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Dose-Response and Pharmacokinetics of Gabapentin Enacarbil (GEn [XP13512 / GSK1838262]) in Restless Legs Syndrome (XP081)

Primary Purpose

Restless Legs Syndrome

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

GEn (XP13512/GSK1838262)

Placebo

About this trial

This is an interventional treatment trial for Restless Legs Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Arm Label

GEn (XP13512/GSK1838262) 600 mg

GEn (XP13512/GSK1838262) 1200 mg

GEn (XP13512/GSK1838262) 1800 mg

GEn (XP13512/GSK1838262) 2400 mg

Placebo

Arm Description

GEn (XP13512/GSK1838262) 600 mg

GEn (XP13512/GSK1838262) 1200 mg

GEn (XP13512/GSK1838262) 1800 mg

GEn (XP13512/GSK1838262) 2400 mg

Placebo

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01332305

First Posted

April 7, 2011

Last Updated

July 15, 2013

Sponsor

XenoPort, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01332305

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2011

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

January 2008 (Actual)

Study Completion Date

January 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

XenoPort, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Restless Legs Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

217 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GEn (XP13512/GSK1838262) 600 mg

Arm Type

Experimental

Arm Description

GEn (XP13512/GSK1838262) 600 mg

Arm Title

GEn (XP13512/GSK1838262) 1200 mg

Arm Type

Experimental

Arm Description

GEn (XP13512/GSK1838262) 1200 mg

Arm Title

GEn (XP13512/GSK1838262) 1800 mg

Arm Type

Experimental

Arm Description

GEn (XP13512/GSK1838262) 1800 mg

Arm Title

GEn (XP13512/GSK1838262) 2400 mg

Arm Type

Experimental

Arm Description

GEn (XP13512/GSK1838262) 2400 mg

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

GEn (XP13512/GSK1838262)

Other Intervention Name(s)

XP13512, GSK1838262

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo orally once daily

Primary Outcome Measure Information:

Title

Mean Css, Max and Css, Min

Description

Time Frame

Weeks 4 and 12

Title

Mean Tmax and T1/2

Description

Time Frame

Weeks 4 and 12

Title

Mean AUCss

Description

Time Frame

Weeks 4 and 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75213

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

27288210

Citation

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.

Results Reference

derived

PubMed Identifier

27067343

Citation

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.

Results Reference

derived

PubMed Identifier

26788345

Citation

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.

Results Reference

derived

PubMed Identifier

22664749

Citation

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.

Results Reference

derived

Learn more about this trial

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

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