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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01668667
Recruitment Status : Completed
First Posted : August 20, 2012
Results First Posted : November 17, 2014
Last Update Posted : December 2, 2014
Sponsor:
Information provided by (Responsible Party):
XenoPort, Inc.

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).

Condition or disease Intervention/treatment Phase
Restless Legs Syndrome Drug: GSK1838262 600 mg Drug: GSK1838262 450 mg Drug: GSK1838262 300 mg Drug: GSK1838262 Placebo match Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 501 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 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 the Treatment of Subjects With Moderate-to-Severe Primary Restless Legs Syndrome (RLS)
Study Start Date : June 2012
Actual Primary Completion Date : November 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Restless Legs

Arm Intervention/treatment
Active Comparator: GSK1838262 600 mg
Once-daily dose with food in the evening at approximately 5 PM
Drug: GSK1838262 600 mg
Drug: GSK1838262 600 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512

Active Comparator: GSK1838262 450 mg
Once-daily dose with food in the evening at approximately 5 PM
Drug: GSK1838262 450 mg
Drug: GSK1838262 450 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512

Active Comparator: GSK1838262 300 mg
Once-daily dose with food in the evening at approximately 5 PM
Drug: GSK1838262 300 mg
Drug: GSK1838262 300 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512

Placebo Comparator: GSK1838262 placebo match
Once-daily dose with food in the evening at approximately 5 PM
Drug: GSK1838262 Placebo match
Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses




Primary Outcome Measures :
  1. The Change From Baseline to the End of Treatment in the International Restless Legs Syndrome (IRLS) Rating Scale Score [ Time Frame: Baseline, 12 weeks ]

    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.


  2. 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 ]
    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.


Secondary Outcome Measures :
  1. The Dose-response Relationship of Change From Baseline in IRLS Rating Scale Total Score at End of Treatment [ Time Frame: Baseline, 12 Weeks ]

    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.


  2. The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment [ Time Frame: 12 Weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01668667


Locations
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United States, Arizona
GSK Investigational Site
Phoenix, Arizona, United States, 85020
GSK Investigational Site
Phoenix, Arizona, United States, 85050
GSK Investigational Site
Tucson, Arizona, United States, 85704
United States, Arkansas
GSK Investigational Site
Little Rock, Arkansas, United States, 72211
United States, California
GSK Investigational Site
Santa Monica, California, United States, 90404
United States, Colorado
GSK Investigational Site
Colorado Springs, Colorado, United States, 80907
GSK Investigational Site
Denver, Colorado, United States, 80239
United States, Florida
GSK Investigational Site
DeLand, Florida, United States, 32720
GSK Investigational Site
Tampa, Florida, United States, 33609
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30342
GSK Investigational Site
Woodstock, Georgia, United States, 30189
United States, Kansas
GSK Investigational Site
Lenexa, Kansas, United States, 66214
GSK Investigational Site
Topeka, Kansas, United States, 66606
United States, Kentucky
GSK Investigational Site
Crestview Hills, Kentucky, United States, 41017
GSK Investigational Site
Loiuisville, Kentucky, United States, 40217
United States, Louisiana
GSK Investigational Site
Metairie, Louisiana, United States, 70006
United States, Maryland
GSK Investigational Site
Chevy Chase, Maryland, United States, 20815
United States, Michigan
GSK Investigational Site
Bingham Farms, Michigan, United States, 48025
United States, Nebraska
GSK Investigational Site
Omaha, Nebraska, United States, 68134
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89119
United States, New Mexico
GSK Investigational Site
Albuquerque, New Mexico, United States, 87106
United States, North Carolina
GSK Investigational Site
Hickory, North Carolina, United States, 28601
GSK Investigational Site
Raleigh, North Carolina, United States, 27612
GSK Investigational Site
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45255
GSK Investigational Site
Cleveland, Ohio, United States, 44130
GSK Investigational Site
Middleburg Heights, Ohio, United States, 44130
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
GSK Investigational Site
Duncansville, Pennsylvania, United States, 16635
GSK Investigational Site
Lafayette Hill, Pennsylvania, United States, 19444
United States, Rhode Island
GSK Investigational Site
Warwick, Rhode Island, United States, 02886
United States, South Carolina
GSK Investigational Site
Columbia, South Carolina, United States, 29201
GSK Investigational Site
Greer, South Carolina, United States, 29651
GSK Investigational Site
Mount Pleasant, South Carolina, United States, 29464
United States, Tennessee
GSK Investigational Site
Jackson, Tennessee, United States, 38305
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78731
GSK Investigational Site
Fort Worth, Texas, United States, 76135
GSK Investigational Site
San Angelo, Texas, United States, 76904
GSK Investigational Site
San Antonio, Texas, United States, 78205
GSK Investigational Site
San Antonio, Texas, United States, 78229
United States, Utah
GSK Investigational Site
Murray, Utah, United States, 84123
United States, Virginia
GSK Investigational Site
Charlottesville, Virginia, United States, 22911
Sponsors and Collaborators
XenoPort, Inc.
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

Layout table for additonal information
Responsible Party: XenoPort, Inc.
ClinicalTrials.gov Identifier: NCT01668667    
Other Study ID Numbers: 114025
First Posted: August 20, 2012    Key Record Dates
Results First Posted: November 17, 2014
Last Update Posted: December 2, 2014
Last Verified: November 2014
Keywords provided by XenoPort, Inc.:
gabapentin enacarbil
Horizant
Additional relevant MeSH terms:
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Psychomotor Agitation
Restless Legs Syndrome
Syndrome
Disease
Pathologic Processes
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Parasomnias
Mental Disorders
Gabapentin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action