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

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.

Inclusion Criteria:

- Men or women 18 years of age or older

- History of RLS symptoms for at least 15 nights/month

- Documented RLS symptoms, using the 7-day RLS Symptom Record, for at least 4 of the 7
consecutive evenings/nights during the night

- Total RLS severity score of 15 or greater on the International RLS (IRLS) Rating
Scale at Visit 1 and at Visit 2

- Discontinuation of dopamine agonists and/or gabapentin , or other treatments for RLS
(e.g. opioids, benzodiazepines) at least 2 weeks prior to Baseline

- If taking any prescription medication, therapy must have been stabilized for at least
3 months prior to Screening with no anticipated changes for the duration of the study

- Female subjects are eligible if of non-childbearing potential or not lactating, has a
negative pregnancy, and agrees to use a highly effective method for avoiding
pregnancy

- Body mass index of 34 or below

- Estimated creatinine clearance of ≥60 mL/min

- Provides written consent in accordance with all applicable regulatory requirements

Exclusion Criteria:

- History of a sleep disorder that may affect the assessment of RLS

- History of RLS symptom augmentation or end-of-dose rebound with previous dopamine
agonist treatment

- Neurologic disease or movement disorder

- Other medical conditions or drug therapy that could affect RLS efficacy assessments
or may present a safety concern

- Have clinically significant or unstable medical conditions

- Have active suicidal plan/intent or has had active suicidal thoughts in the past 6
months; has a history of suicide attempt