Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data

Rationale Sex-related differences in the clinical profiles of some insomnia medications have been previously reported. Objective To evaluate the clinical profile of suvorexant, a novel orexin receptor antagonist approved for treating insomnia at doses up to 20 mg, by sex subgroups. Methods Efficacy analyses by sex were based on pooled data from two similar phase 3, randomized, double-blind, placebo-controlled, 3-month trials in elderly (≥65 years) and non-elderly (18–64 years) insomnia patients. Two age-adjusted (non-elderly/elderly) dose regimes of 40/30 and 20/15 mg were evaluated, with fewer patients assigned to 20/15 mg. Efficacy was assessed by patient-reported outcomes ( N = 1264 women, 707 men) and by polysomnography endpoints in ~75% of patients. Safety analyses by sex ( N = 1744 women, 1065 men) included pooled data from the two 3-month trials plus 3-month data from a safety trial of 40/30 mg. Results The sex subgroup efficacy analyses mirrored the improvements seen for suvorexant 40/30 and 20/15 mg over placebo on patient-reported outcomes and polysomnography sleep maintenance and onset endpoints in the primary analyses; 95% CIs excluded zero in favor of suvorexant for most endpoints in both sexes, and similar efficacy was observed between sexes (95% CIs overlapped). Suvorexant was well-tolerated in women and men, although women in all treatment groups (including placebo) reported more adverse events than men. The most frequent adverse event was somnolence (women: 11.1% for 40/30 mg, 8.5% for 20/15 mg, 2.3% for placebo; men: 10.1% for 40/30 mg, 3.4% for 20/15 mg, 4.2% for placebo). Conclusion Suvorexant was generally effective and well-tolerated in both women and men with insomnia. ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629, NCT01021813.