Trial Outcomes & Findings for Gabapentin Enacarbil (GSK1838262) Adult Restless Leg Syndrome (RLS) Post Marketing Commitment Study (NCT NCT01668667)

Last Updated: 2021-05-24

Results Overview

International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0. Change from Baseline = LOCF value at current visit - value at Baseline (the last nonmissing assessment before the first dose of study medication). A negative treatment difference indicates a benefit relative to placebo. The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

501 participants

Primary outcome timeframe

Baseline, 12 weeks

Results posted on

2021-05-24

Participant Flow

Participant milestones

Participant milestones
Measure	GSK1838262 600 mg Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match Once-daily dose with food in the evening at approximately 5 PM
Overall Study STARTED	126	125	125	125
Overall Study COMPLETED	95	99	94	102
Overall Study NOT COMPLETED	31	26	31	23

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK1838262 600 mg Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match Once-daily dose with food in the evening at approximately 5 PM
Overall Study Adverse Event	3	6	4	4
Overall Study Lack of Efficacy	3	2	2	3
Overall Study Protocol Violation	6	10	12	5
Overall Study Lost to Follow-up	9	4	7	6
Overall Study Physician Decision	3	0	1	0
Overall Study Withdrawal by Subject	7	4	5	5

Baseline Characteristics

Gabapentin Enacarbil (GSK1838262) Adult Restless Leg Syndrome (RLS) Post Marketing Commitment Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK1838262 600 mg n=119 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg n=112 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg n=111 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match n=117 Participants Once-daily dose with food in the evening at approximately 5 PM	Total n=459 Participants Total of all reporting groups
Age, Continuous	49.2 years STANDARD_DEVIATION 12.92 • n=93 Participants	52.1 years STANDARD_DEVIATION 12.22 • n=4 Participants	52.0 years STANDARD_DEVIATION 14.51 • n=27 Participants	52.1 years STANDARD_DEVIATION 13.01 • n=483 Participants	51.3 years STANDARD_DEVIATION 13.20 • n=36 Participants
Sex: Female, Male Female	73 Participants n=93 Participants	69 Participants n=4 Participants	71 Participants n=27 Participants	64 Participants n=483 Participants	277 Participants n=36 Participants
Sex: Female, Male Male	46 Participants n=93 Participants	43 Participants n=4 Participants	40 Participants n=27 Participants	53 Participants n=483 Participants	182 Participants n=36 Participants
Race/Ethnicity, Customized African American/African Heritage	6 participants n=93 Participants	14 participants n=4 Participants	12 participants n=27 Participants	8 participants n=483 Participants	40 participants n=36 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants
Race/Ethnicity, Customized Asian	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	0 participants n=36 Participants
Race/Ethnicity, Customized White	112 participants n=93 Participants	97 participants n=4 Participants	95 participants n=27 Participants	109 participants n=483 Participants	413 participants n=36 Participants
Race/Ethnicity, Customized White & African American/African Heritage	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants
Race/Ethnicity, Customized White & Asian	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants
Race/Ethnicity, Customized Unknown or not Reported	0 participants n=93 Participants	0 participants n=4 Participants	2 participants n=27 Participants	0 participants n=483 Participants	2 participants n=36 Participants
IRLS Rating Scale Total Score, Continuous	23.4 units on a scale STANDARD_DEVIATION 5.61 • n=93 Participants	24.0 units on a scale STANDARD_DEVIATION 5.23 • n=4 Participants	23.7 units on a scale STANDARD_DEVIATION 5.25 • n=27 Participants	23.5 units on a scale STANDARD_DEVIATION 5.34 • n=483 Participants	23.6 units on a scale STANDARD_DEVIATION 5.35 • n=36 Participants

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Population: mITT (modified intent to treat) Population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.

Outcome measures

Outcome measures
Measure	GSK1838262 600 mg n=119 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg n=112 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg n=111 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match n=117 Participants Once-daily dose with food in the evening at approximately 5 PM
The Change From Baseline to the End of Treatment in the International Restless Legs Syndrome (IRLS) Rating Scale Score	-12.50 units on a scale Standard Error 0.745	-12.54 units on a scale Standard Error 0.764	-11.48 units on a scale Standard Error 0.767	-9.93 units on a scale Standard Error 0.753

PRIMARY outcome

Timeframe: 12 weeks

Population: mITT (modified intent to treat) population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.

Clinical Global Impression - Improvement Scale (CGI-I): 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), on the scale. Higher score = more affected. Number of subjects responding to treatment at Week 12 with respect to dose level. CGI-I Responders = subjects who reported CGI-I scores of very much improved or much improved.

Outcome measures

Outcome measures
Measure	GSK1838262 600 mg n=119 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg n=112 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg n=111 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match n=117 Participants Once-daily dose with food in the evening at approximately 5 PM
The Proportion of Subjects at the End of Treatment Who Are Responders With Either "Much Improved" or "Very Much Improved" on the Investigator-rated Clinical Global Impression of Improvement (CGI-I)	67 percentage of participants	67 percentage of participants	68 percentage of participants	50 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0. This model only includes treatment in the model. Least squares mean is used for analysis.

Outcome measures

Outcome measures
Measure	GSK1838262 600 mg n=119 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg n=112 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg n=111 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match n=117 Participants Once-daily dose with food in the evening at approximately 5 PM
The Dose-response Relationship of Change From Baseline in IRLS Rating Scale Total Score at End of Treatment	-12.1 units on a scale Standard Error 0.80	-12.7 units on a scale Standard Error 0.82	-11.3 units on a scale Standard Error 0.83	-9.8 units on a scale Standard Error 0.80

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	GSK1838262 600 mg n=119 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg n=112 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg n=111 Participants Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match n=117 Participants Once-daily dose with food in the evening at approximately 5 PM
The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment Responder	67 percentage of participants	67 percentage of participants	68 percentage of participants	50 percentage of participants
The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment Non-Responder	33 percentage of participants	33 percentage of participants	32 percentage of participants	50 percentage of participants

Adverse Events

GSK1838262 600 mg

Serious events: 1 serious events

Other events: 55 other events

Deaths: 0 deaths

GSK1838262 450 mg

Serious events: 0 serious events

Other events: 56 other events

Deaths: 0 deaths

GSK1838262 300 mg

Serious events: 2 serious events

Other events: 33 other events

Deaths: 0 deaths

GSK1838262 Placebo Match

Serious events: 1 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GSK1838262 600 mg n=122 participants at risk Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg n=123 participants at risk Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg n=121 participants at risk Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match n=121 participants at risk Once-daily dose with food in the evening at approximately 5 PMmatching placebo.
Injury, poisoning and procedural complications Ligament rupture	0.82% 1/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.
Cardiac disorders Coronary artery disease	0.00% 0/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.83% 1/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.83% 1/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.83% 1/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.

Other adverse events

Other adverse events
Measure	GSK1838262 600 mg n=122 participants at risk Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 450 mg n=123 participants at risk Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 300 mg n=121 participants at risk Once-daily dose with food in the evening at approximately 5 PM	GSK1838262 Placebo Match n=121 participants at risk Once-daily dose with food in the evening at approximately 5 PMmatching placebo.
Nervous system disorders Somnolence	10.7% 13/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	16.3% 20/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	9.9% 12/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	6.6% 8/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.
Nervous system disorders Headache	9.0% 11/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	7.3% 9/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	8.3% 10/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	9.9% 12/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.
Nervous system disorders Dizziness	12.3% 15/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	6.5% 8/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	4.1% 5/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	4.1% 5/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	4.9% 6/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	8.1% 10/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	2.5% 3/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	5.8% 7/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.
Gastrointestinal disorders Nausea	4.1% 5/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	3.3% 4/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	2.5% 3/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	5.8% 7/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.
General disorders Fatigue	4.1% 5/122 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	4.1% 5/123 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	0.00% 0/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.	5.8% 7/121 • AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to & including any follow-up contact All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.

Additional Information

XenoPort Call Center

XenoPort, Inc.

Phone: 877-936-6778

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER