Treatment response to sleep, pain, and mood disturbance and their correlation with sleep disturbance in adult patients with moderate-to-severe primary restless legs syndrome: Pooled analyses from 3 trials of gabapentin enacarbil

Abstract

Introduction. This pooled analysis investigated the effects of gabapentin enacarbil (GEn) on clinical correlates of sleep disturbance in adults with moderate-to-severe primary restless legs syndrome (RLS) and no-to-moderate or severe-to-very severe baseline sleep disturbance.

Methods. Co-primary end-points were mean change from baseline to week 12 in International Restless Legs Scale (IRLS) total score and proportion of responders (‘much’/‘very much’ improved) on the investigator-rated Clinical Global Impression–Improvement (CGI-I) scale (week 12). Pain, mood, individual IRLS items, and safety were assessed.

Results. The modified intent-to-treat population was 671 adults randomized to GEn 600 mg (n = 161), GEn 1200 mg (n = 266), or placebo (n = 244). GEn significantly improved least squares mean change in IRLS total score from baseline versus placebo for no-to-moderate (GEn 600 mg,− 12.3; 1200 mg, − 11.3; placebo, − 7.7) and severe-to-very severe (− 16.6; − 17.0; − 12.7) groups (all P < 0.01). Significantly more GEn-treated patients (both doses) were CGI-I responders (week 12) versus placebo in both sleep subgroups (all P < 0.01). GEn substantially improved mood and pain scores for both sleep subgroups versus placebo. The most frequent treatment-emergent adverse events were somnolence and dizziness.

Conclusion. GEn (600 mg and 1200 mg) was effective and well tolerated in adults with moderate-to-severe primary RLS regardless of baseline sleep disturbance level.

Key words::

• Gabapentin enacarbil
• mood
• pain
• restless legs syndrome

Declaration of interest: R.K.B. reports the following disclosures: shareholder, Chief Medical Officer, and employee of SleepMed Inc.; Board of Directors of SleepMed Inc., First Community Corporation, SC and National Sleep Foundation; consultant to Aerial, Jazz, ApniCure, UCB, Teva; Speakers Bureau for Teva, Jazz, UCB, and XenoPort, Inc.; industry-funded research for GSK, Jazz, Vanda, Merck, Novo Nordisk, Pfizer, XenoPort, Eisai, Philips, ResMed, Apnicure, Sensory Medical, J&J, Apnex, and Fisher Paykel. D.O.L. is a consultant to GSK, Lundbeck, and XenoPort, Inc. M.J.B. is consultant and speaker for XenoPort, Inc. and UCB Pharma, and conducts research for Xenon. M.J.J. is a paid consultant of XenoPort, Inc. R.K. and G.S. are employees of and own stock in XenoPort, Inc. These studies and this analysis were conducted by XenoPort, Inc., Santa Clara, CA, USA. Medical writing support was provided by Sachi Yim from CodonMedical, an Ashfield Company, and was funded by XenoPort, Inc.