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Polysomnography Study Of Pregabalin And Pramipexole Versus Placebo In Patients With Restless Legs Syndrome And Associated Sleep Disturbance

Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00991276
Collaborator
(none)
85
Enrollment
41
Locations
3
Arms
18
Duration (Months)
2.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
85 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled, 3-Way Crossover, Multicenter Polysomnography Study Of Pregabalin And Pramipexole In Adults With Restless Legs Syndrome
Study Start Date :
Dec 1, 2009
Actual Primary Completion Date :
Jun 1, 2011
Actual Study Completion Date :
Jun 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: pregabalin

Drug: pregabalin
capsules; 300 mg once-per-day; 4 weeks of treatment
Other Names:
  • Lyrica

    		•
    Placebo Comparator: placebo

    Drug: placebo
    capsules; 0 mg once-per-day; 4 weeks of treatment
    Active Comparator: pramipexole

    Drug: pramipexole
    capsules; 0.5 mg once-per-day; 4 weeks of treatment
    Other Names:
  • Mirapex

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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.

    20. 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.

    21. 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.

    22. 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.

    23. 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.

    24. 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.

    25. 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.

    26. 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.

    27. 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.

    28. 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.

    29. 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.

    30. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Jasper Alabama United States 35501
    2 Pfizer Investigational Site Phoenix Arizona United States 85037
    3 Pfizer Investigational Site Tucson Arizona United States 85712
    4 Pfizer Investigational Site Little Rock Arkansas United States 72205
    5 Pfizer Investigational Site Little Rock Arkansas United States 72211
    6 Pfizer Investigational Site Burlingame California United States 94010
    7 Pfizer Investigational Site Pasadena California United States 91106
    8 Pfizer Investigational Site Redlands California United States 92373
    9 Pfizer Investigational Site San Diego California United States 92103
    10 Pfizer Investigational Site San Diego California United States 92121
    11 Pfizer Investigational Site Santa Ana California United States 92705
    12 Pfizer Investigational Site Santa Monica California United States 90404
    13 Pfizer Investigational Site Aurora Colorado United States 80012
    14 Pfizer Investigational Site Hallandale Beach Florida United States 33009
    15 Pfizer Investigational Site Miami Florida United States 33143
    16 Pfizer Investigational Site Pembroke Pines Florida United States 33026
    17 Pfizer Investigational Site Spring Hill Florida United States 34609
    18 Pfizer Investigational Site Atlanta Georgia United States 30342
    19 Pfizer Investigational Site Macon Georgia United States 31201
    20 Pfizer Investigational Site Overland Park Kansas United States 66212
    21 Pfizer Investigational Site Crestview Hills Kentucky United States 41017
    22 Pfizer Investigational Site Lexington Kentucky United States 40513
    23 Pfizer Investigational Site Baton Rouge Louisiana United States 70809
    24 Pfizer Investigational Site Chevy Chase Maryland United States 20815
    25 Pfizer Investigational Site Brighton Massachusetts United States 02135
    26 Pfizer Investigational Site Kalamazoo Michigan United States 49048
    27 Pfizer Investigational Site Portage Michigan United States 49024
    28 Pfizer Investigational Site New York New York United States 10019
    29 Pfizer Investigational Site Hickory North Carolina United States 28601
    30 Pfizer Investigational Site Raleigh North Carolina United States 27607
    31 Pfizer Investigational Site Winston-Salem North Carolina United States 27103
    32 Pfizer Investigational Site Cincinnati Ohio United States 45227
    33 Pfizer Investigational Site Dublin Ohio United States 43017
    34 Pfizer Investigational Site Middleburg Heights Ohio United States 44130
    35 Pfizer Investigational Site Oklahoma City Oklahoma United States 73112
    36 Pfizer Investigational Site Clarks Summit Pennsylvania United States 18411
    37 Pfizer Investigational Site Lafayette Hill Pennsylvania United States 19444
    38 Pfizer Investigational Site Columbia South Carolina United States 29201
    39 Pfizer Investigational Site Austin Texas United States 78731
    40 Pfizer Investigational Site Austin Texas United States 78756
    41 Pfizer Investigational Site Dallas Texas United States 75231

    Sponsors and Collaborators

    • Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
    ClinicalTrials.gov Identifier:
    NCT00991276
    Other Study ID Numbers:
    • A0081185
    First Posted:
    Oct 7, 2009
    Last Update Posted:
    Feb 15, 2021
    Last Verified:
    Sep 1, 2012
    Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
    restless legs syndrome RLS polysomnography PSG sleep disturbance patient reported outcome
    Additional relevant MeSH terms:
    Psychomotor Agitation
    Restless Legs Syndrome
    Syndrome
    Pregabalin
    Pramipexole

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo Then Pramipexole 0.5 mg Then Pregabalin 300 mg Pramipexole 0.5 mg Then Pregabalin 300 mg Then Placebo Pregabalin 300 mg Then Placebo Then Pramipexole 0.5 mg Pregabalin 300 mg Then Pramipexole 0.5 mg Then Placebo Placebo Then Pregabalin 300 mg Then Pramipexole 0.5 mg Pramipexole 0.5 mg Then Placebo Then Pregabalin 300 mg
    Arm/Group Description 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. 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. 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. 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. 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. 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.
    Period Title: First Intervention Period
    STARTED 15 13 14 15 15 13
    COMPLETED 15 10 14 11 11 12
    NOT COMPLETED 0 3 0 4 4 1
    Period Title: First Intervention Period
    STARTED 15 10 14 11 11 12
    COMPLETED 15 10 14 11 11 12
    NOT COMPLETED 0 0 0 0 0 0
    Period Title: First Intervention Period
    STARTED 15 10 14 11 11 12
    COMPLETED 14 8 14 9 10 11
    NOT COMPLETED 1 2 0 2 1 1
    Period Title: First Intervention Period
    STARTED 14 8 14 9 10 11
    COMPLETED 14 8 14 9 10 11
    NOT COMPLETED 0 0 0 0 0 0
    Period Title: First Intervention Period
    STARTED 14 8 14 9 10 11
    COMPLETED 13 8 13 8 10 10
    NOT COMPLETED 1 0 1 1 0 1

    Baseline Characteristics

    Arm/Group Title Placebo Then Pramipexole 0.5 mg Then Pregabalin 300 mg Pramipexole 0.5 mg Then Pregabalin 300 mg Then Placebo Pregabalin 300 mg Then Placebo Then Pramipexole 0.5 mg Pregabalin 300 mg Then Pramipexole 0.5 mg Then Placebo Placebo Then Pregabalin 300 mg Then Pramipexole 0.5 mg Pramipexole 0.5 mg Then Placebo Then Pregabalin 300 mg Total
    Arm/Group Description 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. 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. 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. 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. 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. 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. Total of all reporting groups
    Overall Participants 15 13 14 15 15 13 85
    Age, Customized (participants) [Number]
    Less than 18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    18 to 44 years
    3
    20%
    4
    30.8%
    1
    7.1%
    2
    13.3%
    5
    33.3%
    3
    23.1%
    18
    21.2%
    45 to 64 years
    8
    53.3%
    7
    53.8%
    11
    78.6%
    10
    66.7%
    8
    53.3%
    8
    61.5%
    52
    61.2%
    Greater than or equal to 65 years
    4
    26.7%
    2
    15.4%
    2
    14.3%
    3
    20%
    2
    13.3%
    2
    15.4%
    15
    17.6%
    Sex: Female, Male (Count of Participants)
    Female
    11
    73.3%
    7
    53.8%
    8
    57.1%
    9
    60%
    12
    80%
    7
    53.8%
    54
    63.5%
    Male
    4
    26.7%
    6
    46.2%
    6
    42.9%
    6
    40%
    3
    20%
    6
    46.2%
    31
    36.5%

    Outcome Measures

    1. Primary Outcome
    Title Wake After Sleep Onset (WASO)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [minutes]
    51.50
    78.42
    78.60
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was step 1 in a step-down procedure (if p-value < 0.05, then continue to next step) used to control the Type I error rate.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -27.10
    Confidence Interval (2-Sided) 95%
    -35.78 to -18.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.38
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -26.93
    Confidence Interval (2-Sided) 95%
    -35.54 to -18.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.35
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9684
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.17
    Confidence Interval (2-Sided) 95%
    -8.72 to 8.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.32
    Estimation Comments
    2. Secondary Outcome
    Title Periodic Limb Movement Arousal Index (PLMAI)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [movement/hour]
    3.93
    2.66
    7.61
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was step 2 in a step-down procedure (if p-value < 0.05, then continue to next step) used to control the Type I error rate.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -3.68
    Confidence Interval (2-Sided) 95%
    -5.44 to -1.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.89
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1541
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.26
    Confidence Interval (2-Sided) 95%
    -0.48 to 3.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.88
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -4.94
    Confidence Interval (2-Sided) 95%
    -6.68 to -3.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.88
    Estimation Comments
    3. Secondary Outcome
    Title Subjective Total Sleep Time (sTST)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 72 70
    Least Squares Mean (95% Confidence Interval) [minutes]
    400.97
    374.19
    370.16
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was step 3 in a step-down procedure (if p-value < 0.05, then continue to next step) used to control the Type I error rate.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 30.81
    Confidence Interval (2-Sided) 95%
    16.14 to 45.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.42
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 26.79
    Confidence Interval (2-Sided) 95%
    12.26 to 41.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.34
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5807
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 4.03
    Confidence Interval (2-Sided) 95%
    -10.36 to 18.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.27
    Estimation Comments
    4. Secondary Outcome
    Title Minutes of Stage N1, N2, N3 and R Sleep
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Stage N1 Sleep
    38.06
    48.38
    43.72
    Stage N2 Sleep
    227.05
    241.52
    204.35
    Stage N3 Sleep/SWS
    66.88
    34.78
    45.95
    Stage R Sleep
    70.40
    51.80
    75.37
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0076
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -5.67
    Confidence Interval (2-Sided) 95%
    -9.80 to -1.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.09
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -10.32
    Confidence Interval (2-Sided) 95%
    -14.43 to -6.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.08
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0257
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value 4.65
    Confidence Interval (2-Sided) 95%
    0.58 to 8.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.06
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 22.70
    Confidence Interval (2-Sided) 95%
    10.74 to 34.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.05
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0174
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -14.47
    Confidence Interval (2-Sided) 95%
    -26.35 to -2.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.00
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 37.17
    Confidence Interval (2-Sided) 95%
    25.38 to 48.96
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.96
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 20.93
    Confidence Interval (2-Sided) 95%
    12.61 to 29.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.20
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was step 4 in a step-down procedure (if p-value < 0.05, then continue to next step) used to control the Type I error rate.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 32.10
    Confidence Interval (2-Sided) 95%
    23.83 to 40.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.18
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0080
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -11.17
    Confidence Interval (2-Sided) 95%
    -19.37 to -2.97
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.14
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0834
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -4.97
    Confidence Interval (2-Sided) 95%
    -10.61 to 0.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.85
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 18.59
    Confidence Interval (2-Sided) 95%
    12.99 to 24.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.83
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -23.56
    Confidence Interval (2-Sided) 95%
    -29.12 to -18.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.81
    Estimation Comments
    5. Secondary Outcome
    Title Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [awakenings]
    18.43
    26.30
    21.10
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0077
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -2.67
    Confidence Interval (2-Sided) 95%
    -4.63 to -0.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.99
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was step 5 in a step-down procedure (if p-value < 0.05, then continue to next step) used to control the Type I error rate.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -7.87
    Confidence Interval (2-Sided) 95%
    -9.81 to -5.93
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.98
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 5.20
    Confidence Interval (2-Sided) 95%
    3.27 to 7.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.97
    Estimation Comments
    6. Secondary Outcome
    Title Restless Legs Syndrome-Next Day Impact (RLS-NDI)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 72 70
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    41.43
    46.33
    46.78
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0396
    Comments This analysis was step 6 in a step-down procedure (if p-value < 0.05, then continue to next step) used to control the Type I error rate.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -5.35
    Confidence Interval (2-Sided) 95%
    -10.44 to -0.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.57
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0568
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -4.90
    Confidence Interval (2-Sided) 95%
    -9.95 to 0.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.55
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8589
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.45
    Confidence Interval (2-Sided) 95%
    -5.44 to 4.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.52
    Estimation Comments
    7. Secondary Outcome
    Title Periodic Limb Movement Index (PLMI)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [movement/hour]
    25.45
    14.11
    39.95
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -14.50
    Confidence Interval (2-Sided) 95%
    -20.26 to -8.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.91
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 11.35
    Confidence Interval (2-Sided) 95%
    5.65 to 17.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.88
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -25.84
    Confidence Interval (2-Sided) 95%
    -31.51 to -20.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.86
    Estimation Comments
    8. Secondary Outcome
    Title Periodic Limb Movement in Sleep Index (PLMSI)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [movement/hour]
    22.42
    8.00
    36.95
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -14.53
    Confidence Interval (2-Sided) 95%
    -20.84 to -8.22
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.19
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 14.42
    Confidence Interval (2-Sided) 95%
    8.18 to 20.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.15
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -28.95
    Confidence Interval (2-Sided) 95%
    -35.16 to -22.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.14
    Estimation Comments
    9. Secondary Outcome
    Title Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [awakenings]
    7.68
    12.39
    10.55
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -2.86
    Confidence Interval (2-Sided) 95%
    -3.93 to -1.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.54
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -4.71
    Confidence Interval (2-Sided) 95%
    -5.76 to -3.65
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0007
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.84
    Confidence Interval (2-Sided) 95%
    0.79 to 2.89
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments
    10. Secondary Outcome
    Title Number of Arousals (NASO)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [arousals]
    17.84
    24.19
    20.29
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0617
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -2.45
    Confidence Interval (2-Sided) 95%
    -5.02 to 0.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.30
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -6.35
    Confidence Interval (2-Sided) 95%
    -8.91 to -3.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.29
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0028
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 3.90
    Confidence Interval (2-Sided) 95%
    1.37 to 6.44
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.28
    Estimation Comments
    11. Secondary Outcome
    Title Arousal Index (NASOI)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [arousals/hour]
    2.75
    4.18
    3.44
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0056
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.69
    Confidence Interval (2-Sided) 95%
    -1.17 to -0.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.42
    Confidence Interval (2-Sided) 95%
    -1.90 to -0.95
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0026
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.74
    Confidence Interval (2-Sided) 95%
    0.26 to 1.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    12. Secondary Outcome
    Title International Restless Legs Syndrome Study Group Rating Scale (IRLS)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 68 70 69
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    12.28
    15.35
    18.38
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -6.10
    Confidence Interval (2-Sided) 95%
    -8.10 to -4.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.01
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0029
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -3.07
    Confidence Interval (2-Sided) 95%
    -5.07 to -1.07
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.01
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0032
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -3.03
    Confidence Interval (2-Sided) 95%
    -5.02 to -1.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.01
    Estimation Comments
    13. Secondary Outcome
    Title Percentage of Participants With Response to Clinical Global Impression - Improvement (CGI-I) Scale
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 70 69
    Number [percentage of participants]
    61.2
    408%
    50.0
    384.6%
    33.3
    237.9%
    14. Secondary Outcome
    Title Latency to Stage R Sleep (LREM)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [minutes]
    95.22
    130.99
    84.52
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1677
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 10.69
    Confidence Interval (2-Sided) 95%
    -4.56 to 25.95
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.71
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -35.77
    Confidence Interval (2-Sided) 95%
    -50.88 to -20.66
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.63
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 46.47
    Confidence Interval (2-Sided) 95%
    31.45 to 61.48
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.59
    Estimation Comments
    15. Secondary Outcome
    Title Latency to Persistent Sleep (LPS)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [minutes]
    31.13
    31.52
    38.86
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1040
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -7.73
    Confidence Interval (2-Sided) 95%
    -17.07 to 1.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.72
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9325
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -9.67 to 8.87
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.68
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1175
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -7.33
    Confidence Interval (2-Sided) 95%
    -16.54 to 1.87
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.65
    Estimation Comments
    16. Secondary Outcome
    Title Wake Time During Sleep (WTDS)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [minutes]
    45.77
    70.51
    69.75
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -23.98
    Confidence Interval (2-Sided) 95%
    -32.78 to -15.18
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.45
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -24.74
    Confidence Interval (2-Sided) 95%
    -33.46 to -16.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.41
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8622
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.76
    Confidence Interval (2-Sided) 95%
    -7.90 to 9.43
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.38
    Estimation Comments
    17. Secondary Outcome
    Title Wake Time After Sleep (WTAS)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [minutes]
    5.58
    7.86
    8.88
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0800
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -3.30
    Confidence Interval (2-Sided) 95%
    -7.00 to 0.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.87
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2209
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -2.28
    Confidence Interval (2-Sided) 95%
    -5.95 to 1.39
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.86
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5815
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.02
    Confidence Interval (2-Sided) 95%
    -4.66 to 2.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.84
    Estimation Comments
    18. Secondary Outcome
    Title Total Sleep Time (TST)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [minutes]
    402.38
    376.52
    369.66
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 32.72
    Confidence Interval (2-Sided) 95%
    22.02 to 43.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.41
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 25.86
    Confidence Interval (2-Sided) 95%
    15.22 to 36.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.37
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2005
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 6.86
    Confidence Interval (2-Sided) 95%
    -3.69 to 17.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.33
    Estimation Comments
    19. Secondary Outcome
    Title Sleep Efficiency (SE)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Least Squares Mean (95% Confidence Interval) [Percentage of time asleep]
    83.81
    78.58
    77.02
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 6.80
    Confidence Interval (2-Sided) 95%
    4.57 to 9.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.12
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 5.24
    Confidence Interval (2-Sided) 95%
    3.02 to 7.45
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.12
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1622
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.56
    Confidence Interval (2-Sided) 95%
    -0.64 to 3.75
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.11
    Estimation Comments
    20. Secondary Outcome
    Title Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 73 76 72
    Hour 1 (n= 66, 67, 66)
    1.62
    (4.12)
    2.26
    (2.69)
    3.35
    (3.84)
    Hour 2 (n= 67, 70, 66)
    5.04
    (6.15)
    7.07
    (5.48)
    7.39
    (6.85)
    Hour 3 (n= 67, 70, 67)
    4.89
    8.23
    8.90
    Hour 4 (n= 67, 70, 68)
    6.21
    11.54
    9.52
    Hour 5 (n= 67, 70, 68)
    5.93
    10.39
    10.04
    Hour 6 (n= 67, 71, 68)
    5.78
    10.54
    10.52
    Hour 7 (n= 67, 71, 68)
    9.18
    11.44
    12.09
    Hour 8 (n= 67, 71, 68)
    13.16
    18.27
    18.15
    Quarter 1 (n= 67, 70, 66)
    6.42
    8.99
    10.35
    Quarter 2 (n= 67, 70, 68)
    11.08
    19.77
    18.18
    Quarter 3 (n= 67, 71, 68)
    11.81
    20.77
    20.55
    Quarter 4 (n= 67, 71, 68)
    22.37
    29.55
    30.21
    21. Secondary Outcome
    Title Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 73 76 72
    Hour 1 (n= 66, 67, 66)
    0.70
    (0.90)
    1.39
    (1.12)
    1.10
    (0.76)
    Hour 2 (n= 67, 70, 66)
    2.06
    (1.41)
    3.32
    (1.74)
    2.47
    (1.44)
    Hour 3 (n= 67, 70, 67)
    2.09
    3.42
    2.66
    Hour 4 (n= 67, 70, 68)
    2.44
    3.83
    2.71
    Hour 5 (n= 67, 70, 68)
    2.47
    3.76
    2.87
    Hour 6 (n= 67, 71, 68)
    2.91
    3.68
    3.16
    Hour 7 (n= 67, 71, 68)
    3.07
    4.04
    3.32
    Hour 8 (n= 67, 71, 68)
    2.76
    3.46
    3.11
    Quarter 1 (n= 67, 70, 66)
    2.71
    4.61
    3.49
    Quarter 2 (n= 67, 70, 68)
    4.53
    7.27
    5.32
    Quarter 3 (n= 67, 71, 68)
    5.39
    7.37
    6.04
    Quarter 4 (n= 67, 71, 68)
    5.87
    7.36
    6.44
    22. Secondary Outcome
    Title Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 73 76 72
    Hour 1 (n= 66, 67, 66)
    0.42
    (0.60)
    0.61
    (0.71)
    0.73
    (0.59)
    Hour 2 (n= 67, 70, 66)
    1.04
    (0.83)
    1.72
    (1.13)
    1.37
    (1.06)
    Hour 3 (n= 67, 70, 67)
    0.99
    1.71
    1.41
    Hour 4 (n= 67, 70, 68)
    1.01
    1.84
    1.48
    Hour 5 (n= 67, 70, 68)
    1.06
    1.76
    1.48
    Hour 6 (n= 67, 71, 68)
    1.02
    1.57
    1.44
    Hour 7 (n= 67, 71, 68)
    1.24
    1.94
    1.57
    Hour 8 (n= 67, 71, 68)
    1.00
    1.56
    1.28
    Quarter 1 (n= 67, 70, 66)
    1.43
    2.27
    2.06
    Quarter 2 (n= 67, 70, 68)
    1.99
    3.56
    2.85
    Quarter 3 (n= 67, 71, 68)
    2.10
    3.30
    2.92
    Quarter 4 (n= 67, 71, 68)
    2.25
    3.44
    2.86
    23. Secondary Outcome
    Title Hourly and Quarterly Assessment of Number of Arousals (NASO)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 73 76 72
    Hour 1 (n= 66, 67, 66)
    1.48
    (1.65)
    2.06
    (2.22)
    1.79
    (1.78)
    Hour 2 (n= 67, 70, 66)
    2.36
    (2.03)
    3.23
    (2.15)
    2.68
    (1.99)
    Hour 3 (n= 67, 70, 67)
    2.31
    3.23
    2.80
    Hour 4 (n= 67, 70, 68)
    2.94
    3.41
    2.76
    Hour 5 (n= 67, 70, 68)
    2.33
    3.20
    2.89
    Hour 6 (n= 67, 71, 68)
    2.39
    3.30
    2.70
    Hour 7 (n= 67, 71, 68)
    2.15
    3.28
    2.66
    Hour 8 (n= 67, 71, 68)
    2.07
    2.98
    2.46
    Quarter 1 (n= 67, 70, 66)
    3.75
    5.09
    4.26
    Quarter 2 (n= 67, 70, 68)
    5.25
    6.67
    5.55
    Quarter 3 (n= 67, 71, 68)
    4.75
    6.44
    5.61
    Quarter 4 (n= 67, 71, 68)
    4.23
    6.24
    5.13
    24. Secondary Outcome
    Title Hourly and Quarterly Assessment of Periodic Limb Movement (PLM)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Hour 1
    31.45
    (29.70)
    21.57
    (27.03)
    54.67
    (39.98)
    Hour 2
    26.38
    (29.20)
    12.49
    (14.51)
    52.93
    (40.92)
    Hour 3
    40.93
    14.05
    48.76
    Hour 4
    30.35
    14.50
    46.58
    Hour 5
    25.70
    11.93
    36.17
    Hour 6
    21.02
    10.57
    32.47
    Hour 7
    14.22
    11.11
    27.04
    Hour 8
    13.37
    16.55
    20.97
    Quarter 1
    57.82
    34.02
    107.56
    Quarter 2
    71.29
    28.55
    95.31
    Quarter 3
    46.77
    22.49
    68.66
    Quarter 4
    27.60
    27.64
    48.01
    25. Secondary Outcome
    Title Hourly and Quarterly Assessment of Sleep Efficiency (SE)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 71 68
    Hour 1
    62.31
    (24.14)
    66.88
    (24.30)
    57.80
    (22.90)
    Hour 2
    86.13
    (16.94)
    83.43
    (16.03)
    77.31
    (20.49)
    Hour 3
    90.22
    84.86
    81.86
    Hour 4
    89.41
    79.84
    82.61
    Hour 5
    90.00
    81.85
    82.92
    Hour 6
    90.33
    81.64
    82.49
    Hour 7
    84.70
    80.90
    79.86
    Hour 8
    78.07
    69.51
    69.75
    Quarter 1
    74.21
    75.15
    67.62
    Quarter 2
    89.84
    82.37
    82.30
    Quarter 3
    90.09
    81.74
    82.75
    Quarter 4
    81.37
    75.16
    74.84
    26. Secondary Outcome
    Title Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily in any intervention period.
    Measure Participants 67 72 70
    Least Squares Mean (95% Confidence Interval) [awakenings]
    1.69
    2.64
    2.51
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.83
    Confidence Interval (2-Sided) 95%
    -1.18 to -0.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.18
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.96
    Confidence Interval (2-Sided) 95%
    -1.31 to -0.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.18
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4677
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.13
    Confidence Interval (2-Sided) 95%
    -0.22 to 0.48
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.18
    Estimation Comments
    27. Secondary Outcome
    Title Subjective Sleep Questionnaire (SSQ): Total Wake Time After Sleep Onset Subscale
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 65 71 70
    Least Squares Mean (95% Confidence Interval) [minutes]
    53.78
    82.23
    79.09
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -25.32
    Confidence Interval (2-Sided) 95%
    -35.83 to -14.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.31
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -28.45
    Confidence Interval (2-Sided) 95%
    -38.89 to -18.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.27
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5461
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 3.14
    Confidence Interval (2-Sided) 95%
    -7.13 to 13.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.19
    Estimation Comments
    28. Secondary Outcome
    Title Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 72 70
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    6.74
    5.69
    5.70
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.63 to 1.45
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.21
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.05
    Confidence Interval (2-Sided) 95%
    0.65 to 1.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.20
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9403
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -0.42 to 0.39
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.20
    Estimation Comments
    29. Secondary Outcome
    Title Subjective Sleep Questionnaire (SSQ): Latency Subscale
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 67 72 70
    Least Squares Mean (95% Confidence Interval) [minutes]
    42.49
    40.59
    50.07
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0215
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -7.58
    Confidence Interval (2-Sided) 95%
    -14.03 to -1.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.26
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5569
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 1.90
    Confidence Interval (2-Sided) 95%
    -4.49 to 8.29
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.23
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0036
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -9.48
    Confidence Interval (2-Sided) 95%
    -15.81 to -3.16
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.20
    Estimation Comments
    30. Secondary Outcome
    Title Medical Outcomes Study - Sleep Scale (MOS-SS)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 73 76 72
    Awaken Short of Breath/with Headache (n= 68,71,69)
    11.59
    13.10
    10.88
    Adequacy (n= 68,71,69)
    54.96
    43.90
    40.79
    Somnolence (n= 68,71,69)
    21.28
    21.32
    23.71
    Sleep Quantity (n= 68,71,69)
    6.43
    6.50
    5.97
    6-Item Sleep Problems Index (n= 68,71,69)
    30.69
    37.24
    40.59
    9-Item Sleep Problems Index (n= 68,71,69)
    32.75
    37.88
    42.89
    Optimal Sleep (n= 68,71,69)
    0.43
    0.35
    0.29
    Sleep Disturbance (n= 68,71,69)
    34.08
    40.19
    48.65
    Snoring (n= 67,71,68)
    15.27
    15.97
    17.96
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.6947
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.71
    Confidence Interval (2-Sided) 95%
    -2.85 to 4.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.80
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3980
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.52
    Confidence Interval (2-Sided) 95%
    -5.06 to 2.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.79
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2144
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 2.23
    Confidence Interval (2-Sided) 95%
    -1.30 to 5.76
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.78
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0006
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 14.17
    Confidence Interval (2-Sided) 95%
    6.25 to 22.08
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.00
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0061
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 11.07
    Confidence Interval (2-Sided) 95%
    3.22 to 18.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.97
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4342
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 3.10
    Confidence Interval (2-Sided) 95%
    -4.72 to 10.93
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.95
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2420
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -2.43
    Confidence Interval (2-Sided) 95%
    -6.53 to 1.66
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.07
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9810
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.05
    Confidence Interval (2-Sided) 95%
    -4.12 to 4.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.05
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2468
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -2.38
    Confidence Interval (2-Sided) 95%
    -6.44 to 1.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.05
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1496
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.46
    Confidence Interval (2-Sided) 95%
    -0.17 to 1.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.32
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.8184
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.07
    Confidence Interval (2-Sided) 95%
    -0.69 to 0.55
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.31
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0918
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.53
    Confidence Interval (2-Sided) 95%
    -0.09 to 1.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.31
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -9.89
    Confidence Interval (2-Sided) 95%
    -14.80 to -4.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.48
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0089
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -6.54
    Confidence Interval (2-Sided) 95%
    -11.42 to -1.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.46
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1746
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -3.35
    Confidence Interval (2-Sided) 95%
    -8.21 to 1.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.45
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -10.14
    Confidence Interval (2-Sided) 95%
    -14.96 to -5.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.44
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0359
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -5.13
    Confidence Interval (2-Sided) 95%
    -9.91 to -0.34
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.42
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0395
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -5.01
    Confidence Interval (2-Sided) 95%
    -9.78 to -0.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.41
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0278
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.14
    Confidence Interval (2-Sided) 95%
    0.02 to 0.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.06
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2000
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.08
    Confidence Interval () 95%
    -0.04 to 0.20
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.06
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3396
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 0.06
    Confidence Interval (2-Sided) 95%
    -0.06 to 0.18
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.06
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -14.56
    Confidence Interval (2-Sided) 95%
    -20.93 to -8.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.22
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0584
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -6.11
    Confidence Interval (2-Sided) 95%
    -12.43 to 0.22
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.20
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0090
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -8.45
    Confidence Interval (2-Sided) 95%
    -14.76 to -2.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.19
    Estimation Comments
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2405
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -2.69
    Confidence Interval (2-Sided) 95%
    -7.20 to 1.82
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.28
    Estimation Comments
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.7565
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.70
    Confidence Interval (2-Sided) 95%
    -5.18 to 3.77
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.26
    Estimation Comments
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3792
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.98
    Confidence Interval (2-Sided) 95%
    -6.43 to 2.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.25
    Estimation Comments
    31. Secondary Outcome
    Title Restless Leg Syndrome - Quality of Life Scale (RLS-QoL)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. PBO capsule matched to PPX 0.5 mg once daily or PGB 300 mg once daily in any intervention period.
    Measure Participants 68 71 69
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    73.30
    70.05
    68.03
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0019
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 5.27
    Confidence Interval (2-Sided) 95%
    1.98 to 8.55
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.66
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Pregabalin 300 mg, Pramipexole 0.5 mg
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0506
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 3.25
    Confidence Interval (2-Sided) 95%
    -0.01 to 6.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.65
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Pramipexole 0.5 mg, Placebo
    Comments 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.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.2222
    Comments This analysis was not included in the step-down procedure (if p-value < 0.05, then continue to next step) to control Type I error.
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 2.01
    Confidence Interval (2-Sided) 95%
    -1.24 to 5.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.64
    Estimation Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description The same event may appear as both an AE and a SAE. But, distinct events are presented. An event may be categorized as serious in 1 subject; as nonserious in another subject or 1 subject may have experienced both serious, nonserious events in study. 'At risk population'= who received study treatments in different interventions; PGB=75,PPX=76,PBO=73.
    Arm/Group Title Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Arm/Group Description PGB capsule 300 mg once daily in any intervention period. PPX capsule 0.5 mg once daily in any intervention period. 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 any of the intervention period.
    All Cause Mortality
    Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/75 (2.7%) 1/76 (1.3%) 3/73 (4.1%)
    Infections and infestations
    Gastroenteritis 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Investigations
    Blood pressure orthostatic decreased 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Metabolism and nutrition disorders
    Hypokalaemia 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Nervous system disorders
    Dizziness postural 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Psychiatric disorders
    Suicidal ideation 0/75 (0%) 1/76 (1.3%) 1/73 (1.4%)
    Vascular disorders
    Deep vein thrombosis 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Other (Not Including Serious) Adverse Events
    Pregabalin 300 mg Pramipexole 0.5 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 46/75 (61.3%) 40/76 (52.6%) 27/73 (37%)
    Blood and lymphatic system disorders
    Anaemia 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Cardiac disorders
    Ventricular tachycardia 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Ear and labyrinth disorders
    Vertigo 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Eye disorders
    Diplopia 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Dry eye 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Excessive eye blinking 1/75 (1.3%) 0/76 (0%) 1/73 (1.4%)
    Vision blurred 3/75 (4%) 0/76 (0%) 0/73 (0%)
    Gastrointestinal disorders
    Constipation 3/75 (4%) 1/76 (1.3%) 2/73 (2.7%)
    Diarrhoea 0/75 (0%) 1/76 (1.3%) 2/73 (2.7%)
    Dry mouth 4/75 (5.3%) 2/76 (2.6%) 1/73 (1.4%)
    Dyspepsia 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Gastritis 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Gingivitis 1/75 (1.3%) 0/76 (0%) 1/73 (1.4%)
    Haemorrhoidal haemorrhage 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Hypoaesthesia oral 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Nausea 4/75 (5.3%) 6/76 (7.9%) 1/73 (1.4%)
    Toothache 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Vomiting 2/75 (2.7%) 3/76 (3.9%) 0/73 (0%)
    General disorders
    Asthenia 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Chest discomfort 1/75 (1.3%) 0/76 (0%) 1/73 (1.4%)
    Fatigue 1/75 (1.3%) 1/76 (1.3%) 1/73 (1.4%)
    Feeling abnormal 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Feeling drunk 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Gait disturbance 2/75 (2.7%) 0/76 (0%) 0/73 (0%)
    Hangover 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Influenza like illness 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Irritability 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Non-cardiac chest pain 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Oedema 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Oedema peripheral 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Pain 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Pyrexia 0/75 (0%) 2/76 (2.6%) 0/73 (0%)
    Infections and infestations
    Bronchitis 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Gastroenteritis 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Gastroenteritis viral 0/75 (0%) 3/76 (3.9%) 0/73 (0%)
    Influenza 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Nasopharyngitis 1/75 (1.3%) 2/76 (2.6%) 1/73 (1.4%)
    Sinusitis 1/75 (1.3%) 3/76 (3.9%) 2/73 (2.7%)
    Upper respiratory tract infection 4/75 (5.3%) 2/76 (2.6%) 0/73 (0%)
    Urinary tract infection 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Viral upper respiratory tract infection 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Injury, poisoning and procedural complications
    Back injury 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Contusion 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Hand fracture 0/75 (0%) 1/76 (1.3%) 1/73 (1.4%)
    Road traffic accident 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Thermal burn 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Investigations
    Blood creatine phosphokinase increased 2/75 (2.7%) 0/76 (0%) 1/73 (1.4%)
    Blood creatinine increased 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Blood glucose increased 1/75 (1.3%) 1/76 (1.3%) 1/73 (1.4%)
    Blood pressure abnormal 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Red cell distribution width increased 0/75 (0%) 1/76 (1.3%) 1/73 (1.4%)
    Serum ferritin decreased 1/75 (1.3%) 1/76 (1.3%) 2/73 (2.7%)
    Weight increased 3/75 (4%) 1/76 (1.3%) 0/73 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/75 (1.3%) 0/76 (0%) 1/73 (1.4%)
    Hyperglycaemia 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Increased appetite 1/75 (1.3%) 1/76 (1.3%) 1/73 (1.4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Back pain 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Bursitis 1/75 (1.3%) 1/76 (1.3%) 1/73 (1.4%)
    Muscle spasms 1/75 (1.3%) 1/76 (1.3%) 1/73 (1.4%)
    Muscle twitching 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Musculoskeletal pain 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Musculoskeletal stiffness 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Myalgia 0/75 (0%) 1/76 (1.3%) 1/73 (1.4%)
    Neck pain 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Pain in extremity 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Melanocytic naevus 0/75 (0%) 1/76 (1.3%) 1/73 (1.4%)
    Nervous system disorders
    Amnesia 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Balance disorder 3/75 (4%) 0/76 (0%) 0/73 (0%)
    Disturbance in attention 4/75 (5.3%) 0/76 (0%) 0/73 (0%)
    Dizziness 18/75 (24%) 2/76 (2.6%) 1/73 (1.4%)
    Dizziness postural 1/75 (1.3%) 0/76 (0%) 1/73 (1.4%)
    Dysgeusia 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Headache 4/75 (5.3%) 6/76 (7.9%) 5/73 (6.8%)
    Lethargy 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Memory impairment 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Migraine 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Motor dysfunction 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Sedation 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Sinus headache 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Somnolence 13/75 (17.3%) 6/76 (7.9%) 3/73 (4.1%)
    Syncope 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Psychiatric disorders
    Abnormal dreams 2/75 (2.7%) 2/76 (2.6%) 1/73 (1.4%)
    Agitation 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Anxiety 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Daydreaming 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Depression 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Distractibility 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Dysphoria 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Euphoric mood 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Insomnia 0/75 (0%) 1/76 (1.3%) 2/73 (2.7%)
    Libido increased 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Middle insomnia 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Orgasm abnormal 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Restlessness 0/75 (0%) 2/76 (2.6%) 0/73 (0%)
    Renal and urinary disorders
    Nephrolithiasis 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Nocturia 0/75 (0%) 1/76 (1.3%) 0/73 (0%)
    Renal pain 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Urine flow decreased 2/75 (2.7%) 0/76 (0%) 0/73 (0%)
    Reproductive system and breast disorders
    Erectile dysfunction 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Menstruation irregular 1/75 (1.3%) 1/76 (1.3%) 1/73 (1.4%)
    Ovarian cyst 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Pelvic pain 0/75 (0%) 1/76 (1.3%) 1/73 (1.4%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/75 (0%) 2/76 (2.6%) 1/73 (1.4%)
    Cough 0/75 (0%) 2/76 (2.6%) 1/73 (1.4%)
    Nasal congestion 1/75 (1.3%) 2/76 (2.6%) 0/73 (0%)
    Oropharyngeal pain 1/75 (1.3%) 0/76 (0%) 1/73 (1.4%)
    Sinus congestion 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Sleep apnoea syndrome 1/75 (1.3%) 1/76 (1.3%) 1/73 (1.4%)
    Skin and subcutaneous tissue disorders
    Hypoaesthesia facial 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Ingrowing nail 0/75 (0%) 0/76 (0%) 1/73 (1.4%)
    Pruritus 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Surgical and medical procedures
    Endodontic procedure 1/75 (1.3%) 0/76 (0%) 0/73 (0%)
    Sinus operation 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Vascular disorders
    Hypertension 1/75 (1.3%) 1/76 (1.3%) 0/73 (0%)
    Hypotension 0/75 (0%) 1/76 (1.3%) 0/73 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
    ClinicalTrials.gov Identifier:
    NCT00991276
    Other Study ID Numbers:
    • A0081185
    First Posted:
    Oct 7, 2009
    Last Update Posted:
    Feb 15, 2021
    Last Verified:
    Sep 1, 2012