Clinical trial NCT01332318: Simulated Driving Study in Restless Legs Syndrome
Official title: A Randomized, Double Blind, Active- and Placebo-Controlled, Parallel Group Safety Study Assessing Simulated Driving Performance in XP13512-(GSK1838262) Treated Patients With Restless Legs Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Restless Legs Syndrome
Lead sponsor: XenoPort, Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-11
Enrollment: 130
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was a multi center, randomized, double blind, active and placebo controlled, parallel group study to assess simulated driving performance in XP13512 treated subjects with Restless Legs Syndrome (RLS). Eligible subjects were randomized to receive a once daily dose of placebo (2 groups), XP13512 1200 mg, or XP13512 1800 mg for 16 days. On Day 16, one of the placebo groups also received one 50 mg dose of diphenhydramine (DPH) to assess the effects of an agent known to have sedative properties, while the other 3 groups received a DPH placebo.

Detailed description: This study was a multicenter, randomized, double blind, active and placebo controlled, parallel group study. Eligible subjects were randomized in a 1:1:1:1 ratio to 1 of the following 4 treatment groups:

A) XP13512 Placebo + Diphenhydramine Placebo (Pbo) B) XP13512 1200 mg/day + Diphenhydramine Placebo (1200 mg) C) XP13512 1800 mg/day + Diphenhydramine Placebo (1800 mg) D) XP13512 Placebo + 50 mg Diphenhydramine (Pbo/DPH)

Eligibility criteria: Inclusion Criteria:

* Men or women who were 21 through 65 years of age and fluent in English;
* Subjects with RLS, based on the IRLSSG Diagnostic Criteria;
* Currently a licensed and experienced driver who has driven an average of 3 or more times/week for the past 3 years;
* Able to successfully complete the 5 minute practice simulated driving test at Screening;
* History of RLS symptoms at least 15 nights in the prior month or, if on treatment, this frequency of symptoms before treatment was started;
* Total RLS severity score of 15 or greater on the IRLS Rating Scale;
* Documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights Discontinuation of treatments for RLS (e.g., opioids, benzodiazepines, dopamine agonists and/or gabapentin) at least 2 weeks prior to Screening; -
* Body Mass Index of 34 or below;
* Estimated creatinine clearance of at least 60 mL/min;
* Agreed to maintain abstinence from alcohol and smoking throughout the entire study period;
* Agreed to maintain abstinence from caffeine from midnight of the day prior to and until the end of each Visit (Visits 2 to 4).

Exclusion Criteria:

* A sleep disorder (e.g., sleep apnea) other than RLS that may significantly affect the assessment of RLS;
* Current use of a sleeping medication or sedating medication;
* Current use of CNS stimulants;
* Neurologic disease or movement disorder;
* Other medical conditions which could affect RLS assessments;
* Significant medical history that may impair psychomotor coordination;
* Subjects who had clinically significant or unstable medical conditions;
* Serum ferritin level below 20 ng/mL;
* Subjects currently suffering from moderate or severe depression using the Diagnostic and Statistical Manual of Mental Disorders and Treatment IV (DSM IV TR);
* Subjects with a history of substance abuse (alcohol or drugs) or substance dependence within 12 months prior to enrollment;
* Shift workers or subjects who were not on normal day/night sleep cycles;
* Subjects who had smoked an average of greater than one half pack of cigarettes (or nicotine equivalent) per day within 30 days of the Screening Visit;
* Subjects who had consumed an average of \>5 cups (i.e., 40 ounces) of caffeinated beverages per day within 20 days of the Screening Visit;
* Subjects with a history of allergy to gabapentin, diphenhydramine, or XP13512 excipients

Primary outcomes:
measure: Change From Baseline (Day -1) in Overall Lane Position Variability (LPV) on Day 16 (Tmax)
timeFrame: Baseline (Day -1) and Day 16
Secondary outcomes:
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Lane Position Variability (LPV)
timeFrame: Baseline (Days -1 and 1) and Days 14 and 15
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Lane Position
timeFrame: Baseline (Days -1 and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Speed Variability
timeFrame: Baseline (Day -1) and Days 14 and 16; baseline (Day 1) and Day 15
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Overall Average Speed
timeFrame: Baseline (Days -1 and 1) and Days 14, 15, and 16
measure: Number of Participants With the Indicated Number of Simulated Crashes on Days 14 (Evening), 15 (Morning After Dose), and 16 (Tmax)
timeFrame: Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in Brake Reaction Time
timeFrame: Baseline (Days -1 and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Alertness Visual Analog Scale (VAS) Score
timeFrame: Baseline (Days -1 and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) in the Epworth Sleepiness Scale (ESS) Total Score
timeFrame: Baseline (Day -1) and Day 14
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Composite Score
timeFrame: Baseline (Days -1 and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Memory Test Score
timeFrame: Baseline (Days -1and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Digit Sequencing Score (DSS)
timeFrame: Baseline (Days -1and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Token Motor Task Test Score
timeFrame: Baseline (Days -1and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Verbal Fluency Test Score
timeFrame: Baseline (Days -1 and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Symbol Coding Test Score
timeFrame: Baseline (Days -1and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Brief Assessment of Cognition (BAC) Scaled Tower of London (TOL) Score
timeFrame: Baseline (Days -1and 1) and Days 14, 15, and 16
measure: Mean Change From Baseline (Day -1) at Day 14 in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score
timeFrame: Baseline (Day -1) and Day 14
measure: Number of Participants in Each Category of the Investigator-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14
timeFrame: Day 14
measure: Number of Participants Who Responded to Treatment Based on Scores on the Investigator-Rated CGI-I at Day 14
timeFrame: Day 14
measure: Number of Participants in Each Category of the Participant-Rated Clinician Global Impression of Improvement (CGI-I) Scale at Day 14
timeFrame: Day 14
measure: Number of Participants Who Responded to Treatment Based on Scores on the Participant-Rated CGI-I at Day 14
timeFrame: Day 14
measure: Median Time to Onset of a Participant's First RLS Symptoms Using the 24-hour RLS Symptom Record at Day 14
timeFrame: Day 14
measure: Percentage of Participants With no Reported RLS Symptoms During the 24-hour RLS Record at Day 14
timeFrame: Day 14
measure: Number of Participants With no Reported RLS Symptoms During Each of the 4-hour Periods From the 24-hour RLS Record at Day 14
timeFrame: Day 14
measure: Number of Participants With the Indicated Post Sleep Questionnaire (PSQ) Responses at Day 14
timeFrame: Day 14
measure: Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) on the Pittsburgh Sleep Diary (PghSD) Sleep Onset Items
timeFrame: Baseline (Days -1and 1) and Days 14, 15, and 16
measure: Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Total Sleep Time Item
timeFrame: Baseline (Days -1 and 1) and Days 14, 15, and 16
measure: Mean Change From Baseline (Day -1) to Day 14 (Evening) and Day 16 (at Tmax) and Change From Baseline (Day 1) to Day 15 (Morning After Dose) in the Pittsburgh Sleep Diary (PghSD) Sleep Quality
timeFrame: Baseline (Day -1and 1) and Days 14, 15, and 16
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: