A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Study to Assess the Pharmacokinetics, Efficacy, and Safety of Gabapentin Enacarbil in Subjects With Restless Legs Syndrome

Abstract

Gabapentin exposure was approximately proportional to GEn dose. Efficacy data showed that a once-daily dose of GEn 600 to 2400 mg provides greater relief of RLS symptoms than placebo; GEn was generally well tolerated with an adverse event profile consistent with gabapentin.

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

“…The most commonly reported TEAEs with both GEn doses were somnolence and dizziness, as previously found in the primary analyses. [18][19][20] These TEAEs are consistent with the overall safety profile of GEn. 17 Our results expand on results from the individual studies and a previous pooled analysis of XP052, XP053, and XP081 by looking at individual scores from the IRLS and PSQ. In the previous analyses, GEn (600, 1200, 1800, and 2400 mg) significantly improved the co-primary end points from the pivotal trials as follows: change from baseline in IRLS total score and the proportion of responders on the investigator-rated Clinical Global Impression-Improvement scale compared with placebo.…”

“…[18][19][20] To summarize, each study was a 12-week, placebo-controlled, double-blind, randomized trial that enrolled adults with moderate-to-severe primary RLS, as defined by the IRLS Study Group diagnostic criteria. 1 Eligible patients were adults (Z18 years) who experienced RLS symptoms with a duration of at least 15 days during the month before screening (or, if on treatment, similar symptom frequency before the start of treatment), IRLS total score of at least 15, and documented RLS symptoms for at least 4 of 7 consecutive evenings/days during the baseline period.…”

“…[18][19][20] Data for the IRLS were collected at day 1 (baseline) and at weeks 1, 2, 3, 4, 6, 8, 10, and 12; data for the PSQ were collected at day 1 (baseline) and at weeks 4, 8, and 12. The follow-up time periods were also similar for each study (weeks 14-17 for XP052 and XP053, and week 17 for XP081).…”

“…17 Data from 3 randomized, double-blind, placebo-controlled studies (XP052, XP053, and XP081) found that adults with moderate-to-severe primary RLS experienced marked improvements in primary RLS symptoms after treatment with GEn compared with placebo. [18][19][20] In a previous pooled analysis of XP052, XP053, and XP081, GEn 600 and 1200 mg significantly improved the primary end points of IRLS total score and investigator-rated Clinical Global Impression-Improvement compared with placebo. 21 The most frequently reported treatment-emergent adverse events (TEAEs) in these studies were somnolence and dizziness.…”

Current Treatment of Selected Pediatric Sleep Disorders

“…Gabapentin's longer-acting analogue gabapentin enacarbil has recently been released on the market and has been studied in adults [121]. Clonidine, an antiadrenergic antihypertensive sometimes reported to be used for sleep onset difficulties in children, benzodiazepines, and opiates have all been reported or suggested for use in pediatric RLS, all with scant data [99].…”