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

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.

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.