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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
XenoPort, Inc.
ClinicalTrials.gov Identifier:
NCT01668667
First received: June 14, 2012
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Restless Legs Syndrome
Drug: GSK1838262 600 mg
Drug: GSK1838262 450 mg
Drug: GSK1838262 300 mg
Drug: GSK1838262 Placebo match
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by XenoPort, Inc.:

Primary Outcome Measures:
  • • The change from Baseline to the end of treatment in the International Restless Legs Syndrome (IRLS) Rating Scale score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    RLS: Subject-rated instrument to assess RLS symptom severity and impact on daily living; 10 items yielding 1 global (total) score. Global score: calculated from all 10 items. Global score range: 0-40. Lower scores reflect lower severity and better quality of life. Change from baseline = score at observation minus score at baseline.

  • • 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 498
Study Start Date: June 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: GSK1838262 600 mg
Drug: GSK1838262 600 mg dose/day
Drug: GSK1838262 600 mg
Drug: GSK1838262 600 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512
Drug: GSK1838262 Placebo match
Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses
Active Comparator: GSK1838262 450 mg
Drug; GSK1838262 450 mg dose/day
Drug: GSK1838262 450 mg
Drug: GSK1838262 450 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512
Drug: GSK1838262 Placebo match
Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses
Active Comparator: GSK1838262 300 mg
Drug: GSK1838262 300 mg dose/day
Drug: GSK1838262 300 mg
Drug: GSK1838262 300 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512
Drug: GSK1838262 Placebo match
Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses
Placebo Comparator: GSK1838262 placebo match
Drug: GSK1838262 matching placebo
Drug: GSK1838262 600 mg
Drug: GSK1838262 600 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512
Drug: GSK1838262 450 mg
Drug: GSK1838262 450 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512
Drug: GSK1838262 300 mg
Drug: GSK1838262 300 mg/day Comparison of 3 doses
Other Names:
  • Horizant
  • gabapentin enacarbil GEn
  • XP13512

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01668667

  Show 42 Study Locations
Sponsors and Collaborators
XenoPort, Inc.
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: XenoPort, Inc.
ClinicalTrials.gov Identifier: NCT01668667     History of Changes
Other Study ID Numbers: 114025
Study First Received: June 14, 2012
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by XenoPort, Inc.:
gabapentin enacarbil
Horizant

Additional relevant MeSH terms:
Psychomotor Agitation
Restless Legs Syndrome
Syndrome
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Parasomnias
Mental Disorders
Disease
Pathologic Processes
Gabapentin
Gamma-Aminobutyric Acid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Antiparkinson Agents
Anti-Dyskinesia Agents
Calcium Channel Blockers
Membrane Transport Modulators

ClinicalTrials.gov processed this record on September 16, 2014