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

Phase 2

Completed

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.

Recruitment & Eligibility

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)

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Mean Css, Max and Css, Min	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	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	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.