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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Double-Blind, Placebo-Controlled, 3-Way Crossover, Multicenter Polysomnography Study Of Pregabalin And Pramipexole In Adults With Restless Legs Syndrome

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.

Detailed Summary:
Sponsor: Pfizer

Current Primary Outcome: Wake After Sleep Onset (WASO) [ 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) ]

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.


Original Primary Outcome: Comparison of Wake After Sleep Onset (WASO) as measured by polysomnography at the end of each treatment period. [ Time Frame: 4 weeks ]

Current Secondary Outcome:

  • Periodic Limb Movement Arousal Index (PLMAI) [ 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 ]
    PLMAI, as determined by PSG was number of periodic limb movements leading to arousal per hour (per hour of Total Sleep Time [TST]). Arithmetic mean of PLMAI of each participant for all periods was taken prior to employing linear mixed model.
  • Subjective Total Sleep Time (sTST) [ Time Frame: Week 3 and Week 5 of Each Intervention Period or ET ]
    sTST as derived from Subjective Sleep Questionnaire (SSQ), a participant reported subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. Completed by the participant 30 minutes after waking; recall period is the night before. Arithmetic mean of sTST of each participant for all periods was taken prior to employing linear mixed model.
  • Minutes of Stage N1, N2, N3 and R Sleep [ 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 ]
    Minutes of Stage 1 Non-Rapid Eye Movement (Non-REM) sleep (Stage N1), Stage 2 Non-REM sleep (Stage N2), Stage 3 Non-REM sleep (Stage N3) or Slow Wave Sleep (SWS) and Stage REM (Stage R) sleep, as determined by PSG were calculated as total number of Stage N1 30-second (30-sec) epochs divided by 2, total number of Stage N2 30-sec epochs divided by 2, total number of Stage N3 30-sec epochs divided by 2 and total number of Stage R 30-sec epochs divided by 2 respectively. Arithmetic mean of minutes of stage N1, N2, N3 and R sleep of each participant for all periods was taken prior to employing linear mixed model.
  • Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) [ 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 ]
    NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage 2 Non-REM [Stage N2] 30-second (30-sec) epoch, Stage 3 Non-REM [Stage N3] 30-sec epoch, or stage rapid eye movement [stage R] 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model.
  • Restless Legs Syndrome-Next Day Impact (RLS-NDI) [ Time Frame: Week 3 and Week 5 of Each Intervention Period or ET ]
    RLS-NDI:participant-rated instrument to assess daytime performance and participant's previous night's sleep, consists of 14 items encompassing 5 domains:tiredness;emotional functioning;social functioning;cognitive functioning;activities of daily living and 1 global item for overall well-being. Each item: 0-10 scale; 0=Not at all; 10=Extremely. Total score: sum of scores from question 1-14 (question 10, 11: scores reversed). Total score range: 0-140; higher scores: more severe impact. Arithmetic mean of RLS-NDI of each participant for all periods was taken prior to employing linear mixed model.
  • Periodic Limb Movement Index (PLMI) [ 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 ]
    PLMI, as determined by PSG was number of periodic limb movements per hour based on time in bed (TIB). Arithmetic mean of PLMI of each participant for all periods was taken prior to employing linear mixed model.
  • Periodic Limb Movement in Sleep Index (PLMSI) [ 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 ]
    PLMSI, as determined by PSG was number of periodic limb movements in sleep per hour based on TST. Arithmetic mean of PLMSI of each participant for all periods was taken prior to employing linear mixed model.
  • Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2) [ 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 ]
    NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30-sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30-sec epoch, Stage N3 30-sec epoch, or Stage R 30-sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model.
  • Number of Arousals (NASO) [ 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 ]
    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

    Original Secondary Outcome:

    • Comparison of Periodic Limb Movement Arousal Index (PLMAI) as measured by polysomnography at the end of each treatment period. [ Time Frame: 4 weeks ]
    • Comparison of Subjective Total Sleep Time (sTST) at the end of each treatment period. [ Time Frame: 4 weeks ]
    • Assessment of sleep related efficacy measures, patient reported outcomes, and safety and tolerability. [ Time Frame: 4 weeks ]


    Information By: Pfizer

    Dates:
    Date Received: October 6, 2009
    Date Started: December 2009
    Date Completion:
    Last Updated: September 6, 2012
    Last Verified: September 2012