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

NCT ID: NCT01668667

Last Updated: 2021-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 501 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2013-11-30

Brief 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).

Detailed 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.

Conditions

Restless Legs Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GSK1838262 600 mg

Once-daily dose with food in the evening at approximately 5 PM

Group Type: ACTIVE_COMPARATOR

GSK1838262 600 mg

Intervention Type: DRUG

Drug: GSK1838262 600 mg/day Comparison of 3 doses

GSK1838262 450 mg

Once-daily dose with food in the evening at approximately 5 PM

Group Type: ACTIVE_COMPARATOR

GSK1838262 450 mg

Intervention Type: DRUG

Drug: GSK1838262 450 mg/day Comparison of 3 doses

GSK1838262 300 mg

Once-daily dose with food in the evening at approximately 5 PM

Group Type: ACTIVE_COMPARATOR

GSK1838262 300 mg

Intervention Type: DRUG

Drug: GSK1838262 300 mg/day Comparison of 3 doses

GSK1838262 placebo match

Once-daily dose with food in the evening at approximately 5 PM

Group Type: PLACEBO_COMPARATOR

GSK1838262 Placebo match

Intervention Type: DRUG

Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses

Interventions

GSK1838262 600 mg

Drug: GSK1838262 600 mg/day Comparison of 3 doses

Intervention Type: DRUG

GSK1838262 450 mg

Drug: GSK1838262 450 mg/day Comparison of 3 doses

Intervention Type: DRUG

GSK1838262 300 mg

Drug: GSK1838262 300 mg/day Comparison of 3 doses

Intervention Type: DRUG

GSK1838262 Placebo match

Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses

Intervention Type: DRUG

Other Intervention Names

Horizant; gabapentin enacarbil GEn; XP13512; Horizant; gabapentin enacarbil GEn; XP13512; Horizant; gabapentin enacarbil GEn; XP13512

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

XenoPort, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

Little Rock, Arkansas, United States

GSK Investigational Site

Santa Monica, California, United States

GSK Investigational Site

Colorado Springs, Colorado, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

DeLand, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Woodstock, Georgia, United States

GSK Investigational Site

Lenexa, Kansas, United States

GSK Investigational Site

Topeka, Kansas, United States

GSK Investigational Site

Crestview Hills, Kentucky, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Metairie, Louisiana, United States

GSK Investigational Site

Chevy Chase, Maryland, United States

GSK Investigational Site

Bingham Farms, Michigan, United States

GSK Investigational Site

Omaha, Nebraska, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Albuquerque, New Mexico, United States

GSK Investigational Site

Hickory, North Carolina, United States

GSK Investigational Site

Raleigh, North Carolina, United States

GSK Investigational Site

Winston-Salem, North Carolina, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Cleveland, Ohio, United States

GSK Investigational Site

Middleburg Heights, Ohio, United States

GSK Investigational Site

Oklahoma City, Oklahoma, United States

GSK Investigational Site

Duncansville, Pennsylvania, United States

GSK Investigational Site

Lafayette Hill, Pennsylvania, United States

GSK Investigational Site

Warwick, Rhode Island, United States

GSK Investigational Site

Columbia, South Carolina, United States

GSK Investigational Site

Greer, South Carolina, United States

GSK Investigational Site

Mt. Pleasant, South Carolina, United States

GSK Investigational Site

Jackson, Tennessee, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Fort Worth, Texas, 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

Murray, Utah, United States

GSK Investigational Site

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

114025

Identifier Type: -

Identifier Source: org_study_id