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

April 7, 2011
July 15, 2013
January 2007
January 2008   (final data collection date for primary outcome measure)
  • 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.
pharmacokinetic exposure to gabapentin [ Time Frame: Week 4 and 12 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01332305 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Dose-Response and Pharmacokinetics of Gabapentin Enacarbil (GEn [XP13512 / GSK1838262]) in Restless Legs Syndrome
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

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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Restless Legs Syndrome
  • 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
  • Drug: Placebo
    Placebo orally once daily
  • Experimental: GEn (XP13512/GSK1838262) 600 mg
    GEn (XP13512/GSK1838262) 600 mg
    Intervention: Drug: GEn (XP13512/GSK1838262)
  • Experimental: GEn (XP13512/GSK1838262) 1200 mg
    GEn (XP13512/GSK1838262) 1200 mg
    Intervention: Drug: GEn (XP13512/GSK1838262)
  • Experimental: GEn (XP13512/GSK1838262) 1800 mg
    GEn (XP13512/GSK1838262) 1800 mg
    Intervention: Drug: GEn (XP13512/GSK1838262)
  • Experimental: GEn (XP13512/GSK1838262) 2400 mg
    GEn (XP13512/GSK1838262) 2400 mg
    Intervention: Drug: GEn (XP13512/GSK1838262)
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
Lal R, Ellenbogen A, Chen D, Zomorodi K, Atluri H, Luo W, Tovera J, Hurt J, Bonzo D, Lassauzet ML, Vu A, Cundy KC. A randomized, double-blind, placebo-controlled, dose-response study to assess the pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with restless legs syndrome. Clin Neuropharmacol. 2012 Jul-Aug;35(4):165-73. doi: 10.1097/WNF.0b013e318259eac8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
217
January 2008
January 2008   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01332305
111462
No
XenoPort, Inc.
XenoPort, Inc.
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
XenoPort, Inc.
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP