Simulated Driving Study in Restless Legs Syndrome

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

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.

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)

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