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

Restless Legs Syndrome (RLS) Clinical Trial

Official title:

Gabapentin Enacarbil Post-marketing Clinical Study A Randomized, Double-blind, Placebo-controlled, Parallel-group Study in Subjects With Restless Legs Syndrome.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03053427
• Other study ID #: 8825-CL-0101
• Status: Completed
• Phase: Phase 4
• Start date: March 30, 2017
• Est. completion date: June 25, 2018

Study information

• Verified date: October 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

After 1 week run in period with single-blind placebo, participants meeting the inclusion and none of the exclusion criteria were randomized to receive double-blind treatment with either gabapentin enacarbil 600 mg or placebo for 12 weeks treatment period. After then, single-blind placebo was given for 1 week for follow-up observation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 375
• Est. completion date: June 25, 2018
• Est. primary completion date: June 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subject has Restless Legs Syndrome (RLS), based on the International Restless Legs Syndrome Study Group (IRLSSG) Diagnostic Criteria.

• Subject has reported history of RLS symptoms for at least 15 days in the month prior to the first dosing; if on treatment, this frequency of symptoms was started before treatment.

• Subject with International Restless Legs Syndrome Rating Scale (IRLS) score = 15.

• Subject has discontinued dopamine agonists, and/or gabapentin at least 1 week prior to the first dosing.

• Subject has discontinued other treatments for RLS at least 2 weeks prior to the first dosing.

• Female subject must either:

Be of non-childbearing potential:

• Post-menopausal (defined as at least 1 year without any menses) prior to Screening, or

• documented surgically sterile

Or, if of childbearing potential:

• Agree not to try to become pregnant during the study and for 28 days after the final study drug administration

• And have a negative urine pregnancy test at Screening

• And, if heterosexually active, agree to consistently use two forms of highly effective birth control starting at Screening and throughout the study period and for 28 days after the final study drug administration.

• Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 28 days after the final study drug administration.

• Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.

• Subject agrees not to participate in another interventional study while on treatment.

• Subject with a Body Mass Index of = 18.5 and < 30.

• Subject with estimated creatinine clearance of = 60 mL/min.

Exclusion Criteria:

• Subject has a sleep disorder that may significantly affect the assessment of RLS.

• Subject has a history of RLS symptom augmentation or end-of-dose rebound with previous dopamine agonist treatment.

• Subject has neurologic disease or movement disorder.

• Subject has poorly controlled diabetes, iron deficiency anemia, or are currently taking any sedative/hypnotic.

• Subject has a history of suicide attempt within 6 months prior to informed consent.

• Subject has a high level of Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST).

• Subject is currently suffering from moderate or severe depression.

• Subject has a history of alcohol dependence or drug abuse, or subject had alcohol or drug abuse or dependence in the last 1 year.

• Subject is a shift worker, professional driver, or operator of dangerous machinery.

• Subject has clinically significant or unstable medical conditions.

• Subject has a history of hypersensitivity reaction to gabapentin.

• Subject has previously taken pregabalin, gabapentin enacarbil, or the study drug of Gabapentin enacarbil.

• Subject has participated in a clinical study for another investigational drug or medical device or post-marketing clinical study within 12 weeks (84 days) prior to the first dosing, or is currently participating in any of these studies.

Related Conditions & MeSH terms

• Psychomotor Agitation
• Restless Legs Syndrome
• Restless Legs Syndrome (RLS)
• Syndrome

Intervention

Drug:
• Placebo
Oral administration
• Gabapentin enacarbil
Oral administration

Locations

Country	Name	City	State
Japan	Site JP00012	Arakawa	Tokyo
Japan	Site JP00031	Chiba
Japan	Site JP00001	Chofu	Tokyo
Japan	Site JP00028	Chofu	Tokyo
Japan	Site JP00018	Chuo	Tokyo
Japan	Site JP00024	Chuo	Tokyo
Japan	Site JP00036	Fukuoka
Japan	Site JP00041	Kawanishi	Hyogo
Japan	Site JP00038	Kawasaki	Kanagawa
Japan	Site JP00006	Kitakyushu	Fukuoka
Japan	Site JP00022	Kitakyushu	Fukuoka
Japan	Site JP00005	Kobe	Hyogo
Japan	Site JP00020	Kyoto
Japan	Site JP00035	Kyoto
Japan	Site JP00048	Meguro	Tokyo
Japan	Site JP00034	Musashino	Tokyo
Japan	Site JP00025	Nagoya	Aichi
Japan	Site JP00029	Nagoya	Aichi
Japan	Site JP00040	Nagoya	Aichi
Japan	Site JP00046	Nakano	Tokyo
Japan	Site JP00010	Osaka
Japan	Site JP00026	Osaka
Japan	Site JP00037	Osaka
Japan	Site JP00039	Osaka
Japan	Site JP00047	Osaka
Japan	Site JP00019	Ota	Tokyo
Japan	Site JP00030	Saitama
Japan	Site JP00044	Saitama
Japan	Site JP00032	Sakai	Osaka
Japan	Site JP00002	Sapporo	Hokkaido
Japan	Site JP00003	Sapporo	Hokkaido
Japan	Site JP00004	Sapporo	Hokkaido
Japan	Site JP00023	Sapporo	Hokkaido
Japan	Site JP00011	Shibuya	Tokyo
Japan	Site JP00013	Shinagawa	Tokyo
Japan	Site JP00015	Shinagawa	Tokyo
Japan	Site JP00016	Shinagawa	Tokyo
Japan	Site JP00008	Shinjuku	Tokyo
Japan	Site JP00014	Shinjuku	Tokyo
Japan	Site JP00021	Shinjuku	Tokyo
Japan	Site JP00043	Tokorozawa	Saitama
Japan	Site JP00007	Yokohama	Kanagawa
Japan	Site JP00017	Yokohama	Kanagawa
Japan	Site JP00049	Yokohama	Kanagawa
Japan	Site JP00050	Yokohama	Kanagawa
Japan	Site JP00009	Yokosuka	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in International Restless Legs Syndrome Rating Scale (IRLS) Score at 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.	Baseline and week 12
Secondary	Change From Baseline in IRLS Score at Each Time Point	ANCOVA model with the baseline value as a covariate was used.	Baseline and weeks 1, 2, 4, 6, 8, 10, 12 and EoT (week 12)
Secondary	Percentage of Participants With an Investigator-rated Clinical Global Impression (ICGI) Response	ICGI was assessed by 7-point ordinate scale. Participants who were "Very much improved" or "Much improved" were defined as responders.	EoT (week 12)
Secondary	Percentage of Participants With a Patient-rated Clinical Global Impression (PCGI) Response	PCGI was assessed by 7-point ordinate scale. Participants who were "Very much improved" or "Much improved" were defined as responders.	EoT (week 12)
Secondary	Change From Baseline in Pittsburgh Sleep Quality Index Total Score (PSQI)	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.	Baseline and EoT (week 12)
Secondary	Change From Baseline in Athens Insomnia Scale	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.	Baseline and EoT (week 12)
Secondary	Change From Baseline in Restless Legs Syndrome (RLS) Pain Score	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.	Baseline and EoT (week 12)
Secondary	Change From Baseline in Health Status Score of EuroQol-5 Dimension-5 Level (EQ-5D-5L)	Health status was assessed by general visual analog scale (VAS). The VAS ranges from 0 (worst health status) and 100 (best health status).	Baseline and EoT (week 12)
Secondary	Number of Participants With Adverse Events	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.	From first dose of study drug up to week 13

External Links

•   Link to results on the Astellas Clinical Study Results website