Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS.

Abstract

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.

• Authors: C A Kushida, P M Becker, A L Ellenbogen, D M Canafax, R W Barrett, XP052 Study Group
• Journal: Neurology (Neurology) Vol. 72 Issue 5 Pg. 439-46 (Feb 03 2009) ISSN: 1526-632X [Electronic] United States
• PMID: 19188575 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
• Amines
• Anti-Anxiety Agents
• Carbamates
• Cyclohexanecarboxylic Acids
• GABA Agonists
• Placebos
• gamma-Aminobutyric Acid
• Gabapentin

Topics

• Adult
• Amines (pharmacokinetics)
• Anti-Anxiety Agents (pharmacokinetics)
• Carbamates (administration & dosage, adverse effects, pharmacokinetics)
• Central Nervous System (drug effects, physiology)
• Cyclohexanecarboxylic Acids (pharmacokinetics)
• Disorders of Excessive Somnolence (chemically induced)
• Dizziness (chemically induced)
• Double-Blind Method
• Drug Administration Schedule
• Endpoint Determination (methods)
• Female
• GABA Agonists (administration & dosage, adverse effects, pharmacokinetics)
• Gabapentin
• Humans
• Male
• Middle Aged
• Outcome Assessment, Health Care (methods)
• Placebos
• Restless Legs Syndrome (drug therapy, physiopathology)
• Sleep Initiation and Maintenance Disorders (drug therapy, physiopathology)
• Treatment Outcome
• gamma-Aminobutyric Acid (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)