Lyrica Dose Response Study With Restless Legs Syndrome (RLS) Patients

Study Overview
=================
Brief Summary
-----------------
To test the effectiveness and tolerability of Lyrica at various dose levels in RLS patients

Official Title
-----------------
Randomized, Double-Blind, 6-Week Study Of Pregabalin In Subjects With Restless Legs Syndrome

Conditions
-----------------
Restless Legs Syndrome

Intervention / Treatment
-----------------
* Drug: placebo
* Drug: Pregabalin
* Drug: Pregabalin
* Drug: Pregabalin
* Drug: Pregabalin
* Drug: Pregabalin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Moderate to severe idiopathic RLS symptoms occur predominantly in the evening symptoms interfere with sleep onset or maintenance Exclusion Criteria: Any secondary RLS require treatment for daytime RLS symptoms symptomatic neuropathies

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo | Drug: placebo<br>* Placebo control (capsule), once a day, 1- 3 hours before bedtime for 6 weeks<br>* Other names: Sugar pill;|
| Experimental: 2<br>investigational treatment | Drug: Pregabalin<br>* 50 mg (capsule) per day, 1 - 3 hours before bedtime for 6 weeks<br>* Other names: Lyrica, PD 0144723; CI-1008;|
| Experimental: 3<br>investigational treatment | Drug: Pregabalin<br>* 100 mg (capsule) per day, 1 - 3 hours before bedtime for 6 weeks<br>* Other names: Lyrica, PD 0144723; CI-1008;|
| Experimental: 4<br>investigational treatment | Drug: Pregabalin<br>* 150 mg (capsule) per day, 1 - 3 hours before bedtime for 6 weeks<br>* Other names: Lyrica, PD 0144723; CI-1008;|
| Experimental: 5<br>investigational treatment | Drug: Pregabalin<br>* 300 mg (capsule) per day, 1 - 3 hours before bedtime for 6 weeks<br>* Other names: Lyrica, PD 0144723; CI-1008;|
| Experimental: 6<br>investigational treatment | Drug: Pregabalin<br>* 450 mg (capsule) per day, 1 - 3 hours before bedtime for 6 weeks<br>* Other names: Lyrica, PD 0144723; CI-1008;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Restless Leg Syndrome (RLS) International Restless Leg Group Symptom Severity Rating Scale (IRLS) Total Score at Week 6 | IRLS: Subject-rated instrument to assess RLS symptom severity and impact on daily living; 10 items yielding 2 subscale scores and 1 global (total) score. Subscale scores: symptom severity (6 items) and impact on daily living (3 items), with item 5 (daytime somnolence due to RLS) loaded equally on both subscales. Global score: calculated from all 10 items. Subscale score ranges: symptom severity 0-24, impact of daily living 0-12; global score range: 0-40. Lower scores reflect lower severity and better quality of life. Change from baseline = score at observation minus score at baseline. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Responding to Treatment as Assessed by the Clinical Global Impression - Improvement Scale (CGI-I) | Clinical Global Impression - Improvement Scale (CGI-I): 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. Number of subjects responding to treatment at Week 6 with respect to dose level. CGI-I Responders = subjects who reported CGI-I scores of very much improved or much improved. | Week 6 | 
| Number of Subjects With Categorical Scores on the Clinical Global Impression - Severity Scale (CGI-S) | CGI-S Scale: 7-point clinician rated scale to assess severity of subject's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. | Baseline, Week 1, Week 2, Week 4, Week 6, Last Observation Carried Forward (LOCF) | 
| Subjective Sleep Questionnaire (SSQ): Latency Subscale; Observed Change From Baseline | Subjective Sleep Questionnaire (SSQ): subject-rated instrument used to assess sleep behavior; measures sleep quantity and quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, and quality of sleep. Latency subscale (time to fall asleep [in minutes]): numerical rating completed by the subject 30 minutes after waking; recall period is the night before. Lower score reflects greater ease (shorter time) in falling asleep. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 | 
| Subjective Sleep Questionnaire: Hours of Sleep Subscale; Observed Change From Baseline | Subjective Sleep Questionnaire (SSQ): subject-rated instrument used to assess sleep behavior; measures sleep quantity and quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, and quality of sleep. Hours of sleep subscale reflects change in hours of sleep from baseline. Numerical rating completed by the subject 30 minutes after waking; recall period is the night before. | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 | 
| Subjective Sleep Questionnaire: Number of Awakenings Subscale; Observed Change From Baseline | Subjective Sleep Questionnaire (SSQ): subject-rated instrument used to assess sleep behavior; measures sleep quantity and quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, and quality of sleep. Number of awakenings subscale: numerical rating completed by the subject 30 minutes after waking; recall period is the night before. Fewer awakenings reflect better quality of sleep. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 | 
| Subjective Sleep Questionnaire: Total Wake Time After Sleep Onset Subscale; Observed Change From Baseline | Subjective Sleep Questionnaire (SSQ): subject-rated instrument used to assess sleep behavior; measures sleep quantity and quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, and quality of sleep. Total wake time after sleep onset subscale (in minutes): numerical rating completed by the subject 30 minutes after waking; recall period is the night before. Reduction = improvement. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 | 
| Subjective Sleep Questionnaire: Quality of Sleep Subscale; Observed Change From Baseline | Subjective Sleep Questionnaire (SSQ): subject-rated instrument used to assess sleep behavior; measures sleep quantity and quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, and quality of sleep. Quality of sleep subscale: visual analog scale ranging from 1 (very poor) to 100 (excellent) completed by the subject 30 minutes after waking; recall period is the night before. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): Sleep Disturbance Subscale; Observed Change From Baseline | MOS-SS: subject-rated instrument used to assess the key constructs of sleep quantity and quality over the past week; comprised of 12 items yielding 7 subscale scores and 2 composite index scores. Sleep Disturbance Subscale score (4 items): range 0-100; lower score indicates less disturbance. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 4, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): Snoring Subscale; Observed Change From Baseline | MOS-SS: subject-rated instrument used to assess the key constructs of sleep; assesses sleep quantity and quality over the past week. Comprised of 12 items yielding 7 subscale scores and 2 composite index scores. Snoring Subscale score (1 item): range 0-100, lower score indicates less snoring. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 4, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): Awaken Short of Breath or With Headache Subscale; Observed Change From Baseline | MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week ; comprised of 12 items yielding 7 subscale scores and 2 composite index scores. Awaken Short of Breath or with Headache subscale score range: 0-100; lower score indicates less difficulty. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 4, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): Sleep Adequacy Subscale; Observed Change From Baseline | MOS-SS: subject-rated instrument used to assess the key constructs of sleep; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Sleep Adequacy Subscale score range: 0-100; higher scores indicates greater sleep adequacy. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 4, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): Somnolence Subscale; Observed Change From Baseline | MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Sleep Somnolence Subscale score range: 0-100; higher score indicates less somnolence. Change from baseline = score at observation minus score at baseline. | Baseline,, Week 1, Week 2, Week 4, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): Sleep Quantity Subscale; Observed Change From Baseline | MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Sleep Quantity (1 item) subscale score range: 0-24 hours. Change from Baseline in number of hours slept. Change from baseline = score at observation minus score at baseline. | Baseline,, Week 1, Week 2, Week 4, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): 6-Item Sleep Problems Index; Observed Change From Baseline | MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Sleep Problems Index I (6 items): composite index score range 0-100; lower score indicates fewer sleep problems. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 4, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): 9-Item Sleep Problems Index; Observed Change From Baseline | MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Composite index scores are sleep problems Index I (6 items) and sleep problems Index II (9 items). 9-Item Sleep Problems Index range: 0-100; lower score indicates fewer sleep problems. Change from baseline = score at observation minus score at baseline. | Baseline, Week 1, Week 2, Week 4, Week 6 | 
| Medical Outcomes Study - Sleep Scale (MOSS-SS): Optimal Sleep; Observed Cases Summarized by Week | MOS-SS: subject-rated instrument used to assess the key constructs of sleep over the past week; assesses sleep quantity and quality and is comprised 12 items yielding 7 subscale scores and 2 composite index scores. Optimal Sleep subscale is derived from sleep quantity average hours of sleep each night during the past week. Number of subjects with response: YES (Optimal) if sleep quantity was 7 or 8 hours of sleep per night. | Week 1, Week 2, Week 4, Week 6 | 
| Restless Leg Syndrome - Quality of Life Scale (RLS-QoL): Change From Baseline to Week 6 | RLS QoL: subject-rated instrument used to assess the impact of RLS on quality of life and health status function (symptom severity, daily activity, social functioning, sleep, concentrating and decision making, traveling, sexual activity, and work) yielding a summary score ranging from 0-100. Higher scores reflect better quality of life. Recall period is the month prior to the assessment. Change from baseline = score at observation minus score at baseline. | Baseline, Week 6 | 
| Medical Outcomes Study Short Form 36 (SF-36): Change From Baseline to Week 6 | Subject-rated measure of health status comprised of 36 items: 8 subscale scores (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), 2 summary scores (physical component and mental component), and a self-evaluated change in health status. Subscale and summary scores range: 0-100. Higher subscale and summary scores = better health status. Recall period: month prior to the assessment. Change from baseline = score at observation minus score at baseline. | Baseline, Week 6 | 
| Medical Outcomes Study Short Form 36 (SF-36); Number of Subjects With Self-Evaluated Change in Health Status Scores | Subject-rated measure of health status comprised of 36 items: 8 subscale scores (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), 2 summary scores (physical component and mental component), and a self-evaluated change in health status. Self-evaluated change in health status: 5 Likert-type response categories ranging from much worse now to much better now. Recall period: month prior to the assessment. | Baseline, Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pregabalin, RLS, efficacy, safety