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Polysomnography Study of GSK1838262 Extended Release Tablets Versus Placebo in RLS and Associated Sleep Disturbance

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
XenoPort, Inc.
ClinicalTrials.gov Identifier:
NCT00748098
First received: September 5, 2008
Last updated: July 15, 2013
Last verified: January 2013
Results First Received: April 21, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Restless Legs Syndrome
Restless Legs Syndrome (RLS)
Interventions: Drug: GSK1838262 Extended Release Tablets
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Placebo Followed by GEn 1200 mg/Day Participants randomized to matching placebo administered once daily with food at 5 pm during the 28-day First Treatment Intervention Period and the 7-day First Taper Period. No treatment was given during the 7-day Washout. Gabapentin enacarbil (GEn) 1200 mg/day administered once daily with food at 5 pm during the 28-day Second Treatment Intervention Period (Days 1-3, 600 mg). GEn 600 mg administered once daily with food at 5 pm during the 7-day Second Taper Period. No treatment was given during Follow-up.
GEn 1200 mg/Day Followed by Placebo Participants randomized to GEn 1200 mg/day administered once daily with food at 5 pm during the 28-day First Treatment Intervention Period (Days 1-3, 600 mg). GEn 600 mg administered once daily with food at 5 pm during the 7-day First Taper Period. No treatment was given during 7-day Washout. Matching placebo administered once daily with food at 5 pm during the 28-day Second Treatment Intervention Period and the 7-day Second Taper Period. No treatment was given during Follow-up.

Participant Flow for 5 periods

Period 1:   First Treatment Intervention Period
    Placebo Followed by GEn 1200 mg/Day     GEn 1200 mg/Day Followed by Placebo  
STARTED     69     67  
COMPLETED     64     66  
NOT COMPLETED     5     1  
Adverse Event                 1                 1  
Protocol Violation                 1                 0  
Lost to Follow-up                 1                 0  
Withdrawal by Subject                 2                 0  

Period 2:   First Taper Period
    Placebo Followed by GEn 1200 mg/Day     GEn 1200 mg/Day Followed by Placebo  
STARTED     64     66  
COMPLETED     61     65  
NOT COMPLETED     3     1  
Protocol Violation                 1                 0  
Withdrawal by Subject                 2                 0  
Protocol Stopping Criteria Met                 0                 1  

Period 3:   1-Week Washout Period
    Placebo Followed by GEn 1200 mg/Day     GEn 1200 mg/Day Followed by Placebo  
STARTED     61     65  
COMPLETED     59     64  
NOT COMPLETED     2     1  
Adverse Event                 0                 1  
Withdrawal by Subject                 2                 0  

Period 4:   Second Treatment Intervention Period
    Placebo Followed by GEn 1200 mg/Day     GEn 1200 mg/Day Followed by Placebo  
STARTED     59     64  
COMPLETED     53     61  
NOT COMPLETED     6     3  
Adverse Event                 4                 1  
Lost to Follow-up                 1                 1  
Withdrawal by Subject                 1                 1  

Period 5:   Second Taper Period
    Placebo Followed by GEn 1200 mg/Day     GEn 1200 mg/Day Followed by Placebo  
STARTED     53     61  
COMPLETED     53     61  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
All Participants in the Intent-to-Treat (ITT) Population All randomized participants who took at least one dose of study drug and had at least one post-baseline polysomnography (PSG) efficacy assessment

Baseline Measures
    All Participants in the Intent-to-Treat (ITT) Population  
Number of Participants  
[units: participants]
  131  
Age [1]
[units: Years]
Mean ± Standard Deviation
  52.0  ± 12.70  
Gender [1]
[units: Participants]
 
Female     76  
Male     55  
Race/Ethnicity, Customized [1]
[units: participants]
 
African American/African Heritage     7  
American Indian or Alaska Native     2  
Asian     1  
White     120  
Mixed Race     1  
[1] Baseline characteristics were collected for all participants prior to the Baseline period and are summarized independent of treatment sequence. The ITT Population consisted of all randomized participants who took at least one dose of investigational product, and had at least one post-baseline polysomnography (PSG) sleep efficacy assessment.



  Outcome Measures
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1.  Primary:   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)   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

2.  Secondary:   Adjusted Mean Change From Baseline in Periodic Limb Movements Associated With Arousal (PLMAI) at Week 4/10 as Measured by Polysomnography Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

3.  Secondary:   Adjusted Mean Change From Baseline in the International Restless Legs Rating Scale (IRLS) Total Score at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

4.  Secondary:   Adjusted Mean Change From Baseline in the Item 4 (Sleep Disturbance) Scores of the IRLS Rating Scale at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

5.  Secondary:   Adjusted Mean Change From Baseline in Time Spent in N1 Sleep as Measured by Polysomnography at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

6.  Secondary:   Adjusted Mean Change From Baseline in the Percentage of Total Sleep Time Spent in the N1 Sleep Stage at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

7.  Secondary:   Adjusted Mean Change From Baseline in Time Spent in the N2 Sleep Stage as Measured by Polysomnography at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

8.  Secondary:   Adjusted Mean Change From Baseline in the Percentage of Total Sleep Time Spent in the N2 Sleep Stage at Week 4/10   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

9.  Secondary:   Mean Change From Baseline in the Total Time Spent in Stage N3 Sleep Time at Week 4/10 Measured by PSG Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

10.  Secondary:   Adjusted Mean Change From Baseline in the Percentage of Total Sleep Time Spent in the N3 Sleep Stage at Week 4/10   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

11.  Secondary:   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   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]
  Hide Outcome Measure 11

Measure Type Secondary
Measure Title 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
Measure Description In REM sleep, a participant’s breathing becomes more rapid, irregular, and shallow; eyes jerk rapidly; and limb muscles are temporarily paralyzed. Brain waves during this stage increase to levels experienced when a person is awake. This is the stage when most dreams occur. Change from baseline was calculated as the Week 4 and Week 10 values minus the baseline value. Mean change from baseline was adjusted for treatment, pooled center, and period effects.
Time Frame Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Population: Of the 131 ITT participants, 2 and 6 participants did not take Placebo and GEn 1200 mg, respectively, in the second period. In addition, 6 placebo and 4 GEn 1200 participants did not have PSG data during the second intervention period and were therefore not included in this analysis.

Reporting Groups
  Description
Placebo Placebo once daily either in first intervention period or second intervention period
GEn 1200 mg GEn 1200 mg once daily either in first intervention period or second intervention period

Measured Values
    Placebo     GEn 1200 mg  
Number of Participants Analyzed  
[units: participants]
  123     121  
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  
[units: minutes]
Least Squares Mean ± Standard Error
  -1.21  ± 2.638     4.22  ± 2.659  

No statistical analysis provided for 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



12.  Secondary:   Adjusted Mean Change From Baseline in the Percentage of Total Sleep Time Spent in the REM Sleep Stage at Week 4/10   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

13.  Secondary:   Adjusted Mean Change From Baseline in Periodic Limb Movements Causing Awakening (PLMAWI) at Week 4/10 as Measured by Polysomnography Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

14.  Secondary:   Number of PLMAI Responders at Week 4/10 Using LOCF   [ Time Frame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

15.  Secondary:   Adjusted Mean Change From Baseline in Sleep Quality at Week 4/10 as Measured by the Subjective Post Sleep Diary (SPSD) Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

16.  Secondary:   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.   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

17.  Secondary:   Adjusted Mean Change From Baseline in the Number of Awakenings Measured Objectively by Polysomnography at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

18.  Secondary:   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   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

19.  Secondary:   Number of Participants With no Self-reported Awakenings (SPSD) Due to RLS at Week 4/10 Using LOCF   [ Time Frame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

20.  Secondary:   Adjusted Mean Change From Baseline in the Total Sleep Time Measured by Polysomnography (PSG) at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

21.  Secondary:   Adjusted Mean Change From Baseline in the Sleep Efficiency Measured by Polysomnography (PSG) at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

22.  Secondary:   Adjusted Mean Change From Baseline in the Wake After Sleep Onset (WASO) Measured by Polysomnography (PSG) at Week 4/10 Using LOCF.   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

23.  Secondary:   Adjusted Mean Change From Baseline in the Suggested Immobilization Test (SIT) PLM Index at Week 4/10   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

24.  Secondary:   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   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

25.  Secondary:   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   [ Time Frame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

26.  Secondary:   Adjusted Mean Change From Baseline in the Clinical Global Impression of Illness – Severity (CGI-S) Score at Week 4/10 Using LOCF   [ Time Frame: Baseline, Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

27.  Secondary:   Number of Participants Who Were Defined as Clinical Global Impression of Illness (CGI-I) Scale "Responders" at Week 4/10 Using LOCF   [ Time Frame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]

28.  Secondary:   Number of Participants Who Self-reported “Very Satisfied” or “Satisfied” With the Investigational Product at Week 4/10 Using LOCF   [ Time Frame: Week 4/10 (representing the last week of each intervention period, i.e. Weeks 4 and 10) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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