Clinical trial NCT03053427: A Study of Oral Dosing of Gabapentin Enacarbil in Japanese Restless Legs Syndrome Patients
Official title: Gabapentin Enacarbil Post-marketing Clinical Study A Randomized, Double-blind, Placebo-controlled, Parallel-group Study in Subjects With Restless Legs Syndrome.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Restless Legs Syndrome (RLS)
Keywords: Restless Legs Syndrome
ASP8825
Gabapentin enacarbil
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2017-02-15
Enrollment: 375
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in International Restless Legs Syndrome Rating Scale (IRLS) Score at Week 12
timeFrame: Baseline and week 12
Secondary outcomes:
measure: Change From Baseline in IRLS Score at Each Time Point
timeFrame: Baseline and weeks 1, 2, 4, 6, 8, 10, 12 and EoT (week 12)
measure: Percentage of Participants With an Investigator-rated Clinical Global Impression (ICGI) Response
timeFrame: EoT (week 12)
measure: Percentage of Participants With a Patient-rated Clinical Global Impression (PCGI) Response
timeFrame: EoT (week 12)
measure: Change From Baseline in Pittsburgh Sleep Quality Index Total Score (PSQI)
timeFrame: Baseline and EoT (week 12)
measure: Change From Baseline in Athens Insomnia Scale
timeFrame: Baseline and EoT (week 12)
measure: Change From Baseline in Restless Legs Syndrome (RLS) Pain Score
timeFrame: Baseline and EoT (week 12)
measure: Change From Baseline in Health Status Score of EuroQol-5 Dimension-5 Level (EQ-5D-5L)
timeFrame: Baseline and EoT (week 12)
measure: Number of Participants With Adverse Events
timeFrame: From first dose of study drug up to week 13
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Site JP00025
state: Aichi
city: Nagoya
country: Japan
facility: Site JP00029
state: Aichi
city: Nagoya
country: Japan
facility: Site JP00040
state: Aichi
city: Kitakyushu
country: Japan
facility: Site JP00006
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Site JP00022
state: Fukuoka
city: Sapporo
country: Japan
facility: Site JP00002
state: Hokkaido
city: Sapporo
country: Japan
facility: Site JP00003
state: Hokkaido
city: Sapporo
country: Japan
facility: Site JP00004
state: Hokkaido
city: Sapporo
country: Japan
facility: Site JP00023
state: Hokkaido
city: Kawanishi
country: Japan
facility: Site JP00041
state: Hyogo
city: Kobe
country: Japan
facility: Site JP00005
state: Hyogo
city: Kawasaki
country: Japan
facility: Site JP00038
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP00007
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP00017
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP00049
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP00050
state: Kanagawa
city: Yokosuka
country: Japan
facility: Site JP00009
state: Kanagawa
city: Sakai
country: Japan
facility: Site JP00032
state: Osaka
city: Tokorozawa
country: Japan
facility: Site JP00043
state: Saitama
city: Arakawa
country: Japan
facility: Site JP00012
state: Tokyo
city: Chofu
country: Japan
facility: Site JP00001
state: Tokyo
city: Chofu
country: Japan
facility: Site JP00028
state: Tokyo
city: Chuo
country: Japan
facility: Site JP00018
state: Tokyo
city: Chuo
country: Japan
facility: Site JP00024
state: Tokyo
city: Meguro
country: Japan
facility: Site JP00048
state: Tokyo
city: Musashino
country: Japan
facility: Site JP00034
state: Tokyo
city: Nakano
country: Japan
facility: Site JP00046
state: Tokyo
city: Ota
country: Japan
facility: Site JP00019
state: Tokyo
city: Shibuya
country: Japan
facility: Site JP00011
state: Tokyo
city: Shinagawa
country: Japan
facility: Site JP00013
state: Tokyo
city: Shinagawa
country: Japan
facility: Site JP00015
state: Tokyo
city: Shinagawa
country: Japan
facility: Site JP00016
state: Tokyo
city: Shinjuku
country: Japan
facility: Site JP00008
state: Tokyo
city: Shinjuku
country: Japan
facility: Site JP00014
state: Tokyo
city: Shinjuku
country: Japan
facility: Site JP00021
state: Tokyo
city: Chiba
country: Japan
facility: Site JP00031
city: Fukuoka
country: Japan
facility: Site JP00036
city: Kyoto
country: Japan
facility: Site JP00020
city: Kyoto
country: Japan
facility: Site JP00035
city: Osaka
country: Japan
facility: Site JP00010
city: Osaka
country: Japan
facility: Site JP00026
city: Osaka
country: Japan
facility: Site JP00037
city: Osaka
country: Japan
facility: Site JP00039
city: Osaka
country: Japan
facility: Site JP00047
city: Saitama
country: Japan
facility: Site JP00030
city: Saitama
country: Japan
facility: Site JP00044
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: