Dose-Response and Pharmacokinetics of Gabapentin Enacarbil (GEn [XP13512 / GSK1838262]) in Restless Legs Syndrome
Condition: Restless Legs Syndrome
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome
Intervention: GEn (XP13512/GSK1838262); Placebo
Intervention description: Double-Blind Treatment Phase: 600 mg GEn (XP13512) orally, once daily for 3 days followed by 600 or 1200 mg on days 4-6, followed by 600 or 1200 or 1800 mg on days 7-9, followed by 600 or 1200 or 1800 or 2400 mg on days 10-84. Double-Blind Taper Phase: 600 or 1200 or 1800 mg GEn (XP13512) orally, once daily on days 85-86, followed by 600 mg or 1200 mg on days 87-88, followed by 600 mg on days 89-91; Placebo orally once daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 217.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The objective of the study was to generate the data necessary to determine the gabapentin
      exposure produced by 4 dose levels of GEn (600 mg, 1200 mg, 1800 mg, and 2400 mg) or placebo,
      and the corresponding relief of symptoms in subjects with Restless Legs Syndrome (RLS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men or women at least 18 years of age

          -  RLS, based on the IRLSSG Diagnostic Criteria

          -  History of RLS symptoms occurring at least 15 nights in the month prior to Screening
             or, if on RLS treatment, this frequency of symptoms must have been applicable prior to
             start of treatment

          -  Documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights

          -  Total RLS severity score of 15 or greater on the IRLS Rating Scale

          -  If taking dopamine agonists, gabapentin, or other treatments for RLS (e.g., opioids,
             benzodiazepines) medications must have been discontinued at least 2 weeks prior to
             Screening;

          -  If taking any prescription medication, therapy must have been stabilized for at least
             3 months prior to Screening with no anticipated changes for the duration of the study;

          -  Body Mass Index (BMI) of 34 or below

          -  estimated creatinine clearance of at least 60 mL/min

        Exclusion Criteria:

          -  a sleep disorder (e.g., sleep apnea) that may significantly affect the assessment of
             RLS

          -  history of RLS symptom augmentation or end of dose rebound with previous dopamine
             agonist treatment

          -  neurologic disease or movement disorder (e.g., diabetic neuropathy, Parkinson's
             disease, multiple sclerosis, dyskinesias, and dystonias);

          -  other clinically significant or unstable medical condition or conditions which could
             affect RLS treatment efficacy assessments

          -  serum ferritin level below 20 ng/mL

          -  currently suffering from moderate or severe depression using the Diagnostic and
             Statistical Manual of Mental Disorders and Treatment IV (DSM IV TR)