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

Restless Legs Syndrome Clinical Trial

— XP081  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01332305
• Other study ID #: 111462
• Status: Completed
• Phase: Phase 2
• First received: April 7, 2011
• Last updated: July 15, 2013
• Start date: January 2007
• Est. completion date: January 2008

Study information

• Verified date: May 2011
• Source: XenoPort, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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)

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychomotor Agitation
• Restless Legs Syndrome
• Syndrome

Intervention

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
• Placebo
Placebo orally once daily

Locations

Country	Name	City	State
United States	GSK Investigational Site	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
XenoPort, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Css, Max and Css, Min	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.	Weeks 4 and 12	No
Primary	Mean Tmax and T1/2	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.	Weeks 4 and 12	No
Primary	Mean AUCss	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.	Weeks 4 and 12	No