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
Overview
- Phase
- Phase 2
- Intervention
- GEn (XP13512/GSK1838262)
- Conditions
- Restless Legs Syndrome
- Sponsor
- XenoPort, Inc.
- Enrollment
- 217
- Locations
- 1
- Primary Endpoint
- Mean Css, Max and Css, Min
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
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).
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.
Investigators
Eligibility 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)
Arms & Interventions
GEn (XP13512/GSK1838262) 600 mg
GEn (XP13512/GSK1838262) 600 mg
Intervention: GEn (XP13512/GSK1838262)
GEn (XP13512/GSK1838262) 1200 mg
GEn (XP13512/GSK1838262) 1200 mg
Intervention: GEn (XP13512/GSK1838262)
GEn (XP13512/GSK1838262) 1800 mg
GEn (XP13512/GSK1838262) 1800 mg
Intervention: GEn (XP13512/GSK1838262)
GEn (XP13512/GSK1838262) 2400 mg
GEn (XP13512/GSK1838262) 2400 mg
Intervention: GEn (XP13512/GSK1838262)
Placebo
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Mean Css, Max and Css, Min
Time Frame: Weeks 4 and 12
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
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
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.