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

Primary Purpose

Restless Legs Syndrome (RLS)

Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Placebo
Gabapentin enacarbil
Sponsored by
Astellas Pharma Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Restless Legs Syndrome (RLS) focused on measuring Restless Legs Syndrome, ASP8825, Gabapentin enacarbil

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Site JP00025
  • Site JP00029
  • Site JP00040
  • Site JP00006
  • Site JP00022
  • Site JP00002
  • Site JP00003
  • Site JP00004
  • Site JP00023
  • Site JP00041
  • Site JP00005
  • Site JP00038
  • Site JP00007
  • Site JP00017
  • Site JP00049
  • Site JP00050
  • Site JP00009
  • Site JP00032
  • Site JP00043
  • Site JP00012
  • Site JP00001
  • Site JP00028
  • Site JP00018
  • Site JP00024
  • Site JP00048
  • Site JP00034
  • Site JP00046
  • Site JP00019
  • Site JP00011
  • Site JP00013
  • Site JP00015
  • Site JP00016
  • Site JP00008
  • Site JP00014
  • Site JP00021
  • Site JP00031
  • Site JP00036
  • Site JP00020
  • Site JP00035
  • Site JP00010
  • Site JP00026
  • Site JP00037
  • Site JP00039
  • Site JP00047
  • Site JP00030
  • Site JP00044

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Gabapentin enacarbil

Arm Description

Placebo was administered orally once daily after the evening meal.

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 followed by gabapentin enacarbil 600 mg for 11 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change From Baseline in IRLS Score at Each Time Point
ANCOVA model with the baseline value as a covariate was used.
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.
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.
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.
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.
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.
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).
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.

Full Information

First Posted
February 12, 2017
Last Updated
October 15, 2019
Sponsor
Astellas Pharma Inc
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1. Study Identification

Unique Protocol Identification Number
NCT03053427
Brief Title
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

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
March 30, 2017 (Actual)
Primary Completion Date
June 25, 2018 (Actual)
Study Completion Date
June 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Restless Legs Syndrome (RLS)
Keywords
Restless Legs Syndrome, ASP8825, Gabapentin enacarbil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
375 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was administered orally once daily after the evening meal.
Arm Title
Gabapentin enacarbil
Arm Type
Experimental
Arm Description
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 followed by gabapentin enacarbil 600 mg for 11 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral administration
Intervention Type
Drug
Intervention Name(s)
Gabapentin enacarbil
Other Intervention Name(s)
Regnite
Intervention Description
Oral administration
Primary Outcome Measure Information:
Title
Change From Baseline in International Restless Legs Syndrome Rating Scale (IRLS) Score at Week 12
Description
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.
Time Frame
Baseline and week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in IRLS Score at Each Time Point
Description
ANCOVA model with the baseline value as a covariate was used.
Time Frame
Baseline and weeks 1, 2, 4, 6, 8, 10, 12 and EoT (week 12)
Title
Percentage of Participants With an Investigator-rated Clinical Global Impression (ICGI) Response
Description
ICGI was assessed by 7-point ordinate scale. Participants who were "Very much improved" or "Much improved" were defined as responders.
Time Frame
EoT (week 12)
Title
Percentage of Participants With a Patient-rated Clinical Global Impression (PCGI) Response
Description
PCGI was assessed by 7-point ordinate scale. Participants who were "Very much improved" or "Much improved" were defined as responders.
Time Frame
EoT (week 12)
Title
Change From Baseline in Pittsburgh Sleep Quality Index Total Score (PSQI)
Description
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.
Time Frame
Baseline and EoT (week 12)
Title
Change From Baseline in Athens Insomnia Scale
Description
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.
Time Frame
Baseline and EoT (week 12)
Title
Change From Baseline in Restless Legs Syndrome (RLS) Pain Score
Description
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.
Time Frame
Baseline and EoT (week 12)
Title
Change From Baseline in Health Status Score of EuroQol-5 Dimension-5 Level (EQ-5D-5L)
Description
Health status was assessed by general visual analog scale (VAS). The VAS ranges from 0 (worst health status) and 100 (best health status).
Time Frame
Baseline and EoT (week 12)
Title
Number of Participants With Adverse Events
Description
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.
Time Frame
From first dose of study drug up to week 13

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Pharma Inc
Official's Role
Study Director
Facility Information:
Facility Name
Site JP00025
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Site JP00029
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Site JP00040
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Site JP00006
City
Kitakyushu
State/Province
Fukuoka
Country
Japan
Facility Name
Site JP00022
City
Kitakyushu
State/Province
Fukuoka
Country
Japan
Facility Name
Site JP00002
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Site JP00003
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Site JP00004
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Site JP00023
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Site JP00041
City
Kawanishi
State/Province
Hyogo
Country
Japan
Facility Name
Site JP00005
City
Kobe
State/Province
Hyogo
Country
Japan
Facility Name
Site JP00038
City
Kawasaki
State/Province
Kanagawa
Country
Japan
Facility Name
Site JP00007
City
Yokohama
State/Province
Kanagawa
Country
Japan
Facility Name
Site JP00017
City
Yokohama
State/Province
Kanagawa
Country
Japan
Facility Name
Site JP00049
City
Yokohama
State/Province
Kanagawa
Country
Japan
Facility Name
Site JP00050
City
Yokohama
State/Province
Kanagawa
Country
Japan
Facility Name
Site JP00009
City
Yokosuka
State/Province
Kanagawa
Country
Japan
Facility Name
Site JP00032
City
Sakai
State/Province
Osaka
Country
Japan
Facility Name
Site JP00043
City
Tokorozawa
State/Province
Saitama
Country
Japan
Facility Name
Site JP00012
City
Arakawa
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00001
City
Chofu
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00028
City
Chofu
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00018
City
Chuo
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00024
City
Chuo
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00048
City
Meguro
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00034
City
Musashino
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00046
City
Nakano
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00019
City
Ota
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00011
City
Shibuya
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00013
City
Shinagawa
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00015
City
Shinagawa
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00016
City
Shinagawa
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00008
City
Shinjuku
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00014
City
Shinjuku
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00021
City
Shinjuku
State/Province
Tokyo
Country
Japan
Facility Name
Site JP00031
City
Chiba
Country
Japan
Facility Name
Site JP00036
City
Fukuoka
Country
Japan
Facility Name
Site JP00020
City
Kyoto
Country
Japan
Facility Name
Site JP00035
City
Kyoto
Country
Japan
Facility Name
Site JP00010
City
Osaka
Country
Japan
Facility Name
Site JP00026
City
Osaka
Country
Japan
Facility Name
Site JP00037
City
Osaka
Country
Japan
Facility Name
Site JP00039
City
Osaka
Country
Japan
Facility Name
Site JP00047
City
Osaka
Country
Japan
Facility Name
Site JP00030
City
Saitama
Country
Japan
Facility Name
Site JP00044
City
Saitama
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."
Links:
URL
https://astellasclinicalstudyresults.com/hcp/study.aspx?ID=333
Description
Link to results on the Astellas Clinical Study Results website

Learn more about this trial

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

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