Polysomnography Study of GSK1838262 (XP13512) Extended Release Tablets Versus Placebo in Restless Legs Syndrome (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: January 28, 2013

Last verified: January 2013

History of Changes

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.

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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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) ]

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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) ]

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Measure Type	Secondary
Measure Title	Adjusted Mean Change From Baseline in Periodic Limb Movements Associated With Arousal (PLMAI) at Week 4/10 as Measured by Polysomnography Using LOCF
Measure Description	PLMAI is defined as the number of Periodic Limb Movements (PLMs or involuntary jerks of the legs that cause a participant to arouse from sleep per hour of sleep). 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 Periodic Limb Movements Associated With Arousal (PLMAI) at Week 4/10 as Measured by Polysomnography Using LOCF [units: limb movements per hour] Least Squares Mean ± Standard Error	-1.52 ± 0.892	-4.59 ± 0.899

Statistical Analysis 1 for Adjusted Mean Change From Baseline in Periodic Limb Movements Associated With Arousal (PLMAI) at Week 4/10 as Measured by Polysomnography Using LOCF

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.002
Adjusted mean difference versus placebo ^[4]	-3.07
95% Confidence Interval	( -5.04 to -1.10 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
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[2]	Other relevant information, such as adjustments or degrees of freedom:
	Estimates were obtained using an ANCOVA model with period, group center, and treatment as fixed effects and participant as a random effect.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[4]	Other relevant estimation information:
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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) ]

Show Outcome Measure 3

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) ]

Show Outcome Measure 4

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) ]

Show Outcome Measure 5

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) ]

Show Outcome Measure 6

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) ]

Show Outcome Measure 7

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) ]

Show Outcome Measure 8

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) ]

Show Outcome Measure 9

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) ]

Show Outcome Measure 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) ]

Show Outcome Measure 11

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) ]

Show Outcome Measure 12

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) ]

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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) ]

Show Outcome Measure 14

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) ]

Show Outcome Measure 15

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) ]

Show Outcome Measure 16

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) ]

Show Outcome Measure 17

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) ]

Show Outcome Measure 18

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) ]

Show Outcome Measure 19

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) ]

Show Outcome Measure 20

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) ]

Show Outcome Measure 21

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) ]

Show Outcome Measure 22

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) ]

Show Outcome Measure 23

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) ]

Show Outcome Measure 24

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) ]

Show Outcome Measure 25

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) ]

Show Outcome Measure 26

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) ]

Show Outcome Measure 27

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) ]

Show Outcome Measure 28

Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

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: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided

Responsible Party:	XenoPort, Inc.
ClinicalTrials.gov Identifier:	NCT00748098 History of Changes
Other Study ID Numbers:	RXP110908
Study First Received:	September 5, 2008
Results First Received:	April 21, 2011
Last Updated:	January 28, 2013
Health Authority:	United States: Food and Drug Administration

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