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

NCT01668667 | Completed Phase 4 Results

• 1 other identifier: 114025
• Study Type: interventional
• Target: 501
• Locations: 1 country
• Sites: 42

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).

Conditions

Restless Legs Syndrome

Keywords

gabapentin enacarbil; Horizant

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• The Dose-response Relationship of Change From Baseline in IRLS Rating Scale Total Score at End of Treatment

  Baseline, 12 Weeks

• The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment

  12 Weeks

Study Arms (4)

GSK1838262 600 mg

ACTIVE COMPARATOR

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

Drug: GSK1838262 600 mg

GSK1838262 450 mg

ACTIVE COMPARATOR

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

Drug: GSK1838262 450 mg

GSK1838262 300 mg

ACTIVE COMPARATOR

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

Drug: GSK1838262 300 mg

GSK1838262 placebo match

PLACEBO COMPARATOR

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

Drug: GSK1838262 Placebo match

Interventions

GSK1838262 600 mg DRUG

Drug: GSK1838262 600 mg/day Comparison of 3 doses

Also known as: Horizant, gabapentin enacarbil GEn, XP13512

GSK1838262 600 mg

GSK1838262 450 mg DRUG

Drug: GSK1838262 450 mg/day Comparison of 3 doses

Also known as: Horizant, gabapentin enacarbil GEn, XP13512

GSK1838262 450 mg

GSK1838262 300 mg DRUG

Drug: GSK1838262 300 mg/day Comparison of 3 doses

Also known as: Horizant, gabapentin enacarbil GEn, XP13512

GSK1838262 300 mg

GSK1838262 Placebo match DRUG

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

GSK1838262 placebo match

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• XenoPort, Inc.: lead

Study Sites (42)

GSK Investigational Site

Phoenix, Arizona, 85020, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85050, United States

Location

GSK Investigational Site

Tucson, Arizona, 85704, United States

Location

GSK Investigational Site

Little Rock, Arkansas, 72211, United States

Location

GSK Investigational Site

Santa Monica, California, 90404, United States

Location

GSK Investigational Site

Colorado Springs, Colorado, 80907, United States

Location

GSK Investigational Site

Denver, Colorado, 80239, United States

Location

GSK Investigational Site

DeLand, Florida, 32720, United States

Location

GSK Investigational Site

Tampa, Florida, 33609, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30342, United States

Location

GSK Investigational Site

Woodstock, Georgia, 30189, United States

Location

GSK Investigational Site

Lenexa, Kansas, 66214, United States

Location

GSK Investigational Site

Topeka, Kansas, 66606, United States

Location

GSK Investigational Site

Crestview Hills, Kentucky, 41017, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40217, United States

Location

GSK Investigational Site

Metairie, Louisiana, 70006, United States

Location

GSK Investigational Site

Chevy Chase, Maryland, 20815, United States

Location

GSK Investigational Site

Bingham Farms, Michigan, 48025, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68134, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89119, United States

Location

GSK Investigational Site

Albuquerque, New Mexico, 87106, United States

Location

GSK Investigational Site

Hickory, North Carolina, 28601, United States

Location

GSK Investigational Site

Raleigh, North Carolina, 27612, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45255, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44130, United States

Location

GSK Investigational Site

Middleburg Heights, Ohio, 44130, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73112, United States

Location

GSK Investigational Site

Duncansville, Pennsylvania, 16635, United States

Location

GSK Investigational Site

Lafayette Hill, Pennsylvania, 19444, United States

Location

GSK Investigational Site

Warwick, Rhode Island, 02886, United States

Location

GSK Investigational Site

Columbia, South Carolina, 29201, United States

Location

GSK Investigational Site

Greer, South Carolina, 29651, United States

Location

GSK Investigational Site

Mt. Pleasant, South Carolina, 29464, United States

Location

GSK Investigational Site

Jackson, Tennessee, 38305, United States

Location

GSK Investigational Site

Austin, Texas, 78731, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76135, United States

Location

GSK Investigational Site

San Angelo, Texas, 76904, United States

Location

GSK Investigational Site

San Antonio, Texas, 78205, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Murray, Utah, 84123, United States

Location

GSK Investigational Site

Charlottesville, Virginia, 22911, United States

Location

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

Gabapentin; 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: XenoPort Call Center
• Organization: XenoPort, Inc.

877-936-6778

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: August 20, 2012
• Study Start: June 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: May 24, 2021
• Results First Posted: November 17, 2014

Record last verified: 2021-04

Locations

US (42)