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.
Keywords: Gabapentin enacarbil; mood; pain; restless legs syndrome.