Long-Term Study of Gabapentin Enacarbil (GEn, XP13512) vs. Placebo in Patients With Restless Legs Syndrome.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
XenoPort, Inc.
ClinicalTrials.gov Identifier:
NCT00311363
First received: April 3, 2006
Last updated: July 15, 2013
Last verified: May 2011
Results First Received: April 28, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Restless Legs Syndrome
Interventions: Drug: GEn (XP13512)
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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
There were 27 participants who completed the Single-blind Treatment Period who either elected not to enroll into the Double-blind Treatment Period or were considered non-responders and were not randomized.

Reporting Groups
  Description
Single-blind (SB) GEn 1200 mg Oral gabapentin enacarbil (GEn; XP13512/GSK1838262) 1200 milligrams (mg) once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 168: two ER tablets (total dose of 1200 mg GEn).
DB Placebo Days 169 to 182: one 600 mg ER tablet of GEn and one matching placebo tablet for a 2-week blinded taper period. Days 183 to 252: two blinded placebo tablets. Days 253 to 260, participants tapered to one placebo tablet.
DB GEn 1200 mg Days 169 to 252: two 600 mg ER tablets (1200 mg GEn). Days 253 to 260, participants tapered to one 600 mg ER tablet.

Participant Flow for 2 periods

Period 1:   24-Week Single-Blind Treatment Period
    Single-blind (SB) GEn 1200 mg     DB Placebo     DB GEn 1200 mg  
STARTED     327     0     0  
COMPLETED     221     0     0  
NOT COMPLETED     106     0     0  
Adverse Event                 42                 0                 0  
Lack of Efficacy                 13                 0                 0  
Withdrawal by Subject                 27                 0                 0  
Lost to Follow-up                 12                 0                 0  
Protocol Violation                 8                 0                 0  
Elective Surgery                 1                 0                 0  
Work Shift Changed to Evenings                 1                 0                 0  
Pregnancy                 1                 0                 0  
Death                 1                 0                 0  

Period 2:   12-Week Double-Blind Treatment Period
    Single-blind (SB) GEn 1200 mg     DB Placebo     DB GEn 1200 mg  
STARTED     0     98     96  
COMPLETED     0     84     84  
NOT COMPLETED     0     14     12  
Adverse Event                 0                 3                 0  
Lost to Follow-up                 0                 1                 2  
Lack of Efficacy                 0                 6                 4  
Withdrawal by Subject                 0                 2                 4  
Protocol Violation                 0                 1                 2  
Per Sponsor, Unknown                 0                 1                 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.

Single-blind (SB) Safety Population: subjects who received at least 1 dose of SB study drug

1 subject withdrew from the SB period prior to receiving drug due to protocol non-compliance, and thus was excluded from the SB-Safety Population


Reporting Groups
  Description
SB GEn 1200 mg Oral gabapentin enacarbil (GEn; XP13512/GSK1838262) 1200 milligrams (mg) once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 168: two ER tablets (total dose of 1200 mg GEn).
DB Placebo Days 169 to 182: one 600 mg ER tablet of GEn and one matching placebo tablet for a 2-week blinded taper period. Days 183 to 252: two blinded placebo tablets. Days 253 to 260, participants tapered to one placebo tablet.
DB GEn 1200 mg Days 169 to 252: two 600 mg ER tablets (1200 mg GEn). Days 253 to 260, participants tapered to one 600 mg ER tablet.
Total Total of all reporting groups

Baseline Measures
    SB GEn 1200 mg     DB Placebo     DB GEn 1200 mg     Total  
Number of Participants  
[units: participants]
  326     98     96     520  
Age [1]
[units: Years]
Mean ± Standard Deviation
  49.8  ± 12.38     52.2  ± 12.07     50.7  ± 11.68     51.5  ± 11.87  
Gender [1]
[units: Participants]
       
Female     188     53     62     303  
Male     138     45     34     217  
Race/Ethnicity, Customized [2]
[units: participants]
       
White or Caucasian     305     92     93     490  
Black or African American     16     5     2     23  
American Indian or Alaska Native     1     0     0     1  
Hispanic     3     1     1     5  
Other, Syrian     1     0     0     1  
[1] The Safety Population (all participants who received at least one dose [or any portion of a dose] of study drug) was used for all baseline characteristics.
[2] The Safety Population (all participants received at least one dose [or any portion of a dose] of study drug) was used for all baseline characteristics.



  Outcome Measures
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1.  Primary:   Percentage of Participants Who Experienced a Relapse During the Double-Blind Treatment Period   [ Time Frame: DB Treatment Period; Days 169 to 252 (Weeks 24 to 36) ]

2.  Secondary:   Time From Randomization to Relapse in RLS Symptoms During the Double-Blind Treatment Period   [ Time Frame: DB Treatment Period; Days 169 to 252 (Weeks 24 to 36) ]

3.  Secondary:   Time From Randomization to Relapse in RLS Symptoms During the Double-Blind Treatment Period (Excluding First Two Weeks of DB Phase)   [ Time Frame: DB Treatment Period; Days 184 to 252 (Weeks 26 to 36) ]

4.  Secondary:   Mean Change From Randomization to Week 36 (or End of Treatment) in the IRLS Rating Scale (IRLS) Total Score Using Last Observation Carried Forward (LOCF)   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

5.  Secondary:   Percentage of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated Clinical Global Impression of Change (CGI-C) Scale as a Dichotomous Variable at Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

6.  Secondary:   Number of Participants in Each Category of the Investigator-Rated CGI-C at Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

7.  Secondary:   Number of Participants in Each Category of the Participant-Rated CGI-I Scale at Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Week 36 (or end of DB treatment) ]

8.  Secondary:   Percentage of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Week 36 (or end of DB treatment) ]

9.  Secondary:   Mean Change From Randomization to Week 36 (DB Treatment Phase) in the Mean Daytime Somnolence Domain Score of the Medical Outcomes Study (MOS) Sleep Scale Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

10.  Secondary:   Mean Change From Randomization to Week 36 (DB Treatment Phase) in the Mean Sleep Disturbance Domain Score of the MOS Sleep Scale Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

11.  Secondary:   Change From Randomization to Week 36 (DB Treatment Phase) in the Mean Sleep Adequacy Domain Score of the MOS Sleep Scale Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

12.  Secondary:   Change From Randomization to Week 36 (DB Treatment Phase) in the Mean Sleep Quantity Domain Score of the MOS Sleep Scale Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

13.  Secondary:   Change From Randomization to Week 36 (DB Treatment Phase) in the RLS Quality of Life (QoL) Overall Life-Impact Score   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

14.  Secondary:   Number of Participants With no Reported RLS Symptoms (Sx) During Each of the 4-hour Periods From the 24-hour RLS Record at Week 36 (DB Treatment Phase)   [ Time Frame: Week 36 (or end of DB treatment) ]

15.  Secondary:   Median Time to Onset of First RLS Symptoms Using the 24-hour RLS Symptom Record at Week 36 (DB Treatment Phase)   [ Time Frame: Week 36 (or end of DB treatment) ]

16.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire (PSQ) Responses to the Question Regarding Their Overall Quality of Sleep in the Week Prior to Measurement at Randomization and Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

17.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire (PSQ) Responses to the Question Regarding Their Ability to Function in the Week Prior to Measurement at Randomization and Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

18.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire Responses to the Question Regarding the Number of Nights With RLS Symptoms in the Week Prior to Measurement at Randomization and Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

19.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire Responses to the Question Regarding the Number of Awakenings During Night Due to RLS Symptoms in the Week Prior to Measurement at Randomization and Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

20.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire Responses to the Question Regarding the Number of Hours Awake Per Night Due to RLS Symptoms in the Week Prior to Measurement at Randomization and Week 36 (DB Treatment Phase) Using LOCF   [ Time Frame: Randomization (Week 24) and Week 36 (or end of DB treatment) ]

21.  Secondary:   Mean Change From Baseline in the IRLS Scale Total Score at Week 24 (SB Treatment Phase) Using LOCF   [ Time Frame: Days 1 to 168 (Baseline to Week 24 of SB Phase) ]

22.  Secondary:   Number of Participants in Each Category of the Investigator-Rated CGI-I at Week 24/End of Treatment (SB Treatment Phase) Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

23.  Secondary:   Number of Participants in Each Category of the Participant-Rated CGI-I at Week 24/End of Treatment (SB Treatment Phase) Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

24.  Secondary:   Mean Change From Baseline to Week 24 (SB Treatment Period) in the Mean Daytime Somnolence Domain Score of the Medical Outcomes Study (MOS) Sleep Scale Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

25.  Secondary:   Mean Change From Baseline to Week 24 (SB Treatment Period) in the Mean Sleep Disturbance Domain Score of the MOS Sleep Scale Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

26.  Secondary:   Mean Change From Baseline to Week 24 (SB Treatment Period) in the Mean Sleep Adequacy Domain Score of the MOS Sleep Scale Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

27.  Secondary:   Mean Change From Baseline in the MOS Sleep Scale Domain, Sleep Quantity, Score at Week 24 (SB Treatment Period) Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

28.  Secondary:   Mean Change From Baseline in the Overall Quality of Life Impact Score of the RLS Quality of Life (QoL) Questionnaire at Week 24 (SB Treatment Phase)   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

29.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire Responses to the Question Regarding the Overall Quality of Sleep in the Week Prior to Measurement at Baseline and Week 24 (SB Treatment Period) Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

30.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire Responses to the Question Regarding the Ability to Function in the Week Prior to Measurement at Baseline and Week 24 (SB Treatment Period) Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

31.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire Responses to the Question Regarding the Number of Nights With RLS Symptoms in the Week Prior to Measurement at Baseline and Week 24 (SB Treatment Period) Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

32.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire Responses to the Question Regarding the Number of Awakenings During the Night Due to RLS Symptoms in the Week Prior to Measurement at Baseline and Week 24 (SB Treatment Period) Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]

33.  Secondary:   Number of Participants With the Indicated Post-Sleep Questionnaire Responses to the Question Regarding the Number of Hours Awake Per Night Due to RLS Symptoms in the Week Prior to Measurement at Baseline and Week 24 (SB Treatment Period) Using LOCF   [ Time Frame: Baseline and Day 168 or Week 24/End of Treatment of SB Treatment Phase ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: XenoPort Call Center
Organization: XenoPort, Inc.
phone: 877-936-6778


Publications:

Responsible Party: XenoPort, Inc.
ClinicalTrials.gov Identifier: NCT00311363     History of Changes
Other Study ID Numbers: 111461, XP060
Study First Received: April 3, 2006
Results First Received: April 28, 2011
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration