Long-term Maintenance Treatment of Restless Legs Syndrome With Gabapentin Enacarbil: A Randomized Controlled Study

Abstract

for the XP060 Study GroupObjective: To assess maintenance of efficacy and tolerability of gabapentin enacarbil in patients with moderate to severe primary restless legs syndrome (RLS). Patients and MethOds:This study (conducted April 18, 2006, to November 14, 2007) comprised a 24-week, single-blind (SB) treatment phase (gabapentin enacarbil, 1200 mg) followed by a 12-week randomized, double-blind (DB) phase. Responders from the SB phase (patients with improvements on the International Restless Legs Scale [IRLS] and investigator-rated Clinical Global Impression-Improvement scale at week 24 and stable while taking a gabapentin enacarbil dose of 1200 mg for at least 1 month before randomization) were randomized to gabapentin enacarbil, 1200 mg, or placebo once daily at 5 pm with food. The primary end point was the proportion of patients experiencing relapse (worse scores on the IRLS and investigator-rated Clinical Global Impression of Change scale on 2 consecutive visits at least 1 week apart or withdrawal because of lack of efficacy) during the DB phase.Results: A total of 221 of 327 patients completed the SB phase, 194 (96 in the gabapentin enacarbil group and 98 in the placebo group) were randomized to DB treatment, and 168 (84 in the gabapentin enacarbil group and 84 in the placebo group) completed the DB phase. A significantly smaller proportion of patients treated with gabapentin enacarbil (9/96 [9%]) experienced relapse compared with the placebo-treated patients (22/97 [23%]) (odds ratio, 0.353; 95% confidence interval, 0.2-0.8; P=.02). Somnolence and dizziness were the most common adverse events. One death occurred (unintentional choking during the SB phase) and was judged as being unrelated to the study drug. No clinically relevant changes were observed in laboratory values, in vital signs, or on electrocardiograms.cOnclusiOn: Gabapentin enacarbil, 1200 mg, maintained improvements in RLS symptoms compared with placebo and showed long-term tolerability in adults with moderate to severe primary RLS for up to 9 months of treatment. the study was funded by XenoPort inc, santa clara, ca. Research funding for the design and conduct of this study and the collection, management, analysis, and interpretation of the data were sponsored by XenoPort. Preparation, review, and approval of the submitted manuscript were sponsored by GlaxosmithKline, Research triangle Park, nc. dr bogan is a shareholder and employee of sleepMed; he has received consultancy fees from cephalon, GlaxosmithKline, and jazz Pharmaceuticals; has received research funding from actelion Pharmaceuticals, addrenex Pharmaceuticals, apnicure, arena Pharmaceuticals, boehringer ingelheim, cephalon, GlaxosmithKline, evotec, eli lilly and company, johnson & johnson, Merck & co, neurogen, Pfizer, novartis Pharmaceuticals, Philips, ResMed, sanofi-aventis, schwarz Pharma, sensory Medical, sepracor, vanda Pharmaceuticals, ventus Medical, and XenoPort; and has participated in speakers' bureaus for sanofi-aventis, sepracor, cephalon, and jazz Pharmaceuticals. ...

Effect of Gabapentin Enacarbil on Individual Items of the International Restless Legs Study Group Rating Scale and Post-sleep Questionnaire in Adults with Moderate-to-Severe Primary Restless Legs Syndrome: Pooled Analysis of 3 Randomized Trials

“…These results are consistent with previous findings 27, [28][29][30][31] Overall, these findings suggest that sleep disorders in RLS can be improved by treating RLS itself; however, for some patients the somnolence associated with a medication such as GEn may also have a secondary beneficial effect in addressing sleep-related issues.…”

New concepts in the management of restless legs syndrome

“…125 day) improved IRLS score at 24 weeks by 15.5 and that relapse was less common in the active treatment arm compared with placebo (9% v 23%; P=0.02). 138 Pregabalin-At a dose of 150-450 mg/day, pregabalin is considered effective for the treatment of RLS/WED for one year on the basis of class I evidence from one randomised, double blind study that evaluated the efficacy of pregabalin and the incidence of augmentation over 52 weeks in 719 patients. Pregabalin significantly reduced the IRLS score compared with pramipexole at 52 weeks (−3.8 and −3.1, respectively; P<0.001).…”

Possible Sites of Therapeutic Action in Restless Legs Syndrome: Focus on Dopamine and α₂δ Ligands

“…Common side effects of ␣ 2 ␦ ligands in patients with RLS include malaise, somnolence, dizziness, headache, dry mouth, and fatigue [41,43,44,46,48,49] . Unlike dopamine agonists, symptom rebound has not been observed following withdrawal of pregabalin or gabapentin enacarbil [49,50] .…”