Clinical trial NCT00748098: Polysomnography Study of GSK1838262 Extended Release Tablets Versus Placebo in RLS and Associated Sleep Disturbance
Official title: Study RXP110908, a Polysomnography Study of GSK1838262 (XP13512) Extended Release Tablets Versus Placebo in the Treatment of Restless Legs Syndrome (RLS) and Associated Sleep Disturbance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Restless Legs Syndrome
Restless Legs Syndrome (RLS)
Keywords: PSG
Restless Legs Syndrome
gabapentin enacarbil
XP13512
GSK1838262
sleep disturbance
RLS
polysomnography
Lead sponsor: XenoPort, Inc.
Sponsor class: INDUSTRY
First posted: 2008-09-08
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of GSK1838262 extended release tablets in the treatment of patients with Restless Legs Syndrome and associated sleep disturbance.

Detailed description: Double-blind, multi-center, placebo-controlled, 2-period crossover study which assessed the efficacy and safety of gabapentin enacarbil (GEn; GSK1838262; XP13512) extended release tablets in adults with Restless Legs Syndrome (RLS)-associated sleep disturbance. One hundred thirty-six (136) adult subjects with RLS-associated sleep disturbance and periodic limb movements (PLM) were randomized from 23 centers in the United States. Subjects who met all eligibility criteria were randomized to receive a treatment sequence of GEn:placebo or placebo:GEn. Investigational product was taken with food at approximately 5pm. Investigational product was dosed as 600mg/day x3 days followed by 1200mg/day x25 days for each 4-week treatment period. There was a 1-week taper at 600mg after each treatment period followed by a 1-week washout between treatments. Polysomnography (PSG) was used to objectively evaluate changes in sleep and PLMs.

Eligibility criteria: Inclusion criteria:

* Provided written informed consent.
* Diagnosed with primary RLS using the International RLS Study Group Diagnostic Criteria with a total score of 15 or greater on the International RLS (IRLS) Rating Scale and significant sleep disturbance indicated on Item 4 of the IRLS rating scale.
* Have history of RLS symptoms at least 15 nights/month.
* Minimum average of 15 Periodic Limb Movements during Sleep per hour (measured using actigraphy).

Exclusion criteria:

* Secondary RLS
* Primary sleep disorder
* Sleep apnea
* Have any medical conditions that may impact efficacy assessments or that may present a safety concern.
* Pregnant or lactating or women of child-bearing potential who are not practicing an acceptable method of birth control.
* Use of any prohibited medication.

Primary outcomes:
measure: Adjusted Mean Change From Baseline in Wake Time During Sleep (WTDS) at Week 4/10 Measured by Polysomnography (PSG) (Sleep Study) Using Last Observation Carried Forward (LOCF)
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
Secondary outcomes:
measure: Adjusted Mean Change From Baseline in Periodic Limb Movements Associated With Arousal (PLMAI) at Week 4/10 as Measured by Polysomnography Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the International Restless Legs Rating Scale (IRLS) Total Score at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Item 4 (Sleep Disturbance) Scores of the IRLS Rating Scale at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in Time Spent in N1 Sleep as Measured by Polysomnography at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Percentage of Total Sleep Time Spent in the N1 Sleep Stage at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in Time Spent in the N2 Sleep Stage as Measured by Polysomnography at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Percentage of Total Sleep Time Spent in the N2 Sleep Stage at Week 4/10
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Mean Change From Baseline in the Total Time Spent in Stage N3 Sleep Time at Week 4/10 Measured by PSG Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Percentage of Total Sleep Time Spent in the N3 Sleep Stage at Week 4/10
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in Time Spent in the REM (Rapid Eye Movement) Sleep Stage at Week 4/10 as Measured by Polysomnography Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Percentage of Total Sleep Time Spent in the REM Sleep Stage at Week 4/10
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in Periodic Limb Movements Causing Awakening (PLMAWI) at Week 4/10 as Measured by Polysomnography Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Number of PLMAI Responders at Week 4/10 Using LOCF
timeFrame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in Sleep Quality at Week 4/10 as Measured by the Subjective Post Sleep Diary (SPSD) Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in Participant's Ratings of Feeling Rested Upon Awakening as Measured by the Subjective Post Sleep Diary (SPSD) at Week 4/10 Using LOCF.
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Number of Awakenings Measured Objectively by Polysomnography at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Self-reported Number of Hours Spent Awake During the Night (SPSD) Due to RLS at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Number of Participants With no Self-reported Awakenings (SPSD) Due to RLS at Week 4/10 Using LOCF
timeFrame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Total Sleep Time Measured by Polysomnography (PSG) at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Sleep Efficiency Measured by Polysomnography (PSG) at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Wake After Sleep Onset (WASO) Measured by Polysomnography (PSG) at Week 4/10 Using LOCF.
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Suggested Immobilization Test (SIT) PLM Index at Week 4/10
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the SIT MDS (Mean Leg Discomfort Score), Mean of Scores From 0 to 60 Minutes, at Week 4/10
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Number of Participants Who Responded Affirmatively to Each of the 4 Items of the Participant-completed Patient Global Impression of Therapy at Week 4/10 Using LOCF
timeFrame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Adjusted Mean Change From Baseline in the Clinical Global Impression of Illness - Severity (CGI-S) Score at Week 4/10 Using LOCF
timeFrame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Number of Participants Who Were Defined as Clinical Global Impression of Illness (CGI-I) Scale "Responders" at Week 4/10 Using LOCF
timeFrame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
measure: Number of Participants Who Self-reported "Very Satisfied" or "Satisfied" With the Investigational Product at Week 4/10 Using LOCF
timeFrame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)
Other outcomes:
Locations:
city: Jasper
country: United States
facility: GSK Investigational Site
state: Alabama
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Hallandale Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Macon
country: United States
facility: GSK Investigational Site
state: Georgia
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
city: Crestview Hills
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Chevy Chase
country: United States
facility: GSK Investigational Site
state: Maryland
city: Brighton
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Kalamazoo
country: United States
facility: GSK Investigational Site
state: Michigan
city: West Seneca
country: United States
facility: GSK Investigational Site
state: New York
city: Greenville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dublin
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Walla Walla
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Calloway M, Bharmal M, Hill-Zabala C, Allen R. Development and validation of a subjective post sleep diary (SPSD) to assess sleep status in subjects with restless legs syndrome. Sleep Med. 2011 Aug;12(7):704-10. doi: 10.1016/j.sleep.2010.09.020. Epub 2011 Jul 5.