Gabapentin Enacarbil (GSK1838262) Adult Restless Leg Syndrome Post Marketing Commitment Study (CONCORD)

• • The change from Baseline to the end of treatment in the International Restless Legs Syndrome (IRLS) Rating Scale score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  RLS: Subject-rated instrument to assess RLS symptom severity and impact on daily living; 10 items yielding 1 global (total) score. Global score: calculated from all 10 items. 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.
  
  
• • The proportion of subjects at the end of treatment who are responders with either "much improved" or "very much improved" on the investigator-rated Clinical Global Impression of Improvement (CGI-I) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  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), on the scale. Higher score = more affected. Number of subjects responding to treatment at Week 12 with respect to dose level. CGI-I Responders = subjects who reported CGI-I scores of very much improved or much improved.
  
  

This is a Phase IV randomized, double-blind, placebo-controlled, fixed-dose, parallel group study to assess the efficacy, tolerability, and safety of 3 doses of GEn (600, 450, and 300 mg/day) compared with placebo in the treatment of subjects with moderate-to-severe primary RLS.

The study will include 9 visits over approximately 14 weeks for eligible subjects including a 1-week Screening Period, a 12-week Treatment Period, and a 1 week Follow up Period. Screening will occur within 1 week of the first scheduled dose of study medication. The total duration of the study, from the first subject enrolled to the last subject completed will be approximately 2 years.

Eligible subjects (at least 18 years of age) must have:

• a diagnosis of RLS according to the IRLSSG Diagnostic Criteria
• a history of RLS symptoms for at least 15 nights in the prior month or, if on treatment, this frequency of symptoms before treatment was started
• documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights during the Screening Period, and a total RLS severity score of at least 15 on the International Restless Legs Syndrome (IRLS) Rating Scale at the screening and baseline visits

Approximately 498 subjects will be enrolled, randomly assigned to treatment groups, and receive study medication once daily for 12 weeks. Subjects will be randomly assigned to receive 1 of the 4 following treatment groups in a ratio of 1:1:1:1:

• GEn 600 mg/day
• GEn 450 mg/day
• GEn 300 mg/day
• Matching placebo Subjects will be instructed to take their study medication once daily with food in the evening at approximately 5 PM. Each tablet must be swallowed whole and not divided, crushed, or chewed.

Each subject, regardless of treatment assignment, will take 3 tablets of study medication (1 tablet from Bottle A, 1 tablet from Bottle B, and 1 tablet from Bottle C) once daily continuing through the end of the Treatment Period (Week 12). Subjects will return to the study site for a follow-up visit (Visit 9, Week 13) approximately 1 week after the last dose of study medication.

Each subject's participation in the study will be approximately 14 weeks unless they withdraw early from the study. For subjects who complete the study, Visit 9 (which can occur between Day 86 and 92) will be considered their end-of-study visit.