Gabapentin enacarbil in Japanese patients with restless legs syndrome: a 12-week, randomized, double-blind, placebo-controlled, parallel-group study

Abstract

Objective

Gabapentin enacarbil (GEn) was effective and well-tolerated for the treatment of restless legs syndrome (RLS) in North American studies. However, no placebo-controlled studies of GEn have been performed in Asian patients with RLS. Therefore, we investigated the efficacy and safety of GEn in Japanese patients with RLS to determine the optimal dosage.

Research design and methods

Outpatients with RLS (International Restless Legs Syndrome Rating Scale (IRLS) scores ≥15) were randomized (n = 474) and treated (n = 469) in a double-blind manner with once-daily placebo (n = 116), 600 (n = 120), 900 (n = 119) or 1200 (n = 114) mg GEn for 12 weeks.

Clinical trial registration

ClinicalTrials.gov identifier: NCT00530530.

Main outcome measure

The primary outcome was the change in IRLS score. Secondary outcomes included Investigator (ICGI)- and Patient (PCGI)-rated Clinical Global Impression and adverse events.

Results

The mean change in IRLS score from baseline to the final observation was −8.96 for placebo versus −11.10, −10.28 and −11.38 for 600, 900 and 1200 mg GEn. Williams’ multiple comparison test showed that only 1200 mg GEn was superior to placebo (p = 0.011). However, in post hoc mixed-effects models with repeated measures, which accounted for the time-course of changes in IRLS, the placebo-adjusted changes were −2.31, −1.92 and −2.31 for 600, 900 and 1200 mg GEn. ICGI and PCGI response rates were significantly greater for all three GEn doses versus placebo (all p ≤ 0.014). Adverse events, including somnolence, dizziness and nasopharyngitis, were frequent but of mild-to-moderate severity. However, there was a tendency toward a dose-dependent increase in the incidence of adverse events.

Conclusions

GEn is effective and well-tolerated for the treatment of RLS in Japanese patients. All three doses produced improvements in IRLS compared with placebo; 600 mg GEn is a suitable target dose. However, our analysis possibly introduced positive bias by assuming that symptoms improve after discontinuation.

Key words::

• Gabapentin enacarbil
• International Restless Legs Syndrome Rating Scale
• Japan
• Restless Legs Syndrome
• Tolerability

Transparency

Declaration of funding

This study was funded by Astellas Pharma Inc. Astellas Pharma Inc designed the study, funded its conduct during data collection, and funded editorial support for the preparation of the present paper.

Declaration of financial/other relationships

Y.I., K.H., N.U., K.K., N.H. and M.T. have all received financial support from Astellas Pharma Inc.

Y.I., K.H., N.U., K.K., N.H. and M.T. contributed to the study concept/design; Y.I., N.U. and K.K. conducted the study; Y.I. and M.T. performed data analysis and interpretation; and all authors contributed to the writing of the report.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors wish to acknowledge the editorial support of Nicholas Smith, PhD, in the preparation of this manuscript.