Trial Outcomes & Findings for Simulated Driving Study in Restless Legs Syndrome (NCT NCT01332318)

NCT ID: NCT01332318

Last Updated: 2013-07-26

Results Overview

Lane position variability (LPV) was defined as the standard deviation of lane position, and was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall LPV was calculated as the Day 16 mean LPV over the 1-hour drive minus the Baseline mean LPV over the 1-hour drive. The Day 16 measurement is at the time of maximum concentration (Tmax) for both GEn and DPH.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 130 participants
• Primary outcome timeframe: Baseline (Day -1) and Day 16
• Results posted on: 2013-07-26

Participant Flow

Participant milestones

Measure	GEn Placebo and DPH Placebo Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Overall Study STARTED	34	32	34	30
Overall Study COMPLETED	32	28	33	28
Overall Study NOT COMPLETED	2	4	1	2

Reasons for withdrawal

Measure	GEn Placebo and DPH Placebo Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Overall Study Adverse Event	0	3	0	0
Overall Study Withdrawal by Subject	1	1	0	1
Overall Study Protocol Violation	1	0	1	1

Baseline Characteristics

Simulated Driving Study in Restless Legs Syndrome

Baseline characteristics by cohort

Measure	GEn Placebo and DPH Placebo n=34 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=31 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=34 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=30 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	Total n=129 Participants Total of all reporting groups
Age Continuous	49.6 Years STANDARD_DEVIATION 11.40 • n=5 Participants	46.8 Years STANDARD_DEVIATION 11.31 • n=7 Participants	49.3 Years STANDARD_DEVIATION 10.27 • n=5 Participants	40.6 Years STANDARD_DEVIATION 11.80 • n=4 Participants	46.8 Years STANDARD_DEVIATION 11.62 • n=21 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	21 Participants n=7 Participants	17 Participants n=5 Participants	19 Participants n=4 Participants	77 Participants n=21 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants	11 Participants n=4 Participants	52 Participants n=21 Participants
Race/Ethnicity, Customized White or Caucasian	34 participants n=5 Participants	31 participants n=7 Participants	33 participants n=5 Participants	30 participants n=4 Participants	128 participants n=21 Participants
Race/Ethnicity, Customized Other, Unknown	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 16

Population: Modified Intent-to-Treat (MITT) Population: all participants in the Safety Population who completed at least one Baseline and one End of Study (Days 14-16) simulated driving assessment. The number of participants assessed at each study day varies due to incomplete/missing data.

Lane position variability (LPV) was defined as the standard deviation of lane position, and was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall LPV was calculated as the Day 16 mean LPV over the 1-hour drive minus the Baseline mean LPV over the 1-hour drive. The Day 16 measurement is at the time of maximum concentration (Tmax) for both GEn and DPH.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=30 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)	-0.10 feet Standard Error 0.06	0.15 feet Standard Error 0.06	0.15 feet Standard Error 0.06	0.16 feet Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline (Days -1 and 1) and Days 14 and 15

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Lane position variability (LPV) was defined as the standard deviation of lane position, and was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall LPV was calculated as the Day 14 (in the evening) or Day 15 (in the morning after GEn dosed at 5 PM) mean LPV over the 1-hour drive minus the Baseline (Day -1 or Day 1) mean LPV over the 1-hour drive.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV) Day 14, n=33, 28, 33, 28	-0.06 feet Standard Deviation 0.17	0.17 feet Standard Deviation 0.43	-0.01 feet Standard Deviation 0.28	-0.08 feet Standard Deviation 0.15
Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV) Day 15, n=32, 28, 31, 27	-0.01 feet Standard Deviation 0.14	0.13 feet Standard Deviation 0.40	0.02 feet Standard Deviation 0.32	-0.10 feet Standard Deviation 0.19

SECONDARY outcome

Timeframe: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Lane position was measured from the center line of the 26 foot wide 2-lane paved road to the center of the vehicle. Change from baseline in overall average lane position was calculated as the Day 14 (in the evening), 15 (in the morning after GEn dosed at 5 PM), or 16 (assessment at Tmax of GEn and DPH) mean lane position over the 1-hour drive minus the Baseline (Days -1 and 1) mean lane position over the 1-hour drive.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position Day 14, n=33, 28, 33, 28	0.05 feet Standard Deviation 0.35	-0.02 feet Standard Deviation 0.64	0.03 feet Standard Deviation 0.32	0.08 feet Standard Deviation 0.29
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position Day 15, n=32, 28, 31, 27	0.01 feet Standard Deviation 0.35	0.12 feet Standard Deviation 0.39	0.04 feet Standard Deviation 0.34	0.04 feet Standard Deviation 0.28
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position Day 16, n=30, 28, 33, 28	0.17 feet Standard Deviation 0.44	0.13 feet Standard Deviation 0.48	0.14 feet Standard Deviation 0.32	0.08 feet Standard Deviation 0.31

SECONDARY outcome

Timeframe: Baseline (Day -1) and Days 14 and 16; baseline (Day 1) and Day 15

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Speed variability was defined as the standard deviation of the speed (measured in miles per hour). Participants were instructed to maintain a speed of 55 miles per hour during the test drive. Change from baseline in overall speed variability was calculated as the Day 14 (in the evening), 15 (in the morning), or 16 (at Tmax of GEn and DPH) mean speed variability over the 1-hour drive minus the Baseline (Days -1 and 1) mean speed variability over the 1-hour drive.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability Day 14, n=33, 28, 33, 28	-0.22 miles per hour Standard Deviation 0.63	-0.19 miles per hour Standard Deviation 1.42	-0.32 miles per hour Standard Deviation 1.17	-0.47 miles per hour Standard Deviation 0.96
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability Day 15, n=32, 28, 31, 27	-0.26 miles per hour Standard Deviation 0.48	0.43 miles per hour Standard Deviation 2.22	-0.07 miles per hour Standard Deviation 0.69	-0.33 miles per hour Standard Deviation 0.43
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability Day 16, n=30, 28, 33, 28	-0.54 miles per hour Standard Deviation 0.55	-0.12 miles per hour Standard Deviation 2.02	0.23 miles per hour Standard Deviation 1.95	-0.08 miles per hour Standard Deviation 1.11

SECONDARY outcome

Timeframe: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Participants were instructed to maintain a speed of 55 miles per hour during the driving assessment. Change from baseline in overall average speed was calculated as the Day 14 (in the evening), 15 (in the morning), or 16 (at Tmax of GEn and DPH) mean speed over the 1-hour drive minus the Baseline (Days -1 and 1) mean speed over the 1-hour drive.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed Day 14, n=33, 28, 33, 28	1.24 miles per hour Standard Deviation 1.49	0.66 miles per hour Standard Deviation 1.34	0.42 miles per hour Standard Deviation 1.43	0.12 miles per hour Standard Deviation 1.51
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed Day 15, n=32, 28, 31, 27	0.75 miles per hour Standard Deviation 1.75	0.33 miles per hour Standard Deviation 0.97	0.30 miles per hour Standard Deviation 1.12	0.37 miles per hour Standard Deviation 1.04
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed Day 16, n=30, 28, 33, 28	1.70 miles per hour Standard Deviation 1.92	0.90 miles per hour Standard Deviation 1.58	0.92 miles per hour Standard Deviation 1.64	0.84 miles per hour Standard Deviation 1.64

SECONDARY outcome

Timeframe: Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

A simulated crash was defined as a collision with an oncoming car or obstacle (e.g., tree) or when the distance to the center line was greater than 18 feet on either side of the road.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 14; 1 Crash, n=33, 28, 33, 28	2 participants	1 participants	0 participants	1 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 14; 2 Crashes, n=33, 28, 33, 28	2 participants	2 participants	0 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 14; 3 Crashes, n=33, 28, 33, 28	0 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 14; 4 Crashes, n=33, 28, 33, 28	0 participants	1 participants	0 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 14; 5 Crashes, n=33, 28, 33, 28	0 participants	1 participants	0 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 14; 13 Crashes, n=33, 28, 33, 28	0 participants	1 participants	0 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 15; 1 Crash, n=33, 28, 31, 28	1 participants	4 participants	1 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 15; 2 Crashes, n=33, 28, 31, 28	0 participants	3 participants	0 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 15; 4 Crashes, n=33, 28, 31, 28	0 participants	2 participants	0 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 15; 13 Crashes, n=33, 28, 31, 28	0 participants	1 participants	0 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 16; 1 Crash, n=30, 28, 33, 28	0 participants	5 participants	3 participants	2 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 16; 3 Crashes, n=30, 28, 33, 28	0 participants	1 participants	2 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 16; 4 Crashes, n=30, 28, 33, 28	0 participants	1 participants	0 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 16; 5 Crashes, n=30, 28, 33, 28	0 participants	0 participants	0 participants	1 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 16; 13 Crashes, n=30, 28, 33, 28	0 participants	0 participants	1 participants	0 participants
Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax) Day 16; 17 Crashes, n=30, 28, 33, 28	0 participants	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Brake reaction time was assessed as the time it took for each participant to move their foot off the accelerator and onto the brake pedal after the appearance of a stop sign on the simulation screen. Change from baseline was calculated as the Day 14, 15, or 16 mean reaction time minus the Baseline (Days -1 and 1) mean reaction time.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=27 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time Day 15, n=32, 25, 30, 25	-0.00 seconds Standard Deviation 0.07	-0.03 seconds Standard Deviation 0.08	-0.01 seconds Standard Deviation 0.15	-0.05 seconds Standard Deviation 0.10
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time Day 16, n=30, 28, 33, 27	-0.04 seconds Standard Deviation 0.10	-0.05 seconds Standard Deviation 0.15	-0.03 seconds Standard Deviation 0.10	-0.03 seconds Standard Deviation 0.16
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time Day 14, n=33, 25, 32, 27	-0.04 seconds Standard Deviation 0.08	-0.07 seconds Standard Deviation 0.09	-0.03 seconds Standard Deviation 0.12	-0.04 seconds Standard Deviation 0.12

SECONDARY outcome

Timeframe: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. Varying numbers of participants did not complete either the pre- or post-drive VAS at either Baseline or the day of assessment; as such, the number of participants analyzed varies by day.

Alertness VAS was completed immediately before and after each simulated driving assessment. Participants indicated their alertness by marking a vertical line on a horizontal scale anchored by responses "extremely sleepy" and "extremely alert." VAS score was determined by measuring the distance in millimeters (mm) from the left hand end of the line to the point the participant marked. Scores ranged from 0-100 mm, with higher scores indicating more alertness and lower scores indicating more sleepiness. Change score was calculated as the Day 14, 15, or 16 VAS score minus the Baseline VAS score.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 14; Pre-Drive, n=33, 28, 32, 28	4.5 millimeters Standard Deviation 22.98	-2.6 millimeters Standard Deviation 25.43	-3.5 millimeters Standard Deviation 29.39	-3.1 millimeters Standard Deviation 20.99
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 14; Post-Drive, n=33, 28, 32, 28	7.7 millimeters Standard Deviation 21.72	3.2 millimeters Standard Deviation 21.76	3.3 millimeters Standard Deviation 21.48	-3.0 millimeters Standard Deviation 22.62
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 14; Post-Pre Drive Difference, n=33,28,32,28	3.1 millimeters Standard Deviation 26.04	5.9 millimeters Standard Deviation 20.69	4.9 millimeters Standard Deviation 25.09	0.1 millimeters Standard Deviation 24.66
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 15; Pre-Drive, n=33, 27, 33, 28	1.5 millimeters Standard Deviation 15.56	0.2 millimeters Standard Deviation 26.98	7.2 millimeters Standard Deviation 21.53	0.4 millimeters Standard Deviation 22.10
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 15; Post-Drive, n=33, 27, 32, 27	-3.2 millimeters Standard Deviation 18.92	-6.1 millimeters Standard Deviation 28.44	4.8 millimeters Standard Deviation 21.08	-3.1 millimeters Standard Deviation 22.97
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 15; Post-Pre Drive Difference, n=33,27,32,27	-4.7 millimeters Standard Deviation 22.22	-6.3 millimeters Standard Deviation 24.55	-2.2 millimeters Standard Deviation 27.45	-3.7 millimeters Standard Deviation 33.84
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 16; Pre-Drive, n=32, 28, 33, 28	6.3 millimeters Standard Deviation 23.44	0.8 millimeters Standard Deviation 32.79	-8.8 millimeters Standard Deviation 27.61	-11.8 millimeters Standard Deviation 24.00
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 16; Post-Drive, n=31, 28, 33, 28	14.3 millimeters Standard Deviation 22.23	-3.6 millimeters Standard Deviation 32.01	-7.5 millimeters Standard Deviation 26.17	-14.0 millimeters Standard Deviation 29.25
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score Day 16; Post-Pre Drive Difference, n=31,28,33,28	7.7 millimeters Standard Deviation 22.38	-4.5 millimeters Standard Deviation 36.14	1.3 millimeters Standard Deviation 34.13	-2.3 millimeters Standard Deviation 23.91

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 14

Population: Modified Intent-to-Treat (MITT) Population

The Epworth Sleepiness Scale (ESS) is a questionnaire designed to evaluate daytime sleepiness. Participants were asked to rate how likely they were to doze or fall asleep during 8 activities on a scale of 0 ("would never do") to 3 ("high chance of dozing"). The total score ranges from 0-24, with a score greater than 10 representing excessive daytime sleepiness (an increased chance of dozing). Change from baseline was calculated as the Day 14 total score minus the Baseline total score.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score	-2.6 scores on a scale Standard Deviation 3.22	-2.3 scores on a scale Standard Deviation 5.61	-2.4 scores on a scale Standard Deviation 5.04	-2.4 scores on a scale Standard Deviation 4.88

SECONDARY outcome

Timeframe: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

The BAC was designed as a comprehensive measure of cognitive function, including 6 individual tests: Verbal Memory Recall, Digit Sequencing, Token Motor Task, Verbal Fluency, Symbol Coding, and Tower of London. The composite/total BAC score is calculated by scoring each individual test, comparing each score to a healthy control sample (matched for sex and age category) to create z-scores, summing the z-scores, and rescaling the sum. The composite score range is -2127.8 to 1878.8, with higher scores indicating better cognition.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score Day 15, n=33, 28, 33, 28	4.8 scores on a scale Standard Deviation 5.39	3.4 scores on a scale Standard Deviation 4.59	0.2 scores on a scale Standard Deviation 6.61	4.8 scores on a scale Standard Deviation 4.66
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score Day 14, n=33, 28, 33, 28	4.6 scores on a scale Standard Deviation 5.64	5.3 scores on a scale Standard Deviation 7.01	5.3 scores on a scale Standard Deviation 6.88	7.0 scores on a scale Standard Deviation 6.25
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score Day 16, n=32, 28, 33, 28	7.2 scores on a scale Standard Deviation 7.24	9.1 scores on a scale Standard Deviation 8.98	7.1 scores on a scale Standard Deviation 8.34	10.7 scores on a scale Standard Deviation 6.05

SECONDARY outcome

Timeframe: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Participants were presented with 15 words and asked to recall as many as possible; the procedure was repeated 5 times. The total number of words recalled correctly across the 5 administrations of the list was the participant's Verbal Memory Recall score (range: 0-75). The scaled test score was calculated as ((BAC component raw test score - healthy control sample test mean)/healthy control sample test standard deviation); a healthy control sample was matched to the participant's sex and age category. The scaled test score range is -7.37 to 4.86; higher scaled scores indicate better cognition.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score Day 14, n=33, 28, 33, 28	0.1 scores on a scale Standard Deviation 0.77	0.1 scores on a scale Standard Deviation 0.83	0.2 scores on a scale Standard Deviation 0.82	0.1 scores on a scale Standard Deviation 0.94
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score Day 15, n=33, 28, 33, 28	0.2 scores on a scale Standard Deviation 0.63	0.1 scores on a scale Standard Deviation 0.75	-0.0 scores on a scale Standard Deviation 0.93	0.1 scores on a scale Standard Deviation 0.80
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score Day 16, n=32, 28, 33, 28	-0.2 scores on a scale Standard Deviation 0.78	-0.1 scores on a scale Standard Deviation 0.88	0.1 scores on a scale Standard Deviation 0.97	0.0 scores on a scale Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Participants (par.) were presented with sets of numbers of increasing length and asked to tell the experimenter the numbers in order from lowest to highest. The task has 7 levels; the first level had 2 digits in the set (e.g., 5, 2); the second level had 3 digits in the set, etc. The number of times the par. correctly arranged the numbers was recorded as the score for each level. The DSS is the sum of the 7 level scores (range: 0-28). The scaled test score was calculated as indicated for the Verbal Memory Test and ranges from -6.68 to 2.73; higher scaled scores indicate better cognition.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS) Day 14, n=33, 28, 33, 28	0.3 scores on a scale Standard Deviation 0.84	0.2 scores on a scale Standard Deviation 0.90	0.4 scores on a scale Standard Deviation 0.75	0.3 scores on a scale Standard Deviation 0.80
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS) Day 15, n=33, 28, 33, 28	0.2 scores on a scale Standard Deviation 0.83	0.3 scores on a scale Standard Deviation 0.86	-0.2 scores on a scale Standard Deviation 0.72	0.1 scores on a scale Standard Deviation 0.69
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS) Day 16, n=32, 28, 33, 28	0.3 scores on a scale Standard Deviation 0.79	0.4 scores on a scale Standard Deviation 0.66	0.5 scores on a scale Standard Deviation 0.73	0.7 scores on a scale Standard Deviation 0.75

SECONDARY outcome

Timeframe: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Participants were given 100 plastic tokens and asked to place them in a container, 2 at a time, as quickly as possible for 60 seconds. The number of tokens correctly placed in the container was the Token Motor Task score (range: 0-100). The BAC was conducted prior to each simulated driving test. The Token Motor Task scaled test score was calculated as indicated for the Verbal Memory Test. Change from baseline was calculated as the Day composite score minus the Baseline composite score. The scaled test score range is -6.95 to 3.35, with higher scaled scores indicating better cognition.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score Day 14, n=33, 28, 33, 28	0.2 scores on a scale Standard Deviation 1.03	0.4 scores on a scale Standard Deviation 1.06	0.2 scores on a scale Standard Deviation 1.29	0.3 scores on a scale Standard Deviation 0.89
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score Day 15, n=33, 28, 33, 28	0.4 scores on a scale Standard Deviation 1.12	-0.0 scores on a scale Standard Deviation 0.93	-0.2 scores on a scale Standard Deviation 0.86	0.2 scores on a scale Standard Deviation 0.67
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score Day 16, n=32, 28, 33, 28	0.4 scores on a scale Standard Deviation 1.08	0.4 scores on a scale Standard Deviation 1.04	0.1 scores on a scale Standard Deviation 1.34	0.4 scores on a scale Standard Deviation 1.09

SECONDARY outcome

Timeframe: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Verbal Fluency included one semantic fluency and two letter fluency tasks. Participants were given 60 seconds to name as many words as possible within a given semantic category (supermarket items), and in two separate trials, participants were given 60 seconds to generate as many words as possible that began with a given letter. The total number of words from all of the 3 trials was the Verbal Fluency score (range: 0-150). The scaled test score was calculated as indicated for the Verbal Memory Test. The scaled test score range is -5 to 10.83; higher scaled scores indicate better cognition.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score Day 14, n=33, 28, 33, 28	0.2 scores on a scale Standard Deviation 0.91	0.5 scores on a scale Standard Deviation 0.84	0.4 scores on a scale Standard Deviation 0.76	0.6 scores on a scale Standard Deviation 0.68
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score Day 15, n=33, 28, 33, 28	0.4 scores on a scale Standard Deviation 0.65	0.1 scores on a scale Standard Deviation 0.65	0.2 scores on a scale Standard Deviation 0.68	0.4 scores on a scale Standard Deviation 0.87
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score Day 16, n=32, 28, 33, 28	0.7 scores on a scale Standard Deviation 1.04	0.7 scores on a scale Standard Deviation 0.83	0.4 scores on a scale Standard Deviation 0.97	0.9 scores on a scale Standard Deviation 0.98

SECONDARY outcome

Timeframe: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Participants were given a list of numbers (numerals 1-9) that were each associated with a unique symbol. Participants decoded a list of 110 symbols as quickly as possible in 90 seconds. The total number of symbols correctly decoded was the Symbol Coding Score (range: 0-110). The Symbol Coding scaled test score was calculated as indicated for the Verbal Memory Test. Change from baseline was calculated as the Day composite score minus the Baseline composite score. The scaled test score range is -7 to 10.08, with higher scaled scores indicating better cognition.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score Day 14, n=33, 28, 33, 28	0.6 scores on a scale Standard Deviation 0.57	0.6 scores on a scale Standard Deviation 0.87	0.5 scores on a scale Standard Deviation 0.72	0.6 scores on a scale Standard Deviation 0.85
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score Day 15, n=33, 28, 33, 28	0.5 scores on a scale Standard Deviation 0.85	0.5 scores on a scale Standard Deviation 0.78	-0.0 scores on a scale Standard Deviation 1.04	0.4 scores on a scale Standard Deviation 0.78
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score Day 16, n=32, 28, 33, 28	1.3 scores on a scale Standard Deviation 0.92	1.4 scores on a scale Standard Deviation 1.28	1.0 scores on a scale Standard Deviation 0.95	1.3 scores on a scale Standard Deviation 0.81

SECONDARY outcome

Timeframe: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. The number of participants assessed at each study day varies due to incomplete/missing data.

Participants (par.) were asked to look at 2 pictures simultaneously; each picture showed 3 different colored balls arranged on 3 pegs. Par. were to estimate the number of times the balls in 1 picture would have to be moved to make the arrangement of balls identical to that of the second picture. Par. were allowed 20 seconds to respond to each pair of pictures. The number of correct items was the TOL Score (range: 0-22). The TOL scaled test score was calculated as indicated for the Verbal Memory Test. The scaled test score range is -7.53 to 2.76; higher scaled scores indicate better cognition.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=33 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=28 Participants Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score Day 14, n=33, 28, 33, 28	0.3 scores on a scale Standard Deviation 0.59	0.2 scores on a scale Standard Deviation 1.03	0.3 scores on a scale Standard Deviation 1.17	0.5 scores on a scale Standard Deviation 0.95
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score Day 15, n=33, 28, 33, 28	0.2 scores on a scale Standard Deviation 0.65	0.3 scores on a scale Standard Deviation 0.90	0.4 scores on a scale Standard Deviation 0.89	0.5 scores on a scale Standard Deviation 1.30
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score Day 16, n=32, 28, 33, 28	0.1 scores on a scale Standard Deviation 0.73	0.5 scores on a scale Standard Deviation 0.91	0.5 scores on a scale Standard Deviation 0.96	0.6 scores on a scale Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group.

The IRLS Rating scale is a measure of RLS disease severity and reflects the participant-reported assessment of primary sensory and motor features and associated sleep problems in RLS. Items are included that assess the impact of symptoms on participants' mood, daily life, and activities. The total score ranges from 0-40 points, with 40 being the most severe. The scale assesses symptoms over the week prior to measurement.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Mean Change From Baseline (Day -1) at Day 14 in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score	-7.6 scores on a scale Standard Deviation 7.63	-12.4 scores on a scale Standard Deviation 9.93	-13.1 scores on a scale Standard Deviation 8.09	—

SECONDARY outcome

Timeframe: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group.

The CGI scale is a widely used tool designed to allow clinicians to rate the severity of illness and the change of the disease severity over time based on a seven-point rating scale, with a score of 1 being "very much improved" and a score of 7 being "very much worse" compared to baseline.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Very Much Improved, score of 1	7 participants	10 participants	15 participants	—
Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Much Improved, score of 2	15 participants	7 participants	8 participants	—
Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Minimally Improved, score of 3	19 participants	7 participants	6 participants	—
Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 No Change, score of 4	15 participants	4 participants	4 participants	—
Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Minimally Worse, score of 5	4 participants	0 participants	0 participants	—
Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Much Worse, score of 6	1 participants	0 participants	0 participants	—
Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Very Much Worse, score of 7	0 participants	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group.

The investigator-rated CGI-I is a clinician-rated assessment designed to allow clinicians to rate the change of their participant's disease severity over time based on a seven-point scale, with a score of 1 being "very much improved," and a score of 7 being "very much worse" compared to baseline. For this endpoint, "response" was defined as a rating of "very much improved" or "much improved" (score of 1 or 2 on the scale) compared to baseline.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Number of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated CGI-I at Day 14	22 participants	17 participants	23 participants	—

SECONDARY outcome

Timeframe: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group.

The participant-rated CGI-I scale is a self-rated assessment designed to allow participants to rate the change of their disease severity over time based on a seven-point scale, with a score of 1 being "very much improved" and a score of 7 being "very much worse".

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Very Much Improved, score of 1	7 participants	9 participants	14 participants	—
Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Much Improved, score of 2	16 participants	11 participants	9 participants	—
Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Minimally Improved, score of 3	14 participants	3 participants	6 participants	—
Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 No Change, score of 4	17 participants	3 participants	4 participants	—
Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Minimally Worse, score of 5	5 participants	2 participants	0 participants	—
Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Much Worse, score of 6	2 participants	0 participants	0 participants	—
Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14 Very Much Worse, score of 7	0 participants	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group.

The participant-rated CGI-I is a self-rated assessment designed to allow participants to rate the change of their disease severity over time based on a seven-point scale, with a score of 1 being "very much improved," and a score of 7 being "very much worse." "Response" was defined as a rating of "very much improved" or "much improved" (score of 1 or 2 on the scale).

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Number of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Day 14	23 participants	20 participants	23 participants	—

SECONDARY outcome

Timeframe: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the

The 24-Hour RLS Record is a diary in which participants report the presence and severity of RLS symptoms (none, mild, moderate, or severe) for a 24-hour period, in 30-min increments beginning at 8AM on the day prior to the visit. For Arms 2 and 3, upper limits of the confidence intervals are not available, as they are beyond the 24-hour time frame.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Median Time to Onset of a Participant's First RLS Symptoms Using the 24-hour RLS Symptom Record at Day 14	7.0 participants Interval 3.5 to 13.0	14.3 participants Interval 7.5 to The upper limit of the confidence interval is not available, as it is beyond the 24-hour time frame.	15.5 participants Interval 13.5 to The upper limit of the confidence interval is not available, as it is beyond the 24-hour time frame.	—

SECONDARY outcome

Timeframe: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the

The 24-Hour RLS Record is a diary in which participants report the presence and severity of RLS symptoms (none, mild, moderate, or severe) for a 24-hour period, in 30-min increments beginning at 8AM on the day prior to the visit.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Percentage of Participants With no Reported RLS Symptoms During the 24-hour RLS Record at Day 14	9.84 percentage of participants	35.71 percentage of participants	42.42 percentage of participants	—

SECONDARY outcome

Timeframe: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group.

The 24-Hour RLS Record is a diary in which participants report the presence and severity of RLS symptoms (none, mild, moderate, or severe) for a 24-hour period, in 30-minute increments. The period was divided into 7 four-hour intervals (8 AM to 12 PM, 12 PM to 4 PM, 4 PM to 8 PM, 6 PM to 10 PM, 8 PM to 12 Midnight, Midnight to 4 AM, and 4 AM to 8 AM).

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14 8 AM to 12 PM	37 participants	21 participants	27 participants	—
Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14 12 PM to 4 PM	35 participants	20 participants	23 participants	—
Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14 4 PM to 8 PM	36 participants	19 participants	26 participants	—
Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14 6 PM to 10 PM	27 participants	18 participants	23 participants	—
Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14 8 PM to 12 AM	18 participants	13 participants	18 participants	—
Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14 12 AM to 4 AM	24 participants	17 participants	24 participants	—
Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14 4 AM to 8 AM	39 participants	23 participants	26 participants	—

SECONDARY outcome

Timeframe: Day 14

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group.

The PSQ is designed to evaluate sleep quality, ability to function, and the degree to which RLS symptoms interfere with sleep.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 Sleep Quality: Excellent	9 participants	5 participants	14 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 Sleep Quality: Reasonable	31 participants	18 participants	17 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 Sleep Quality: Poor	21 participants	5 participants	2 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 Ability to Function: Excellent	8 participants	6 participants	11 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 Ability to Function: Good	32 participants	17 participants	18 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 Ability to Function: Moderate	20 participants	5 participants	4 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 Ability to Function: Poor	1 participants	0 participants	0 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 0 Nights with RLS Symptoms	8 participants	8 participants	10 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 1-2 Nights with RLS Symptoms	12 participants	7 participants	9 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 3-4 Nights with RLS Symptoms	17 participants	6 participants	8 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 5-6 Nights with RLS Symptoms	13 participants	1 participants	3 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 7 Nights with RLS Symptoms	11 participants	6 participants	3 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 0 Awakenings/Night due to RLS	10 participants	7 participants	8 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 1-2 Wakenings/Night due to RLS	41 participants	18 participants	23 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 3-4 Awakenings/Night due to RLS	8 participants	2 participants	1 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 5+ Awakenings/Night due to RLS	2 participants	1 participants	1 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 0 Hours Awake/Night due to RLS	53 participants	23 participants	31 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 <1 Hour Awake/Night due to RLS	3 participants	4 participants	0 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 1-<2 Hours Awake/Night due to RLS	3 participants	0 participants	0 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 2-<3 Hours Awake/Night due to RLS	2 participants	1 participants	2 participants	—
Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14 3+ Hours Awake/Night due to RLS	0 participants	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Baseline (Days -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group. The number of participants assessed for each PghSD question at each study day varies due to incomplete/missing data.

The PghSD assessed participant's previous night's sleep. Change from baseline was calculated as the Day 14 (in the evening), 15 (in the morning), and 16 (at Tmax of GEn and DPH) value minus the Baseline (Days -1 and 1) value. Latency to sleep onset (time to fall asleep) and wake time after sleep onset are expressed in minutes.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items Day 14; Latency to Sleep Onset, n=61, 28, 33	-8.1 minutes Standard Deviation 54.74	-3.2 minutes Standard Deviation 62.96	-25.7 minutes Standard Deviation 60.32	—
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items Day 14; Wake Time After Sleep Onset, n=59, 26, 33	-14.0 minutes Standard Deviation 45.46	-23.3 minutes Standard Deviation 41.11	-26.9 minutes Standard Deviation 45.18	—
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items Day 15; Latency to Sleep Onset n=61, 28, 33	-8.7 minutes Standard Deviation 57.28	-14.9 minutes Standard Deviation 54.05	-35.8 minutes Standard Deviation 59.02	—
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items Day 15; Wake Time After Sleep Onset, n=60, 28, 33	4.9 minutes Standard Deviation 61.11	-30.8 minutes Standard Deviation 51.97	-14.8 minutes Standard Deviation 64.07	—
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items Day 16; Latency to Sleep Onset, n=60, 28, 23	-17.3 minutes Standard Deviation 46.6	-3.3 minutes Standard Deviation 55.67	-19.3 minutes Standard Deviation 52.76	—
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items Day 16; Wake Time After Sleep Onset, n=59, 26, 33	-15.8 minutes Standard Deviation 55.44	-26.3 minutes Standard Deviation 29.50	-9.9 minutes Standard Deviation 60.58	—

SECONDARY outcome

Timeframe: Baseline (Days -1 and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group. The number of participants assessed for each PghSD question at each study day varies due to incomplete/missing data.

The PghSD assessed a participant's previous night's sleep. Change from baseline was calculated as the Day 14 (in the evening), 15 (in the morning after dose), and 16 (at Tmax)value minus the Baseline (Days -1 and 1) value. Total sleep time is expressed in hours.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item Day 14, n=59, 26, 33	0.3 hours Standard Deviation 1.60	0.2 hours Standard Deviation 1.82	1.0 hours Standard Deviation 2.39	—
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item Day 15, n=60, 28, 33	-0.2 hours Standard Deviation 2.10	0.2 hours Standard Deviation 1.24	0.3 hours Standard Deviation 1.54	—
Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item Day 16, n=59, 26, 33	0.5 hours Standard Deviation 1.82	0.3 hours Standard Deviation 1.32	0.4 hours Standard Deviation 1.91	—

SECONDARY outcome

Timeframe: Baseline (Day -1and 1) and Days 14, 15, and 16

Population: Modified Intent-to-Treat (MITT) Population. Participants in the "GEn placebo and DPH placebo" and the "GEn placebo and DPH 50 mg on Day 16" arms have been combined into the "GEn placebo and DPH" group. The number of participants assessed for each PghSD question at each study day varies due to incomplete/missing data.

The PghSD assessed a participant's previous night's sleep. Sleep quality was assessed using a Visual Analogue Scale (VAS). Participants indicated their sleep quality by marking a vertical line on a horizontal scale anchored by responses "very bad" and "very good." VAS score was determined by measuring the distance in millimeters (mm) from the left hand end of the line to the point that the participant marked. Scores ranged from 0 to 100 mm with higher scores indicating better sleep quality and lower scores indicating worse sleep quality.

Outcome measures

Measure	GEn Placebo and DPH Placebo n=61 Participants Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=28 Participants Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=33 Participants Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality Day 14, n=61, 28, 33	21.2 millimeters Standard Deviation 29.47	29.9 millimeters Standard Deviation 30.76	35.1 millimeters Standard Deviation 28.84	—
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality Day 15, n=61, 28, 33	11.8 millimeters Standard Deviation 27.30	24.6 millimeters Standard Deviation 29.15	18.0 millimeters Standard Deviation 24.82	—
Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality Day 16, n=59, 28, 33	20.7 millimeters Standard Deviation 25.01	27.4 millimeters Standard Deviation 24.11	16.7 millimeters Standard Deviation 28.86	—

Adverse Events

GEn Placebo and DPH Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

GEn 1200 mg and DPH Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

GEn 1800 mg and DPH Placebo

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

GEn Placebo and DPH 50 mg on Day 16

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	GEn Placebo and DPH Placebo n=34 participants at risk Oral gabapentin enacarbil (GEn) placebo taken once daily. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of diphenhydramine (DPH) placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.	GEn 1200 mg and DPH Placebo n=31 participants at risk Oral GEn (XP13512/GSK1838262) 1200 milligrams (mg) taken once daily. Days 1 to 3: one extended release (ER) tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: two ER tablets (600 mg GEn each) and one placebo tablet. On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: one ER tablet (600 mg GEn) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn 1800 mg and DPH Placebo n=34 participants at risk Oral GEn (XP13512/GSK1838262) 1800 mg taken once daily. Days 1 to 3: one ER tablet (600 mg GEn). Days 4 to 7: two ER tablets (600 mg GEn each). Days 8 to 16: three ER tablets (600 mg GEn each). On Day 16, participants also took two capsules of DPH placebo. On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two ER tablets (600 mg GEn each) and one placebo tablet. Days 21 to 23: one ER tablet (600 mg GEn).	GEn Placebo and DPH 50 mg on Day 16 n=30 participants at risk Oral GEn placebo taken once daily and oral DPH 50 mg taken once on Day 16. Days 1 to 3: one placebo tablet. Days 4 to 7: two placebo tablets. Days 8 to 16: three placebo tablets. On Day 16, participants also took two capsules of DPH (25 mg DPH each). On Day 17, participants entered a 7-day Taper Period. Days 17 to 20: two placebo tablets. Days 21 to 23: one placebo tablet.
Nervous system disorders Somnolence	2.9% 1/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	25.8% 8/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	38.2% 13/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	6.7% 2/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Nervous system disorders Headache	8.8% 3/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	16.1% 5/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	11.8% 4/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	13.3% 4/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Nervous system disorders Dizziness	8.8% 3/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	12.9% 4/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	11.8% 4/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	6.7% 2/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
General disorders Fatigue	2.9% 1/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	6.5% 2/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	11.8% 4/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	13.3% 4/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Gastrointestinal disorders Nausea	2.9% 1/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	6.5% 2/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	2.9% 1/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	6.7% 2/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	6.5% 2/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	10.0% 3/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Nervous system disorders Balance Disorder	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	6.5% 2/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	5.9% 2/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Gastrointestinal disorders Diarrhoea	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	3.2% 1/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	5.9% 2/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Gastrointestinal disorders Dry Mouth	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	5.9% 2/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	3.3% 1/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Ear and labyrinth disorders Motion Sickness	2.9% 1/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	5.9% 2/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Nervous system disorders Restless Legs Syndrome	8.8% 3/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Musculoskeletal and connective tissue disorders Back Pain	5.9% 2/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
General disorders Feeling Abnormal	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	5.9% 2/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/31 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	0.00% 0/34 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.	6.7% 2/30 • Treatment-Emergent Adverse Events (TEAEs): First dose of randomized study medication through end of Taper Phase (Day 23). Any Serious Adverse Event (SAE) reported up to 30 days after last dose was also reported. TEAEs were AEs reported in the Safety Population from the time the first dose of study drug was administered to the end of the Taper Phase (Day 23). AEs were considered TEAEs if the onset date or a reported change in severity (for ongoing events) occurred after Randomization.

Additional Information

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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.
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