Dose-Response and Pharmacokinetics of Gabapentin Enacarbil (GEn [XP13512 / GSK1838262]) in Restless Legs Syndrome (XP081)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
XenoPort, Inc.
ClinicalTrials.gov Identifier:
NCT01332305
First received: April 7, 2011
Last updated: July 15, 2013
Last verified: May 2011
  Purpose

The objective of the study was to generate the data necessary to determine the gabapentin exposure produced by 4 dose levels of GEn (600 mg, 1200 mg, 1800 mg, and 2400 mg) or placebo, and the corresponding relief of symptoms in subjects with Restless Legs Syndrome (RLS).


Condition Intervention Phase
Restless Legs Syndrome
Drug: GEn (XP13512/GSK1838262)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Study to Assess the Efficacy, Safety, and Pharmacokinetics of XP13512 (GSK1838262) in Patients With Restless Legs Syndrome

Resource links provided by NLM:


Further study details as provided by XenoPort, Inc.:

Primary Outcome Measures:
  • Mean Css, Max and Css, Min [ Time Frame: Weeks 4 and 12 ] [ Designated as safety issue: No ]
    Css, max is defined as the maximum or "peak" concentration of a drug observed after multiple administration, at steady state. Css, max is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. Css, min is defined as the minimum concentration of a drug observed after its administration, in steady state. ng, nanograms; PK, pharmacokinetic; W, week; BLQ, below limit of quantitation.

  • Mean Tmax and T1/2 [ Time Frame: Weeks 4 and 12 ] [ Designated as safety issue: No ]
    Tmax is defined as the time to the maximum or "peak" concentration of a drug observed after multiple administration. T1/2 is defined as the time to when half of the total amount of a particular substance is eliminated from the body.

  • Mean AUCss [ Time Frame: Weeks 4 and 12 ] [ Designated as safety issue: No ]
    The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUCss is the area under the curve during the steady-state period. The AUCss is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUCss used concentration data from 0 to 24 hours at steady-state for Weeks 4 and 12.


Enrollment: 217
Study Start Date: January 2007
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GEn (XP13512/GSK1838262) 600 mg
GEn (XP13512/GSK1838262) 600 mg
Drug: GEn (XP13512/GSK1838262)
Double-Blind Treatment Phase: 600 mg GEn (XP13512) orally, once daily for 3 days followed by 600 or 1200 mg on days 4-6, followed by 600 or 1200 or 1800 mg on days 7-9, followed by 600 or 1200 or 1800 or 2400 mg on days 10-84. Double-Blind Taper Phase: 600 or 1200 or 1800 mg GEn (XP13512) orally, once daily on days 85-86, followed by 600 mg or 1200 mg on days 87-88, followed by 600 mg on days 89-91
Other Names:
  • XP13512
  • GSK1838262
Experimental: GEn (XP13512/GSK1838262) 1200 mg
GEn (XP13512/GSK1838262) 1200 mg
Drug: GEn (XP13512/GSK1838262)
Double-Blind Treatment Phase: 600 mg GEn (XP13512) orally, once daily for 3 days followed by 600 or 1200 mg on days 4-6, followed by 600 or 1200 or 1800 mg on days 7-9, followed by 600 or 1200 or 1800 or 2400 mg on days 10-84. Double-Blind Taper Phase: 600 or 1200 or 1800 mg GEn (XP13512) orally, once daily on days 85-86, followed by 600 mg or 1200 mg on days 87-88, followed by 600 mg on days 89-91
Other Names:
  • XP13512
  • GSK1838262
Experimental: GEn (XP13512/GSK1838262) 1800 mg
GEn (XP13512/GSK1838262) 1800 mg
Drug: GEn (XP13512/GSK1838262)
Double-Blind Treatment Phase: 600 mg GEn (XP13512) orally, once daily for 3 days followed by 600 or 1200 mg on days 4-6, followed by 600 or 1200 or 1800 mg on days 7-9, followed by 600 or 1200 or 1800 or 2400 mg on days 10-84. Double-Blind Taper Phase: 600 or 1200 or 1800 mg GEn (XP13512) orally, once daily on days 85-86, followed by 600 mg or 1200 mg on days 87-88, followed by 600 mg on days 89-91
Other Names:
  • XP13512
  • GSK1838262
Experimental: GEn (XP13512/GSK1838262) 2400 mg
GEn (XP13512/GSK1838262) 2400 mg
Drug: GEn (XP13512/GSK1838262)
Double-Blind Treatment Phase: 600 mg GEn (XP13512) orally, once daily for 3 days followed by 600 or 1200 mg on days 4-6, followed by 600 or 1200 or 1800 mg on days 7-9, followed by 600 or 1200 or 1800 or 2400 mg on days 10-84. Double-Blind Taper Phase: 600 or 1200 or 1800 mg GEn (XP13512) orally, once daily on days 85-86, followed by 600 mg or 1200 mg on days 87-88, followed by 600 mg on days 89-91
Other Names:
  • XP13512
  • GSK1838262
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo orally once daily

Detailed Description:

This was a multicenter, randomized, double blind, placebo controlled, parallel group study, comparing 4 doses of GEn (XP13512) with placebo given once daily to subjects with RLS. Eligible subjects were randomized in equal numbers into 1 of 5 treatment groups (GEn 600 mg, 1200 mg, 1800 mg, or 2400 mg or placebo) for 12 weeks of treatment. Data from this study will be utilized as part of a larger pharmacokinetic (PK) pharmacodynamic (PD) analysis of data from several studies (XP084/RXP111495) that are part of the GEn RLS clinical development program. Safety and tolerability were also assessed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women at least 18 years of age
  • RLS, based on the IRLSSG Diagnostic Criteria
  • History of RLS symptoms occurring at least 15 nights in the month prior to Screening or, if on RLS treatment, this frequency of symptoms must have been applicable prior to start of treatment
  • Documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights
  • Total RLS severity score of 15 or greater on the IRLS Rating Scale
  • If taking dopamine agonists, gabapentin, or other treatments for RLS (e.g., opioids, benzodiazepines) medications must have been discontinued at least 2 weeks prior to Screening;
  • 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;
  • Body Mass Index (BMI) of 34 or below
  • estimated creatinine clearance of at least 60 mL/min

Exclusion Criteria:

  • a sleep disorder (e.g., sleep apnea) that may significantly 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 (e.g., diabetic neuropathy, Parkinson's disease, multiple sclerosis, dyskinesias, and dystonias);
  • other clinically significant or unstable medical condition or conditions which could affect RLS treatment efficacy assessments
  • serum ferritin level below 20 ng/mL
  • currently suffering from moderate or severe depression using the Diagnostic and Statistical Manual of Mental Disorders and Treatment IV (DSM IV TR)
  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: NCT01332305

Locations
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75213
Sponsors and Collaborators
XenoPort, Inc.
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by XenoPort, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: XenoPort, Inc.
ClinicalTrials.gov Identifier: NCT01332305     History of Changes
Other Study ID Numbers: 111462
Study First Received: April 7, 2011
Results First Received: April 28, 2011
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Restless Legs Syndrome
Psychomotor Agitation
Nervous System Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Parasomnias
Mental Disorders
Dyskinesias
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on August 18, 2014