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

NCT01332305 | Completed Phase 2 Results

• 1 other identifier: 111462
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 1

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).

Conditions

Restless Legs Syndrome

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Study Arms (5)

GEn (XP13512/GSK1838262) 600 mg

EXPERIMENTAL

GEn (XP13512/GSK1838262) 600 mg

Drug: GEn (XP13512/GSK1838262)

GEn (XP13512/GSK1838262) 1200 mg

EXPERIMENTAL

GEn (XP13512/GSK1838262) 1200 mg

Drug: GEn (XP13512/GSK1838262)

GEn (XP13512/GSK1838262) 1800 mg

EXPERIMENTAL

GEn (XP13512/GSK1838262) 1800 mg

Drug: GEn (XP13512/GSK1838262)

GEn (XP13512/GSK1838262) 2400 mg

EXPERIMENTAL

GEn (XP13512/GSK1838262) 2400 mg

Drug: GEn (XP13512/GSK1838262)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

GEn (XP13512/GSK1838262) DRUG

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

Also known as: XP13512, GSK1838262

GEn (XP13512/GSK1838262) 1200 mg; GEn (XP13512/GSK1838262) 1800 mg; GEn (XP13512/GSK1838262) 2400 mg; GEn (XP13512/GSK1838262) 600 mg

Placebo DRUG

Placebo orally once daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• XenoPort, Inc.: lead

Study Sites (1)

GSK Investigational Site

Dallas, Texas, 75213, United States

Location

Related Publications (4)

• Ahmed M, Hays R, Steven Poceta J, Jaros MJ, Kim R, Shang G. Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials. Clin Ther. 2016 Jul;38(7):1726-1737.e1. doi: 10.1016/j.clinthera.2016.05.008. Epub 2016 Jun 7.

  PMID: 27288210 DERIVED

• Avidan AY, Lee D, Park M, Jaros MJ, Shang G, Kim R. The Effect of Gabapentin Enacarbil on Quality of Life and Mood Outcomes in a Pooled Population of Adult Patients with Moderate-to-Severe Primary Restless Legs Syndrome. CNS Drugs. 2016 Apr;30(4):305-16. doi: 10.1007/s40263-016-0329-4.

  PMID: 27067343 DERIVED

• Ondo WG, Hermanowicz N, Borreguero DG, Jaros MJ, Kim R, Shang G. Effect of prior exposure to dopamine agonists on treatment with gabapentin enacarbil in adults with moderate-to-severe primary restless legs syndrome: pooled analyses from 3 randomized trials. J Clin Mov Disord. 2015 Mar 30;2:9. doi: 10.1186/s40734-015-0018-3. eCollection 2015.

  PMID: 26788345 DERIVED

• 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.

  PMID: 22664749 DERIVED

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Results Point of Contact

• Title: XenoPort Call Center
• Organization: XenoPort, Inc.

877-936-6778

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 11, 2011
• Study Start: January 1, 2007
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: July 22, 2013
• Results First Posted: May 26, 2011

Record last verified: 2011-05

Locations

US (1)