The Effect of Gabapentin Enacarbil on Pain Associated with Moderate-to-Severe Primary Restless Legs Syndrome in Adults: Pooled Analyses from Three Randomized Controlled Trials.

Abstract

BACKGROUND:

Adults with moderate-to-severe primary restless legs syndrome (RLS) often experience painful dysesthesias, which may lead to impaired quality of life.

OBJECTIVES:

The aim of this study was to assess the effects of gabapentin enacarbil (GEn) on pain associated with moderate-to-severe primary RLS in adults.

METHODS:

Data were pooled from three double-blind, randomized, placebo-controlled, 12-week trials (NCT00298623, NCT00365352, NCT01332305) for adults receiving GEn or placebo once daily. Change in average daily RLS pain score and a combined International Restless Legs Scale (IRLS)-pain response were examined.

RESULTS:

The modified intention-to-treat population included 671 adults (placebo, n = 244; GEn 600 mg, n = 161; GEn 1200 mg, n = 266). Both GEn doses significantly improved average daily RLS pain score at week 12 (p < 0.001 for GEn 600 mg vs. placebo and GEn 1200 mg vs. placebo). The combined IRLS-pain response subanalysis included 366 patients with a baseline IRLS total score ≥15 and pain score ≥4 (placebo, n = 133; GEn 600 mg, n = 86; GEn 1200 mg, n = 147). Most patients were both IRLS and pain responders (placebo, 40 %; GEn 600 mg, 70 %; GEn 1200 mg, 67 %). Spearman rank correlations between IRLS total and pain score (change from baseline to week 12) were moderate or strong. The most frequent treatment-emergent adverse events were somnolence (placebo, 5 %; GEn 600 mg, 20 %; GEn 1200 mg, 23 %) and dizziness (placebo, 4 %; GEn 600 mg, 13 %; GEn 1200 mg, 22 %).

CONCLUSIONS:

This post hoc pooled analysis suggests that GEn (600 and 1200 mg) once daily significantly improved pain associated with moderate-to-severe primary RLS in adults; however, the analysis was not powered to detect statistical differences between the two GEn doses. Numerically, more GEn-treated patients had a combined IRLS-pain response than placebo-treated patients.

• Authors: Neal Hermanowicz, Aaron Ellenbogen, Gordon Irving, Mark Buchfuhrer, Mark J Jaros, Gwendoline Shang, Richard Kim
• Journal: CNS drugs (CNS Drugs) Vol. 30 Issue 5 Pg. 443-54 (05 2016) ISSN: 1179-1934 [Electronic] New Zealand
• PMID: 27095237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
• Carbamates
• Dopamine Agonists
• gamma-Aminobutyric Acid

Topics

• Adult
• Aged
• Carbamates (therapeutic use)
• Dopamine Agonists (therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Pain (drug therapy, etiology)
• Quality of Life
• Randomized Controlled Trials as Topic
• Restless Legs Syndrome (complications)
• Treatment Outcome
• Young Adult
• gamma-Aminobutyric Acid (analogs & derivatives, therapeutic use)