Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS.
OBJECTIVE
To assess the efficacy and tolerability of the nondopaminergic agent XP13512/GSK1838262 in adults with moderate to severe primary restless legs syndrome (RLS).


METHODS
Patient Improvements in Vital Outcomes following Treatment in Restless Legs Syndrome I was a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of XP13512 1,200 mg or placebo taken once daily at 5:00 pm with food. Coprimary endpoints were mean change from baseline International Restless Legs Scale (IRLS) total score and proportion of investigator-rated responders (very much improved or much improved on the Clinical Global Impression-Improvement scale) at week 12 (last observation carried forward). Tolerability was assessed using adverse events, vital signs, and clinical laboratory parameters.


RESULTS
A total of 222 patients were randomized (XP13512 = 114, placebo = 108) and 192 patients (XP13512 = 100, placebo = 92) completed the study. At week 12, the mean change from baseline IRLS total score was greater with XP13512 (-13.2) compared with placebo (-8.8). Analysis of covariance, adjusted for baseline score and pooled site, demonstrated a mean treatment difference of -4.0 (95% confidence interval [CI], -6.2 to -1.9; p = 0.0003). More patients treated with XP13512 (76.1%) were responders compared with placebo (38.9%; adjusted OR 5.1; 95% CI, 2.8 to 9.2; p < 0.0001). Significant treatment effects for both coprimary measures were identified at week 1, the earliest time point measured. The most commonly reported adverse events were somnolence (XP13512 27%, placebo 7%) and dizziness (XP13512 20%, placebo 5%), which were mild to moderate in intensity and generally remitted.


CONCLUSIONS
XP13512 1,200 mg, taken once daily, significantly improved restless legs syndrome (RLS) symptoms compared with placebo and was generally well tolerated in adults with moderate to severe primary RLS.
Kushida
C A
CA
Stanford University Center of Excellence for Sleep Disorders, Stanford, CA 94305-5730, USA. clete@stanford.edu
Becker
P M
PM
Ellenbogen
A L
AL
Canafax
D M
DM
Barrett
R W
RW
D000328:Adult; D000588:Amines / Q000493:pharmacokinetics; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D003509:Cyclohexanecarboxylic Acids / Q000493:pharmacokinetics; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D023381:Endpoint Determination / Q000379:methods; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D010919:Placebos; D012148:Restless Legs Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy / Q000503:physiopathology; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C493250:1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; D000588:Amines; D014151:Anti-Anxiety Agents; D002219:Carbamates; D003509:Cyclohexanecarboxylic Acids; D018755:GABA Agonists; D010919:Placebos; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin