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

Restless Legs Syndrome Clinical Trial

— CONCORD  

Official title:

Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Parallel-Group Study to Compare the Efficacy, Tolerability, and Safety of 3 Doses of Gabapentin Enacarbil (GSK1838262) With Placebo in Treatment of Moderate-to-Severe Primary RLS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01668667
• Other study ID #: 114025
• Status: Completed
• Phase: Phase 4
• Start date: June 2012
• Est. completion date: November 2013

Study information

• Verified date: April 2021
• Source: XenoPort, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gabapentin enacarbil (GEn; GSK1838262; HORIZANT), at a dose of 600 mg/day, is currently approved in the United States for the treatment of adults with moderate-to-severe primary Restless Legs Syndrome (RLS). The aim of this study is to compare the efficacy, tolerability, and safety of GEn at lower doses (450 and 300 mg/day) as well as the already approved dose of 600 mg/day versus placebo for the treatment of subjects with moderate to severe primary RLS. This study is being conducted as a post-marketing commitment (PMC) as a condition of the approval of HORIZANT tablets (NDA 022399).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 501
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Psychomotor Agitation
• Restless Legs Syndrome
• Syndrome

Intervention

Drug:
• GSK1838262 600 mg
Drug: GSK1838262 600 mg/day Comparison of 3 doses
• GSK1838262 450 mg
Drug: GSK1838262 450 mg/day Comparison of 3 doses
• GSK1838262 300 mg
Drug: GSK1838262 300 mg/day Comparison of 3 doses
• GSK1838262 Placebo match
Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses

Locations

Country	Name	City	State
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bingham Farms	Michigan
United States	GSK Investigational Site	Charlottesville	Virginia
United States	GSK Investigational Site	Chevy Chase	Maryland
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	Crestview Hills	Kentucky
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Duncansville	Pennsylvania
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Greer	South Carolina
United States	GSK Investigational Site	Hickory	North Carolina
United States	GSK Investigational Site	Jackson	Tennessee
United States	GSK Investigational Site	Lafayette Hill	Pennsylvania
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lenexa	Kansas
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Metairie	Louisiana
United States	GSK Investigational Site	Middleburg Heights	Ohio
United States	GSK Investigational Site	Mount Pleasant	South Carolina
United States	GSK Investigational Site	Murray	Utah
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	San Angelo	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Santa Monica	California
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Topeka	Kansas
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Warwick	Rhode Island
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
XenoPort, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Change From Baseline to the End of Treatment in the International Restless Legs Syndrome (IRLS) Rating Scale Score	International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.; Change from Baseline = LOCF value at current visit - value at Baseline (the last nonmissing assessment before the first dose of study medication). A negative treatment difference indicates a benefit relative to placebo.; The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate.	Baseline, 12 weeks
Primary	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)	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.	12 weeks
Secondary	The Dose-response Relationship of Change From Baseline in IRLS Rating Scale Total Score at End of Treatment	International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.; This model only includes treatment in the model. Least squares mean is used for analysis.	Baseline, 12 Weeks
Secondary	The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment		12 Weeks