant at each period was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. Here n signifies number of participants analyzed at that particular time point for each arm group respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 8 (n= 67, 71, 68) | 2.07 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 1 (n= 66, 67, 66) | 1.48 arousals | 95% Confidence Interval 1.65 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 3 (n= 67, 70, 67) | 2.31 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 7 (n= 67, 71, 68) | 2.15 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 2 (n= 67, 70, 68) | 5.25 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 6 (n= 67, 71, 68) | 2.39 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 2 (n= 67, 70, 66) | 2.36 arousals | 95% Confidence Interval 2.03 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 5 (n= 67, 70, 68) | 2.33 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 3 (n= 67, 71, 68) | 4.75 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 1 (n= 67, 70, 66) | 3.75 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 4 (n= 67, 71, 68) | 4.23 arousals | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 4 (n= 67, 70, 68) | 2.94 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 5 (n= 67, 70, 68) | 3.20 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 3 (n= 67, 70, 67) | 3.23 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 4 (n= 67, 70, 68) | 3.41 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 6 (n= 67, 71, 68) | 3.30 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 4 (n= 67, 71, 68) | 6.24 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 1 (n= 66, 67, 66) | 2.06 arousals | 95% Confidence Interval 2.22 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 2 (n= 67, 70, 66) | 3.23 arousals | 95% Confidence Interval 2.15 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 7 (n= 67, 71, 68) | 3.28 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 8 (n= 67, 71, 68) | 2.98 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 1 (n= 67, 70, 66) | 5.09 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 2 (n= 67, 70, 68) | 6.67 arousals | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 3 (n= 67, 71, 68) | 6.44 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 4 (n= 67, 71, 68) | 5.13 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 2 (n= 67, 70, 68) | 5.55 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 8 (n= 67, 71, 68) | 2.46 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 6 (n= 67, 71, 68) | 2.70 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 3 (n= 67, 70, 67) | 2.80 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 1 (n= 67, 70, 66) | 4.26 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 4 (n= 67, 70, 68) | 2.76 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 5 (n= 67, 70, 68) | 2.89 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 2 (n= 67, 70, 66) | 2.68 arousals | 95% Confidence Interval 1.99 |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 1 (n= 66, 67, 66) | 1.79 arousals | 95% Confidence Interval 1.78 |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Quarter 3 (n= 67, 71, 68) | 5.61 arousals | — |
| Placebo | Hourly and Quarterly Assessment of Number of Arousals (NASO) | Hour 7 (n= 67, 71, 68) | 2.66 arousals | — |
Secondary
Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1)
NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 30-sec epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. Here n signifies number of participants analyzed at that particular time point for each arm group respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 1 (n= 67, 70, 66) | 2.71 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 4 (n= 67, 70, 68) | 2.44 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 1 (n= 66, 67, 66) | 0.70 awakenings | 95% Confidence Interval 0.9 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 7 (n= 67, 71, 68) | 3.07 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 5 (n= 67, 70, 68) | 2.47 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 6 (n= 67, 71, 68) | 2.91 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 8 (n= 67, 71, 68) | 2.76 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 3 (n= 67, 71, 68) | 5.39 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 2 (n= 67, 70, 66) | 2.06 awakenings | 95% Confidence Interval 1.41 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 2 (n= 67, 70, 68) | 4.53 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 3 (n= 67, 70, 67) | 2.09 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 4 (n= 67, 71, 68) | 5.87 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 2 (n= 67, 70, 66) | 3.32 awakenings | 95% Confidence Interval 1.74 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 5 (n= 67, 70, 68) | 3.76 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 8 (n= 67, 71, 68) | 3.46 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 1 (n= 66, 67, 66) | 1.39 awakenings | 95% Confidence Interval 1.12 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 3 (n= 67, 70, 67) | 3.42 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 4 (n= 67, 70, 68) | 3.83 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 6 (n= 67, 71, 68) | 3.68 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 7 (n= 67, 71, 68) | 4.04 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 1 (n= 67, 70, 66) | 4.61 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 2 (n= 67, 70, 68) | 7.27 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 3 (n= 67, 71, 68) | 7.37 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 4 (n= 67, 71, 68) | 7.36 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 3 (n= 67, 70, 67) | 2.66 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 3 (n= 67, 71, 68) | 6.04 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 1 (n= 67, 70, 66) | 3.49 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 2 (n= 67, 70, 66) | 2.47 awakenings | 95% Confidence Interval 1.44 |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 5 (n= 67, 70, 68) | 2.87 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 2 (n= 67, 70, 68) | 5.32 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 1 (n= 66, 67, 66) | 1.10 awakenings | 95% Confidence Interval 0.76 |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 6 (n= 67, 71, 68) | 3.16 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 4 (n= 67, 70, 68) | 2.71 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Quarter 4 (n= 67, 71, 68) | 6.44 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 7 (n= 67, 71, 68) | 3.32 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | Hour 8 (n= 67, 71, 68) | 3.11 awakenings | — |
Secondary
Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2)
NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30-sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. Here n signifies number of participants analyzed at that particular time point for each arm group respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 8 (n= 67, 71, 68) | 1.00 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 5 (n= 67, 70, 68) | 1.06 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 1 (n= 66, 67, 66) | 0.42 awakenings | 95% Confidence Interval 0.6 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 1 (n= 67, 70, 66) | 1.43 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 4 (n= 67, 71, 68) | 2.25 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 3 (n= 67, 71, 68) | 2.10 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 2 (n= 67, 70, 68) | 1.99 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 6 (n= 67, 71, 68) | 1.02 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 3 (n= 67, 70, 67) | 0.99 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 7 (n= 67, 71, 68) | 1.24 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 4 (n= 67, 70, 68) | 1.01 awakenings | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 2 (n= 67, 70, 66) | 1.04 awakenings | 95% Confidence Interval 0.83 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 2 (n= 67, 70, 66) | 1.72 awakenings | 95% Confidence Interval 1.13 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 5 (n= 67, 70, 68) | 1.76 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 6 (n= 67, 71, 68) | 1.57 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 7 (n= 67, 71, 68) | 1.94 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 8 (n= 67, 71, 68) | 1.56 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 1 (n= 67, 70, 66) | 2.27 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 2 (n= 67, 70, 68) | 3.56 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 1 (n= 66, 67, 66) | 0.61 awakenings | 95% Confidence Interval 0.71 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 3 (n= 67, 70, 67) | 1.71 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 4 (n= 67, 70, 68) | 1.84 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 3 (n= 67, 71, 68) | 3.30 awakenings | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 4 (n= 67, 71, 68) | 3.44 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 7 (n= 67, 71, 68) | 1.57 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 6 (n= 67, 71, 68) | 1.44 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 3 (n= 67, 71, 68) | 2.92 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 3 (n= 67, 70, 67) | 1.41 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 2 (n= 67, 70, 66) | 1.37 awakenings | 95% Confidence Interval 1.06 |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 4 (n= 67, 70, 68) | 1.48 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 5 (n= 67, 70, 68) | 1.48 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 2 (n= 67, 70, 68) | 2.85 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 1 (n= 67, 70, 66) | 2.06 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 8 (n= 67, 71, 68) | 1.28 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Quarter 4 (n= 67, 71, 68) | 2.86 awakenings | — |
| Placebo | Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) | Hour 1 (n= 66, 67, 66) | 0.73 awakenings | 95% Confidence Interval 0.59 |
Secondary
Hourly and Quarterly Assessment of Periodic Limb Movement (PLM)
PLM, as determined by PSG was number of periodic limb movements based on time in bed (TIB). Calculated at each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of PLM of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least one dose of study medication and had at least one post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 8 | 13.37 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 4 | 30.35 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 1 | 57.82 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 3 | 46.77 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 5 | 25.70 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 2 | 71.29 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 4 | 27.60 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 6 | 21.02 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 3 | 40.93 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 1 | 31.45 movement/hour | 95% Confidence Interval 29.7 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 7 | 14.22 movement/hour | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 2 | 26.38 movement/hour | 95% Confidence Interval 29.2 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 7 | 11.11 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 8 | 16.55 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 2 | 12.49 movement/hour | 95% Confidence Interval 14.51 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 2 | 28.55 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 1 | 34.02 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 3 | 22.49 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 3 | 14.05 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 4 | 14.50 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 1 | 21.57 movement/hour | 95% Confidence Interval 27.03 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 5 | 11.93 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 6 | 10.57 movement/hour | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 4 | 27.64 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 4 | 48.01 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 1 | 54.67 movement/hour | 95% Confidence Interval 39.98 |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 3 | 48.76 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 1 | 107.56 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 2 | 52.93 movement/hour | 95% Confidence Interval 40.92 |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 4 | 46.58 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 5 | 36.17 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 6 | 32.47 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 7 | 27.04 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Hour 8 | 20.97 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 2 | 95.31 movement/hour | — |
| Placebo | Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) | Quarter 3 | 68.66 movement/hour | — |
Secondary
Hourly and Quarterly Assessment of Sleep Efficiency (SE)
SE, as determined by PSG, was the TST divided by the time in bed (TIB)(both in minutes), multiplied by 100. Sum of 2 consecutive days of recording divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean for SE of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least one dose of study medication and had at least one post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 2 | 86.13 percentage of time asleep | 95% Confidence Interval 16.94 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 3 | 90.22 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 4 | 89.41 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 7 | 84.70 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 2 | 89.84 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 4 | 81.37 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 1 | 62.31 percentage of time asleep | 95% Confidence Interval 24.14 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 5 | 90.00 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 6 | 90.33 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 8 | 78.07 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 1 | 74.21 percentage of time asleep | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 3 | 90.09 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 1 | 75.15 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 2 | 83.43 percentage of time asleep | 95% Confidence Interval 16.03 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 1 | 66.88 percentage of time asleep | 95% Confidence Interval 24.3 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 4 | 75.16 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 3 | 84.86 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 3 | 81.74 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 6 | 81.64 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 4 | 79.84 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 8 | 69.51 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 2 | 82.37 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 5 | 81.85 percentage of time asleep | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 7 | 80.90 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 5 | 82.92 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 1 | 67.62 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 3 | 82.75 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 4 | 74.84 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 1 | 57.80 percentage of time asleep | 95% Confidence Interval 22.9 |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 4 | 82.61 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 8 | 69.75 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 2 | 77.31 percentage of time asleep | 95% Confidence Interval 20.49 |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Quarter 2 | 82.30 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 3 | 81.86 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 6 | 82.49 percentage of time asleep | — |
| Placebo | Hourly and Quarterly Assessment of Sleep Efficiency (SE) | Hour 7 | 79.86 percentage of time asleep | — |
Secondary
Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO)
WASO, as determined by PSG was time spent awake from sleep onset to final awakening. WASO = (sum of WTDS 30-sec epochs and WTAS 30-sec epochs)/2, measured on 2 consecutive days at end of each intervention period by each individual hour (8 hours total) and each individual quarter of night (eight hours in 2 hour increments). Arithmetic mean of WASO of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. Here n signifies number of participants analyzed at that particular time point for each arm group respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 4 (n= 67, 70, 68) | 6.21 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 1 (n= 67, 70, 66) | 6.42 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 6 (n= 67, 71, 68) | 5.78 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 5 (n= 67, 70, 68) | 5.93 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 3 (n= 67, 71, 68) | 11.81 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 1 (n= 66, 67, 66) | 1.62 minutes | 95% Confidence Interval 4.12 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 4 (n= 67, 71, 68) | 22.37 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 8 (n= 67, 71, 68) | 13.16 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 2 (n= 67, 70, 66) | 5.04 minutes | 95% Confidence Interval 6.15 |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 2 (n= 67, 70, 68) | 11.08 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 7 (n= 67, 71, 68) | 9.18 minutes | — |
| Pregabalin 300 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 3 (n= 67, 70, 67) | 4.89 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 3 (n= 67, 70, 67) | 8.23 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 1 (n= 66, 67, 66) | 2.26 minutes | 95% Confidence Interval 2.69 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 2 (n= 67, 70, 66) | 7.07 minutes | 95% Confidence Interval 5.48 |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 4 (n= 67, 70, 68) | 11.54 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 5 (n= 67, 70, 68) | 10.39 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 6 (n= 67, 71, 68) | 10.54 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 7 (n= 67, 71, 68) | 11.44 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 8 (n= 67, 71, 68) | 18.27 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 1 (n= 67, 70, 66) | 8.99 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 2 (n= 67, 70, 68) | 19.77 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 3 (n= 67, 71, 68) | 20.77 minutes | — |
| Pramipexole 0.5 mg | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 4 (n= 67, 71, 68) | 29.55 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 1 (n= 66, 67, 66) | 3.35 minutes | 95% Confidence Interval 3.84 |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 4 (n= 67, 71, 68) | 30.21 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 3 (n= 67, 71, 68) | 20.55 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 1 (n= 67, 70, 66) | 10.35 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 8 (n= 67, 71, 68) | 18.15 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 5 (n= 67, 70, 68) | 10.04 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 4 (n= 67, 70, 68) | 9.52 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 3 (n= 67, 70, 67) | 8.90 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 6 (n= 67, 71, 68) | 10.52 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 2 (n= 67, 70, 66) | 7.39 minutes | 95% Confidence Interval 6.85 |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Quarter 2 (n= 67, 70, 68) | 18.18 minutes | — |
| Placebo | Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) | Hour 7 (n= 67, 71, 68) | 12.09 minutes | — |
Secondary
International Restless Legs Syndrome Study Group Rating Scale (IRLS)
IRLS: psychometrically; clinically valid; clinician-administered instrument assesses severity of RLS. RLS symptom severity and impact on daily living comprise of 10 items giving 2 subscale scores and 1 global score. Subscale scores: symptom severity(6 items) and impact on daily living(3 items), item 3 loaded equally on both subscales. Global score calculated from 10 items. Score of all items range from 0-4, total score range:0-40. Lower scores: lower severity and better quality of life. Arithmetic mean of IRLS of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | International Restless Legs Syndrome Study Group Rating Scale (IRLS) | 12.28 units on a scale |
| Pramipexole 0.5 mg | International Restless Legs Syndrome Study Group Rating Scale (IRLS) | 15.35 units on a scale |
| Placebo | International Restless Legs Syndrome Study Group Rating Scale (IRLS) | 18.38 units on a scale |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-8.1, -4.09]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.002995% CI: [-5.07, -1.07]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.003295% CI: [-5.02, -1.04]Mixed Models Analysis
Secondary
Latency to Persistent Sleep (LPS)
LPS, as determined by PSG, was number of epochs from the beginning of the recording (lights-out) to the start of the first 20 consecutive non-wake epochs (10 minutes of persistent sleep) divided by 2. Arithmetic mean of LPS of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Latency to Persistent Sleep (LPS) | 31.13 minutes |
| Pramipexole 0.5 mg | Latency to Persistent Sleep (LPS) | 31.52 minutes |
| Placebo | Latency to Persistent Sleep (LPS) | 38.86 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.10495% CI: [-17.07, 1.61]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.932595% CI: [-9.67, 8.87]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.117595% CI: [-16.54, 1.87]Mixed Models Analysis
Secondary
Latency to Stage R Sleep (LREM)
LREM, as determined by PSG, was number of non-wake epochs from the beginning of the recording to the first occurrence of Stage R sleep divided by 2. Arithmetic mean of LREM of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Latency to Stage R Sleep (LREM) | 95.22 minutes |
| Pramipexole 0.5 mg | Latency to Stage R Sleep (LREM) | 130.99 minutes |
| Placebo | Latency to Stage R Sleep (LREM) | 84.52 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.167795% CI: [-4.56, 25.95]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-50.88, -20.66]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [31.45, 61.48]Mixed Models Analysis
Secondary
Medical Outcomes Study - Sleep Scale (MOS-SS)
MOS-SS:Participant rated instrument, assesses sleep quantity, quality;with 12 items(7 subscale scores:sleep disturbance, snoring, awakening short of breath/with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep;2 composite index scores:sleep problems Index I, II). Subscale scores total range:0-100(except sleep quantity\[range 0-24 hours\], optimal sleep\[range 0-1: 0= \<7 or \>8 hours;1=7/8 hours\]). Higher scores=poorer sleep outcomes(except sleep quantity, adequacy). Arithmetic mean of MOS-SS scores of each participant for all periods was taken before linear mixed model analysis.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. Here n signifies number of participants analyzed for particular subscale for each arm group respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Awaken Short of Breath/with Headache (n= 68,71,69) | 11.59 units on a scale |
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Adequacy (n= 68,71,69) | 54.96 units on a scale |
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Sleep Quantity (n= 68,71,69) | 6.43 units on a scale |
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | 9-Item Sleep Problems Index (n= 68,71,69) | 32.75 units on a scale |
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Somnolence (n= 68,71,69) | 21.28 units on a scale |
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | 6-Item Sleep Problems Index (n= 68,71,69) | 30.69 units on a scale |
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Optimal Sleep (n= 68,71,69) | 0.43 units on a scale |
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Sleep Disturbance (n= 68,71,69) | 34.08 units on a scale |
| Pregabalin 300 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Snoring (n= 67,71,68) | 15.27 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Optimal Sleep (n= 68,71,69) | 0.35 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Snoring (n= 67,71,68) | 15.97 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Awaken Short of Breath/with Headache (n= 68,71,69) | 13.10 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Adequacy (n= 68,71,69) | 43.90 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Sleep Quantity (n= 68,71,69) | 6.50 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Somnolence (n= 68,71,69) | 21.32 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | 6-Item Sleep Problems Index (n= 68,71,69) | 37.24 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | Sleep Disturbance (n= 68,71,69) | 40.19 units on a scale |
| Pramipexole 0.5 mg | Medical Outcomes Study - Sleep Scale (MOS-SS) | 9-Item Sleep Problems Index (n= 68,71,69) | 37.88 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | 9-Item Sleep Problems Index (n= 68,71,69) | 42.89 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | Sleep Quantity (n= 68,71,69) | 5.97 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | Snoring (n= 67,71,68) | 17.96 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | 6-Item Sleep Problems Index (n= 68,71,69) | 40.59 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | Awaken Short of Breath/with Headache (n= 68,71,69) | 10.88 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | Sleep Disturbance (n= 68,71,69) | 48.65 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | Adequacy (n= 68,71,69) | 40.79 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | Optimal Sleep (n= 68,71,69) | 0.29 units on a scale |
| Placebo | Medical Outcomes Study - Sleep Scale (MOS-SS) | Somnolence (n= 68,71,69) | 23.71 units on a scale |
Comparison: Awaken Short of Breath/with Headache: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.694795% CI: [-2.85, 4.27]Mixed Models Analysis
Comparison: Awaken Short of Breath/with Headache: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.39895% CI: [-5.06, 2.02]Mixed Models Analysis
Comparison: Awaken Short of Breath/with Headache: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.214495% CI: [-1.3, 5.76]Mixed Models Analysis
Comparison: Adequacy: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.000695% CI: [6.25, 22.08]Mixed Models Analysis
Comparison: Adequacy: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.006195% CI: [3.22, 18.92]Mixed Models Analysis
Comparison: Adequacy: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.434295% CI: [-4.72, 10.93]Mixed Models Analysis
Comparison: Somnolence: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.24295% CI: [-6.53, 1.66]Mixed Models Analysis
Comparison: Somnolence: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.98195% CI: [-4.12, 4.02]Mixed Models Analysis
Comparison: Somnolence: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.246895% CI: [-6.44, 1.67]Mixed Models Analysis
Comparison: Sleep Quantity: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.149695% CI: [-0.17, 1.09]Mixed Models Analysis
Comparison: Sleep Quantity: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.818495% CI: [-0.69, 0.55]Mixed Models Analysis
Comparison: Sleep Quantity: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.091895% CI: [-0.09, 1.15]Mixed Models Analysis
Comparison: 6-Item Sleep Problems Index: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.000195% CI: [-14.8, -4.99]Mixed Models Analysis
Comparison: 6-Item Sleep Problems Index: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.008995% CI: [-11.42, -1.67]Mixed Models Analysis
Comparison: 6-Item Sleep Problems Index: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.174695% CI: [-8.21, 1.51]Mixed Models Analysis
Comparison: 9-Item Sleep Problems Index: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-14.96, -5.32]Mixed Models Analysis
Comparison: 9-Item Sleep Problems Index: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.035995% CI: [-9.91, -0.34]Mixed Models Analysis
Comparison: 9-Item Sleep Problems Index: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.039595% CI: [-9.78, -0.24]Mixed Models Analysis
Comparison: Optimal Sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.027895% CI: [0.02, 0.27]Mixed Models Analysis
Comparison: Optimal Sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.295% CI: [-0.04, 0.2]Mixed Models Analysis
Comparison: Optimal Sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.339695% CI: [-0.06, 0.18]Mixed Models Analysis
Comparison: Sleep Disturbance: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-20.93, -8.19]Mixed Models Analysis
Comparison: Sleep Disturbance: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.058495% CI: [-12.43, 0.22]Mixed Models Analysis
Comparison: Sleep Disturbance: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.00995% CI: [-14.76, -2.15]Mixed Models Analysis
Comparison: Snoring: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.240595% CI: [-7.2, 1.82]Mixed Models Analysis
Comparison: Snoring: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.756595% CI: [-5.18, 3.77]Mixed Models Analysis
Comparison: Snoring: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.379295% CI: [-6.43, 2.47]Mixed Models Analysis
Secondary
Minutes of Stage N1, N2, N3 and R Sleep
Minutes of Stage 1 Non-Rapid Eye Movement (Non-REM) sleep (Stage N1), Stage 2 Non-REM sleep (Stage N2), Stage 3 Non-REM sleep (Stage N3) or Slow Wave Sleep (SWS) and Stage REM (Stage R) sleep, as determined by PSG were calculated as total number of Stage N1 30-second (30-sec) epochs divided by 2, total number of Stage N2 30-sec epochs divided by 2, total number of Stage N3 30-sec epochs divided by 2 and total number of Stage R 30-sec epochs divided by 2 respectively. Arithmetic mean of minutes of stage N1, N2, N3 and R sleep of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Pregabalin 300 mg | Minutes of Stage N1, N2, N3 and R Sleep | Stage N1 Sleep | 38.06 minutes |
| Pregabalin 300 mg | Minutes of Stage N1, N2, N3 and R Sleep | Stage R Sleep | 70.40 minutes |
| Pregabalin 300 mg | Minutes of Stage N1, N2, N3 and R Sleep | Stage N3 Sleep/SWS | 66.88 minutes |
| Pregabalin 300 mg | Minutes of Stage N1, N2, N3 and R Sleep | Stage N2 Sleep | 227.05 minutes |
| Pramipexole 0.5 mg | Minutes of Stage N1, N2, N3 and R Sleep | Stage N2 Sleep | 241.52 minutes |
| Pramipexole 0.5 mg | Minutes of Stage N1, N2, N3 and R Sleep | Stage N3 Sleep/SWS | 34.78 minutes |
| Pramipexole 0.5 mg | Minutes of Stage N1, N2, N3 and R Sleep | Stage N1 Sleep | 48.38 minutes |
| Pramipexole 0.5 mg | Minutes of Stage N1, N2, N3 and R Sleep | Stage R Sleep | 51.80 minutes |
| Placebo | Minutes of Stage N1, N2, N3 and R Sleep | Stage N2 Sleep | 204.35 minutes |
| Placebo | Minutes of Stage N1, N2, N3 and R Sleep | Stage N1 Sleep | 43.72 minutes |
| Placebo | Minutes of Stage N1, N2, N3 and R Sleep | Stage R Sleep | 75.37 minutes |
| Placebo | Minutes of Stage N1, N2, N3 and R Sleep | Stage N3 Sleep/SWS | 45.95 minutes |
Comparison: Stage N1 sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.007695% CI: [-9.8, -1.54]Mixed Models Analysis
Comparison: Stage N1 sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-14.43, -6.21]Mixed Models Analysis
Comparison: Stage N1 sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.025795% CI: [0.58, 8.73]Mixed Models Analysis
Comparison: Stage N2 sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.000395% CI: [10.74, 34.67]Mixed Models Analysis
Comparison: Stage N2 sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.017495% CI: [-26.35, -2.59]Mixed Models Analysis
Comparison: Stage N2 sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [25.38, 48.96]Mixed Models Analysis
Comparison: Stage N3 sleep/SWS: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [12.61, 29.25]Mixed Models Analysis
Comparison: Stage N3 sleep/SWS: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [23.83, 40.36]Mixed Models Analysis
Comparison: Stage N3 sleep/SWS: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.00895% CI: [-19.37, -2.97]Mixed Models Analysis
Comparison: Stage R sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.083495% CI: [-10.61, 0.67]Mixed Models Analysis
Comparison: Stage R sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [12.99, 24.19]Mixed Models Analysis
Comparison: Stage R sleep: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-29.12, -18.01]Mixed Models Analysis
Secondary
Number of Arousals (NASO)
NASO, as determined by PSG, was calculated as number of times there is a shift from a stage N2 to N3 or R 30-sec epoch to a stage N1 30-sec epoch from the onset of persistent sleep to light on. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NASO of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Number of Arousals (NASO) | 17.84 arousals |
| Pramipexole 0.5 mg | Number of Arousals (NASO) | 24.19 arousals |
| Placebo | Number of Arousals (NASO) | 20.29 arousals |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.061795% CI: [-5.02, 0.12]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-8.91, -3.8]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.002895% CI: [1.37, 6.44]Mixed Models Analysis
Secondary
Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1)
NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage 2 Non-REM \[Stage N2\] 30-second (30-sec) epoch, Stage 3 Non-REM \[Stage N3\] 30-sec epoch, or stage rapid eye movement \[stage R\] 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | 18.43 awakenings |
| Pramipexole 0.5 mg | Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | 26.30 awakenings |
| Placebo | Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) | 21.10 awakenings |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.007795% CI: [-4.63, -0.72]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-9.81, -5.93]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [3.27, 7.12]Mixed Models Analysis
Secondary
Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2)
NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30-sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2) | 7.68 awakenings |
| Pramipexole 0.5 mg | Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2) | 12.39 awakenings |
| Placebo | Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2) | 10.55 awakenings |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-3.93, -1.8]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-5.76, -3.65]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.000795% CI: [0.79, 2.89]Mixed Models Analysis
Secondary
Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) Scale
CGI-I: 7-point clinician rated scale to assess improvement in disease condition as compared to the start of the study medication (baseline), ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved). Higher score = more affected.
Time frame: Baseline, Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin 300 mg | Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) Scale | 61.2 percentage of participants |
| Pramipexole 0.5 mg | Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) Scale | 50.0 percentage of participants |
| Placebo | Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) Scale | 33.3 percentage of participants |
Secondary
Periodic Limb Movement Arousal Index (PLMAI)
PLMAI, as determined by PSG was number of periodic limb movements leading to arousal per hour (per hour of Total Sleep Time \[TST\]). Arithmetic mean of PLMAI of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least one post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Periodic Limb Movement Arousal Index (PLMAI) | 3.93 movement/hour |
| Pramipexole 0.5 mg | Periodic Limb Movement Arousal Index (PLMAI) | 2.66 movement/hour |
| Placebo | Periodic Limb Movement Arousal Index (PLMAI) | 7.61 movement/hour |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-5.44, -1.92]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.154195% CI: [-0.48, 3.01]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-6.68, -3.21]Mixed Models Analysis
Secondary
Periodic Limb Movement Index (PLMI)
PLMI, as determined by PSG was number of periodic limb movements per hour based on time in bed (TIB). Arithmetic mean of PLMI of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Periodic Limb Movement Index (PLMI) | 25.45 movement/hour |
| Pramipexole 0.5 mg | Periodic Limb Movement Index (PLMI) | 14.11 movement/hour |
| Placebo | Periodic Limb Movement Index (PLMI) | 39.95 movement/hour |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-20.26, -8.74]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.000195% CI: [5.65, 17.04]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-31.51, -20.17]Mixed Models Analysis
Secondary
Periodic Limb Movement in Sleep Index (PLMSI)
PLMSI, as determined by PSG was number of periodic limb movements in sleep per hour based on TST. Arithmetic mean of PLMSI of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Periodic Limb Movement in Sleep Index (PLMSI) | 22.42 movement/hour |
| Pramipexole 0.5 mg | Periodic Limb Movement in Sleep Index (PLMSI) | 8.00 movement/hour |
| Placebo | Periodic Limb Movement in Sleep Index (PLMSI) | 36.95 movement/hour |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-20.84, -8.22]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [8.18, 20.67]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-35.16, -22.74]Mixed Models Analysis
Secondary
Restless Legs Syndrome-Next Day Impact (RLS-NDI)
RLS-NDI:participant-rated instrument to assess daytime performance and participant's previous night's sleep, consists of 14 items encompassing 5 domains:tiredness;emotional functioning;social functioning;cognitive functioning;activities of daily living and 1 global item for overall well-being. Each item: 0-10 scale; 0=Not at all; 10=Extremely. Total score: sum of scores from question 1-14 (question 10, 11: scores reversed). Total score range: 0-140; higher scores: more severe impact. Arithmetic mean of RLS-NDI of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 3 and Week 5 of Each Intervention Period or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Restless Legs Syndrome-Next Day Impact (RLS-NDI) | 41.43 units on a scale |
| Pramipexole 0.5 mg | Restless Legs Syndrome-Next Day Impact (RLS-NDI) | 46.33 units on a scale |
| Placebo | Restless Legs Syndrome-Next Day Impact (RLS-NDI) | 46.78 units on a scale |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.039695% CI: [-10.44, -0.26]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.056895% CI: [-9.95, 0.14]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.858995% CI: [-5.44, 4.54]Mixed Models Analysis
Secondary
Restless Leg Syndrome - Quality of Life Scale (RLS-QoL)
RLS-QoL: psychometrically and clinically valid and reliable participant-rated instrument, assesses impact of RLS on participant quality of life. Specifically, it assessed effects of RLS on health status function (symptom severity, daily activity, social functioning, sleep, concentrating and decision making, travelling, sexual activity, and work) giving a summary score ranging from 0-100. Higher scores reflect better quality of life. Recall period: 1 week prior to assessment. Arithmetic mean of RLS-QoL score of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Restless Leg Syndrome - Quality of Life Scale (RLS-QoL) | 73.30 units on a scale |
| Pramipexole 0.5 mg | Restless Leg Syndrome - Quality of Life Scale (RLS-QoL) | 70.05 units on a scale |
| Placebo | Restless Leg Syndrome - Quality of Life Scale (RLS-QoL) | 68.03 units on a scale |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.001995% CI: [1.98, 8.55]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.050695% CI: [-0.01, 6.51]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.222295% CI: [-1.24, 5.26]Mixed Models Analysis
Secondary
Sleep Efficiency (SE)
SE, as determined by PSG, was the TST divided by the time in bed (TIB)(both in minutes), multiplied by 100. Sum of 2 consecutive days of recording divided by 2 at the end of each intervention period. Arithmetic mean of SE of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Sleep Efficiency (SE) | 83.81 Percentage of time asleep |
| Pramipexole 0.5 mg | Sleep Efficiency (SE) | 78.58 Percentage of time asleep |
| Placebo | Sleep Efficiency (SE) | 77.02 Percentage of time asleep |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [4.57, 9.02]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [3.02, 7.45]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.162295% CI: [-0.64, 3.75]Mixed Models Analysis
Secondary
Subjective Sleep Questionnaire (SSQ): Latency Subscale
SSQ: participant-rated instrument assesses sleep behavior; measures sleep quantity, quality. Comprised of 5 items giving 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. Latency (time to fall asleep \[in minutes\]): numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0 - 840 minutes, lower value: better sleep. Arithmetic mean of subscale score of each participant for all periods was taken prior to employing linear mixed model. Hours of sleep subscale results reported as sTST.
Time frame: Week 3 and Week 5 of each intervention period or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Latency Subscale | 42.49 minutes |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Latency Subscale | 40.59 minutes |
| Placebo | Subjective Sleep Questionnaire (SSQ): Latency Subscale | 50.07 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.021595% CI: [-14.03, -1.14]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.556995% CI: [-4.49, 8.29]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.003695% CI: [-15.81, -3.16]Mixed Models Analysis
Secondary
Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale
SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items giving 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This (1 item) subscale: numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0 awakenings to 30 awakenings. Lower value indicates better quality of sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.
Time frame: Week 3 and Week 5 of Each Intervention Period or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale | 1.69 awakenings |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale | 2.64 awakenings |
| Placebo | Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale | 2.51 awakenings |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-1.18, -0.47]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-1.31, -0.6]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.467795% CI: [-0.22, 0.48]Mixed Models Analysis
Secondary
Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale
SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This 1 item subscale: numerical rating completed by participant 30 minutes after waking; recall period: night before, Range: 0 to 100, higher score: better quality of sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.
Time frame: Week 3 and Week 5 of each intervention period or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale | 6.74 units on a scale |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale | 5.69 units on a scale |
| Placebo | Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale | 5.70 units on a scale |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [0.63, 1.45]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [0.65, 1.46]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.940395% CI: [-0.42, 0.39]Mixed Models Analysis
Secondary
Subjective Sleep Questionnaire (SSQ): Total Wake Time After Sleep Onset Subscale
SSQ: participant-rated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This 1 item subscale (in minutes): numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0-1440 minutes. Lower value: better sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.
Time frame: Week 3 and Week 5 of each intervention period or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Total Wake Time After Sleep Onset Subscale | 53.78 minutes |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Total Wake Time After Sleep Onset Subscale | 82.23 minutes |
| Placebo | Subjective Sleep Questionnaire (SSQ): Total Wake Time After Sleep Onset Subscale | 79.09 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-35.83, -14.8]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-38.89, -18.02]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.546195% CI: [-7.13, 13.4]Mixed Models Analysis
Secondary
Subjective Total Sleep Time (sTST)
sTST as derived from Subjective Sleep Questionnaire (SSQ), a participant reported subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. Completed by the participant 30 minutes after waking; recall period is the night before. Arithmetic mean of sTST of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 3 and Week 5 of Each Intervention Period or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Subjective Total Sleep Time (sTST) | 400.97 minutes |
| Pramipexole 0.5 mg | Subjective Total Sleep Time (sTST) | 374.19 minutes |
| Placebo | Subjective Total Sleep Time (sTST) | 370.16 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [16.14, 45.49]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.000495% CI: [12.26, 41.32]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.580795% CI: [-10.36, 18.41]Mixed Models Analysis
Secondary
Total Sleep Time (TST)
TST, as determined by PSG, was the number of non-wake (30-sec) epochs from the beginning of recording to the end of the recording. TST was the sum of 2 consecutive days of recording divided by 2 at the end of each intervention period. Arithmetic mean of TST of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Total Sleep Time (TST) | 402.38 minutes |
| Pramipexole 0.5 mg | Total Sleep Time (TST) | 376.52 minutes |
| Placebo | Total Sleep Time (TST) | 369.66 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [22.02, 43.42]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [15.22, 36.49]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.200595% CI: [-3.69, 17.42]Mixed Models Analysis
Secondary
Wake Time After Sleep (WTAS)
WTAS, as determined by PSG, was the number of wake (30-sec) epochs after the final awakening until the end of the 8-hour recording. WTAS was the sum of 2 consecutive days of recordings divided by 2 at the end of each intervention period. Arithmetic mean of WTAS of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Wake Time After Sleep (WTAS) | 5.58 minutes |
| Pramipexole 0.5 mg | Wake Time After Sleep (WTAS) | 7.86 minutes |
| Placebo | Wake Time After Sleep (WTAS) | 8.88 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.0895% CI: [-7, 0.4]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.220995% CI: [-5.95, 1.39]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.581595% CI: [-4.66, 2.63]Mixed Models Analysis
Secondary
Wake Time During Sleep (WTDS)
WTDS, as determined by PSG, was the number of wake (30-sec) epochs after the onset of persistent sleep and prior to the final awakening or at the end of 8-hour recording. WTDS was the sum of 2 consecutive days of recordings divided by 2 at the end of each intervention period. Arithmetic mean of WTDS of each participant for all periods was taken prior to employing linear mixed model.
Time frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET
Population: ITT population included set of randomized participants who had at least 1 dose of study medication and had at least 1 post-randomization efficacy assessment. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin 300 mg | Wake Time During Sleep (WTDS) | 45.77 minutes |
| Pramipexole 0.5 mg | Wake Time During Sleep (WTDS) | 70.51 minutes |
| Placebo | Wake Time During Sleep (WTDS) | 69.75 minutes |
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-32.78, -15.18]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: <0.000195% CI: [-33.46, -16.02]Mixed Models Analysis
Comparison: P-value was calculated using linear mixed model analysis with treatment, period and sequence as fixed effects. Random effects were participant within sequence and residual error. The LS means and SE were used to test for a treatment difference and construct 2-sided 95% CIs. The hypothesis test was 2-sided and conducted at the 5% level of significance.p-value: 0.862295% CI: [-7.9, 9.43]Mixed Models Analysis