NCT03053427

A Study of Oral Dosing of Gabapentin Enacarbil in Japanese Restless Legs Syndrome Patients

Completed Phase 4 Results posted Last updated 12 December 2024

What this trial tests

Phase 4 trial testing Placebo in Restless Legs Syndrome (RLS) in 375 participants. Completed in 25 June 2018.

Timeline

30 March 2017

Primary endpoint
25 June 2018

25 June 2018

Quick facts

Lead sponsor	Astellas Pharma Inc
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	375
Start date	30 March 2017
Primary completion	25 June 2018
Estimated completion	25 June 2018
Sites	46 locations across Japan

Drugs / interventions tested

• Placebo
• Gabapentin enacarbil (GABAPENTIN ENACARBIL) — full drug profile →

Conditions studied

• Restless Legs Syndrome (RLS) — all drugs for Restless Legs Syndrome (RLS) →

Sponsor

Astellas Pharma Inc — full company profile →

Who can join

Adults 20 to 80, any sex, with Restless Legs Syndrome (RLS). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in International Restless Legs Syndrome Rating Scale (IRLS) Score at Week 12 Primary · Baseline and week 12

The IRLS consisted of 10-item scale for assessing severity of restless legs syndrome (RLS) with each item ranging from 0 (no symptoms) to 4 (very severe symptoms). The total IRLS score ranges from 0 to 40. Higher IRLS score indicated greater disease activity. Mixed Model of Repeated Measurements (MMRM) model with compound symmetry as a covariance structure was used. The explanatory variables of the model included treatment group, IRLS score at baseline, age category, estimated creatinine clearance category, time point, and interaction of treatment group and time point.

Group	Value	95% CI
Placebo	-10.5	-11.4 – -9.5
Gabapentin Enacarbil	-11.7	-12.6 – -10.7

Change From Baseline in IRLS Score at Each Time Point Secondary · Baseline and weeks 1, 2, 4, 6, 8, 10, 12 and EoT (week 12)

ANCOVA model with the baseline value as a covariate was used.

Week 1

Group	Value	95% CI
Placebo	-3.1	-3.9 – -2.3
Gabapentin Enacarbil	-4.2	-5.0 – -3.4

Week 2

Group	Value	95% CI
Placebo	-4.3	-5.2 – -3.4
Gabapentin Enacarbil	-5.8	-6.7 – -4.9

Week 4

Group	Value	95% CI
Placebo	-6.0	-6.9 – -5.0
Gabapentin Enacarbil	-7.5	-8.4 – -6.5

Week 6

Group	Value	95% CI
Placebo	-7.4	-8.4 – -6.3
Gabapentin Enacarbil	-8.8	-9.9 – -7.8

Week 8

Group	Value	95% CI
Placebo	-8.8	-9.8 – -7.8
Gabapentin Enacarbil	-9.8	-10.8 – -8.8

Week 10

Group	Value	95% CI
Placebo	-9.6	-10.6 – -8.5
Gabapentin Enacarbil	-11.2	-12.3 – -10.2

Week 12

Group	Value	95% CI
Placebo	-10.5	-11.6 – -9.4
Gabapentin Enacarbil	-11.9	-13.0 – -10.8

EoT

Group	Value	95% CI
Placebo	-10.2	-11.4 – -9.1
Gabapentin Enacarbil	-11.1	-12.2 – -9.9

Percentage of Participants With an Investigator-rated Clinical Global Impression (ICGI) Response Secondary · EoT (week 12)

ICGI was assessed by 7-point ordinate scale. Participants who were "Very much improved" or "Much improved" were defined as responders.

Group	Value	95% CI
Placebo	53.2	45.8 – 60.6
Gabapentin Enacarbil	57.4	50.0 – 64.6

Percentage of Participants With a Patient-rated Clinical Global Impression (PCGI) Response Secondary · EoT (week 12)

PCGI was assessed by 7-point ordinate scale. Participants who were "Very much improved" or "Much improved" were defined as responders.

Group	Value	95% CI
Placebo	50.5	43.1 – 57.9
Gabapentin Enacarbil	56.4	49.0 – 63.6

Change From Baseline in Pittsburgh Sleep Quality Index Total Score (PSQI) Secondary · Baseline and EoT (week 12)

The self-rated items of the PSQI generate seven component scores (range of subscale scores, 0-3). The sum of these seven component scores yielded one global score of subjective sleep quality (range, 0-21). Higher scores represent poorer subjective sleep. ANCOVA model with the baseline value as a covariate was used.

Group	Value	95% CI
Placebo	-1.7	-2.1 – -1.4
Gabapentin Enacarbil	-1.7	-2.1 – -1.4

Change From Baseline in Athens Insomnia Scale Secondary · Baseline and EoT (week 12)

Athens Insomnia Scale consisted of 8-item scale (range of subscale scores, 0-3). The scale range of Athens Insomnia was 0-24. Higher scores represent poorer sleep quality. ANCOVA model with the baseline value as a covariate was used.

Group	Value	95% CI
Placebo	-2.5	-2.9 – -2.0
Gabapentin Enacarbil	-2.5	-2.9 – -2.0

Change From Baseline in Restless Legs Syndrome (RLS) Pain Score Secondary · Baseline and EoT (week 12)

The scale range of RLS pain score was 0-10. Higher scores represent greater RLS pain intensity. ANCOVA model with the baseline value as a covariate was used.

Group	Value	95% CI
Placebo	-0.9	-1.2 – -0.7
Gabapentin Enacarbil	-1.0	-1.2 – -0.7

Change From Baseline in Health Status Score of EuroQol-5 Dimension-5 Level (EQ-5D-5L) Secondary · Baseline and EoT (week 12)

Health status was assessed by general visual analog scale (VAS). The VAS ranges from 0 (worst health status) and 100 (best health status).

Group	Value	95% CI
Placebo	2.7	± 16.7
Gabapentin Enacarbil	4.2	± 15.3

Number of Participants With Adverse Events Secondary · From first dose of study drug up to week 13

Treatment-emergent adverse events (TEAE) was defined as an adverse event (AE) with onset after the start of the run-in period. A drug-related TEAE was a TEAE with at least a possible relationship to the study drug as assessed by the investigator. Serious TEAE was an AE considered serious.

Any TEAEs

Group	Value	95% CI
Placebo	71
Gabapentin Enacarbil	94

Drug-related TEAEs

Group	Value	95% CI
Placebo	36
Gabapentin Enacarbil	60

TEAEs leading to death

Group	Value	95% CI
Placebo	0
Gabapentin Enacarbil	0

Serious TEAEs

Group	Value	95% CI
Placebo	0
Gabapentin Enacarbil	3

Drug-related serious TEAEs

Group	Value	95% CI
Placebo	0
Gabapentin Enacarbil	0

TEAEs leading to discontinuation of study drug

Group	Value	95% CI
Placebo	4
Gabapentin Enacarbil	4

Drug-related TEAEs leading to disc. of study drug

Group	Value	95% CI
Placebo	3
Gabapentin Enacarbil	4

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to week 13. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/186 (0%)

Deaths: 0/186

Gabapentin Enacarbil

Serious: 3/189 (2%)

Deaths: 0/189

Serious adverse events (3 terms)

Reaction	System	Placebo	Gabapentin Enacarbil
Colitis ischaemic	Gastrointestinal disorders	—	—
Anaphylactic reaction	Immune system disorders	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Placebo	Gabapentin Enacarbil
Somnolence neonatal	Nervous system disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Dizziness	Nervous system disorders	—	—

Most-reported serious reactions: Colitis ischaemic, Anaphylactic reaction, Femur fracture.

Data from ClinicalTrials.gov NCT03053427 adverse events section.

Sponsor's own description

The objective of this study was to assess the efficacy of once-daily oral administration of gabapentin enacarbil versus placebo, based on the change in International Restless Legs Syndrome Rating Scale (IRLS) score in participants with moderate-to-severe idiopathic restless legs syndrome. This study also assessed the safety of Gabapentin enacarbil.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.