Trial Outcomes & Findings for A Study of Oral Dosing of Gabapentin Enacarbil in Japanese Restless Legs Syndrome Patients (NCT NCT03053427)
NCT ID: NCT03053427
Last Updated: 2024-12-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
375 participants
Primary outcome timeframe
Baseline and week 12
Results posted on
2024-12-12
Participant Flow
Participants with moderate to severe idiopathic restless legs syndrome were enrolled in 51 study sites in Japan.
Participants received single-blind placebo for 1 week (run-in period). Subsequently, eligible participants were randomized to receive gabapentin enacarbil or placebo orally once daily after dinner for 12 weeks (treatment period).
Participant milestones
| Measure |
Placebo
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
186
|
189
|
|
Overall Study
COMPLETED
|
173
|
173
|
|
Overall Study
NOT COMPLETED
|
13
|
16
|
Reasons for withdrawal
| Measure |
Placebo
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
4
|
|
Overall Study
Lack of Efficacy
|
1
|
3
|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
|
Overall Study
Worsening of the target disease
|
0
|
1
|
|
Overall Study
Protocol Deviation
|
3
|
3
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Miscellaneous
|
0
|
1
|
Baseline Characteristics
Data were provided for the full analysis set (FAS), which included all participants who received study drug and were evaluated for at least one efficacy (either primary or secondary) endpoint during the treatment period.
Baseline characteristics by cohort
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=189 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
Total
n=375 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.2 year
STANDARD_DEVIATION 12.4 • n=186 Participants
|
51.1 year
STANDARD_DEVIATION 13.5 • n=189 Participants
|
51.6 year
STANDARD_DEVIATION 13.0 • n=375 Participants
|
|
Sex: Female, Male
Female
|
79 Participants
n=186 Participants
|
90 Participants
n=189 Participants
|
169 Participants
n=375 Participants
|
|
Sex: Female, Male
Male
|
107 Participants
n=186 Participants
|
99 Participants
n=189 Participants
|
206 Participants
n=375 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=186 Participants
|
0 Participants
n=189 Participants
|
0 Participants
n=375 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
186 Participants
n=186 Participants
|
189 Participants
n=189 Participants
|
375 Participants
n=375 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=186 Participants
|
0 Participants
n=189 Participants
|
0 Participants
n=375 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=186 Participants
|
0 Participants
n=189 Participants
|
0 Participants
n=375 Participants
|
|
Race (NIH/OMB)
Asian
|
186 Participants
n=186 Participants
|
189 Participants
n=189 Participants
|
375 Participants
n=375 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=186 Participants
|
0 Participants
n=189 Participants
|
0 Participants
n=375 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=186 Participants
|
0 Participants
n=189 Participants
|
0 Participants
n=375 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=186 Participants
|
0 Participants
n=189 Participants
|
0 Participants
n=375 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=186 Participants
|
0 Participants
n=189 Participants
|
0 Participants
n=375 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=186 Participants
|
0 Participants
n=189 Participants
|
0 Participants
n=375 Participants
|
|
International Restless Legs Syndrome Rating Scale (IRLS) score
|
23.8 units on a scale
STANDARD_DEVIATION 5.4 • n=186 Participants • Data were provided for the full analysis set (FAS), which included all participants who received study drug and were evaluated for at least one efficacy (either primary or secondary) endpoint during the treatment period.
|
23.7 units on a scale
STANDARD_DEVIATION 5.2 • n=188 Participants • Data were provided for the full analysis set (FAS), which included all participants who received study drug and were evaluated for at least one efficacy (either primary or secondary) endpoint during the treatment period.
|
23.7 units on a scale
STANDARD_DEVIATION 5.3 • n=374 Participants • Data were provided for the full analysis set (FAS), which included all participants who received study drug and were evaluated for at least one efficacy (either primary or secondary) endpoint during the treatment period.
|
PRIMARY outcome
Timeframe: Baseline and week 12Population: Full Analysis Set (FAS) consisted of all participants who received the study drug for the treatment period and were evaluated for at least one efficacy (either primary or secondary) endpoint during the treatment period.
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.
Outcome measures
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=188 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Change From Baseline in International Restless Legs Syndrome Rating Scale (IRLS) Score at Week 12
|
-10.5 units on a scale
Interval -11.4 to -9.5
|
-11.7 units on a scale
Interval -12.6 to -10.7
|
SECONDARY outcome
Timeframe: Baseline and weeks 1, 2, 4, 6, 8, 10, 12 and EoT (week 12)Population: FAS.
ANCOVA model with the baseline value as a covariate was used.
Outcome measures
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=188 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Change From Baseline in IRLS Score at Each Time Point
Week 1
|
-3.1 units on a scale
Interval -3.9 to -2.3
|
-4.2 units on a scale
Interval -5.0 to -3.4
|
|
Change From Baseline in IRLS Score at Each Time Point
Week 2
|
-4.3 units on a scale
Interval -5.2 to -3.4
|
-5.8 units on a scale
Interval -6.7 to -4.9
|
|
Change From Baseline in IRLS Score at Each Time Point
Week 4
|
-6.0 units on a scale
Interval -6.9 to -5.0
|
-7.5 units on a scale
Interval -8.4 to -6.5
|
|
Change From Baseline in IRLS Score at Each Time Point
Week 6
|
-7.4 units on a scale
Interval -8.4 to -6.3
|
-8.8 units on a scale
Interval -9.9 to -7.8
|
|
Change From Baseline in IRLS Score at Each Time Point
Week 8
|
-8.8 units on a scale
Interval -9.8 to -7.8
|
-9.8 units on a scale
Interval -10.8 to -8.8
|
|
Change From Baseline in IRLS Score at Each Time Point
Week 10
|
-9.6 units on a scale
Interval -10.6 to -8.5
|
-11.2 units on a scale
Interval -12.3 to -10.2
|
|
Change From Baseline in IRLS Score at Each Time Point
Week 12
|
-10.5 units on a scale
Interval -11.6 to -9.4
|
-11.9 units on a scale
Interval -13.0 to -10.8
|
|
Change From Baseline in IRLS Score at Each Time Point
EoT
|
-10.2 units on a scale
Interval -11.4 to -9.1
|
-11.1 units on a scale
Interval -12.2 to -9.9
|
SECONDARY outcome
Timeframe: EoT (week 12)Population: FAS.
ICGI was assessed by 7-point ordinate scale. Participants who were "Very much improved" or "Much improved" were defined as responders.
Outcome measures
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=188 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Percentage of Participants With an Investigator-rated Clinical Global Impression (ICGI) Response
|
53.2 percentage of participants
Interval 45.8 to 60.6
|
57.4 percentage of participants
Interval 50.0 to 64.6
|
SECONDARY outcome
Timeframe: EoT (week 12)Population: FAS.
PCGI was assessed by 7-point ordinate scale. Participants who were "Very much improved" or "Much improved" were defined as responders.
Outcome measures
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=188 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Percentage of Participants With a Patient-rated Clinical Global Impression (PCGI) Response
|
50.5 percentage of participants
Interval 43.1 to 57.9
|
56.4 percentage of participants
Interval 49.0 to 63.6
|
SECONDARY outcome
Timeframe: Baseline and EoT (week 12)Population: FAS
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.
Outcome measures
| Measure |
Placebo
n=185 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=187 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Change From Baseline in Pittsburgh Sleep Quality Index Total Score (PSQI)
|
-1.7 units on a scale
Interval -2.1 to -1.4
|
-1.7 units on a scale
Interval -2.1 to -1.4
|
SECONDARY outcome
Timeframe: Baseline and EoT (week 12)Population: FAS.
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.
Outcome measures
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=187 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Change From Baseline in Athens Insomnia Scale
|
-2.5 units on a scale
Interval -2.9 to -2.0
|
-2.5 units on a scale
Interval -2.9 to -2.0
|
SECONDARY outcome
Timeframe: Baseline and EoT (week 12)Population: FAS.
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.
Outcome measures
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=188 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Change From Baseline in Restless Legs Syndrome (RLS) Pain Score
|
-0.9 units on a scale
Interval -1.2 to -0.7
|
-1.0 units on a scale
Interval -1.2 to -0.7
|
SECONDARY outcome
Timeframe: Baseline and EoT (week 12)Population: FAS.
Health status was assessed by general visual analog scale (VAS). The VAS ranges from 0 (worst health status) and 100 (best health status).
Outcome measures
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=187 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Change From Baseline in Health Status Score of EuroQol-5 Dimension-5 Level (EQ-5D-5L)
|
2.7 units on a scale
Standard Deviation 16.7
|
4.2 units on a scale
Standard Deviation 15.3
|
SECONDARY outcome
Timeframe: From first dose of study drug up to week 13Population: Safety Analysis Set (SAF) consisted of all participants given at least one dose of the study drug for the treatment period.
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.
Outcome measures
| Measure |
Placebo
n=186 Participants
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=189 Participants
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events
Any TEAEs
|
71 Participants
|
94 Participants
|
|
Number of Participants With Adverse Events
Drug-related TEAEs
|
36 Participants
|
60 Participants
|
|
Number of Participants With Adverse Events
TEAEs leading to death
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Serious TEAEs
|
0 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Drug-related serious TEAEs
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
TEAEs leading to discontinuation of study drug
|
4 Participants
|
4 Participants
|
|
Number of Participants With Adverse Events
Drug-related TEAEs leading to disc. of study drug
|
3 Participants
|
4 Participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 32 other events
Deaths: 0 deaths
Gabapentin Enacarbil
Serious events: 3 serious events
Other events: 59 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=186 participants at risk
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=189 participants at risk
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/186 • From first dose of study drug up to week 13
|
0.53%
1/189 • Number of events 1 • From first dose of study drug up to week 13
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/186 • From first dose of study drug up to week 13
|
0.53%
1/189 • Number of events 1 • From first dose of study drug up to week 13
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/186 • From first dose of study drug up to week 13
|
0.53%
1/189 • Number of events 1 • From first dose of study drug up to week 13
|
Other adverse events
| Measure |
Placebo
n=186 participants at risk
Placebo was administered orally once daily after the evening meal.
|
Gabapentin Enacarbil
n=189 participants at risk
Gabapentin enacarbil was administered orally once daily after the evening meal. Participants with an estimated creatinine clearance of ≥ 60 mL/min to \< 90 mL/min at the start of the run-in period were administrated gabapentin enacarbil 300 mg for 1 week (upward titration period) followed by gabapentin enacarbil 600 mg for 11 weeks.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
10.8%
20/186 • Number of events 22 • From first dose of study drug up to week 13
|
12.7%
24/189 • Number of events 26 • From first dose of study drug up to week 13
|
|
Nervous system disorders
Somnolence neonatal
|
7.0%
13/186 • Number of events 13 • From first dose of study drug up to week 13
|
13.2%
25/189 • Number of events 26 • From first dose of study drug up to week 13
|
|
Nervous system disorders
Dizziness
|
0.00%
0/186 • From first dose of study drug up to week 13
|
10.6%
20/189 • Number of events 21 • From first dose of study drug up to week 13
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
- Publication restrictions are in place
Restriction type: OTHER