Clinical Profile of Suvorexant over 3 Months in Elderly Patients With Insomnia: Subgroup Analysis of Phase-3 Data (S53.006)

OBJECTIVE: To evaluate the clinical profile of suvorexant in elderly insomnia patients. BACKGROUND: Suvorexant is a first-in-class orexin-receptor-antagonist treatment for insomnia. Phase-3 trials evaluated age-adjusted (non-elderly/elderly) dose-regimes of 40/30mg and 20/15mg. DESIGN/METHODS: The pooled efficacy-analysis was pre-specified and included elderly data from two similar randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in elderly (蠅65y) and non-elderly (18-64y) insomnia patients. Fewer patients were assigned to 20/15mg than 40/30mg or placebo. Efficacy was assessed by patient-reported-outcomes (PRO), and by objective polysomnographic (PSG) endpoints in a subgroup of ~75[percnt] of patients. Safety was assessed by adverse events (AEs), with systematic assessment for special considerations including residual effects, abuse potential, suicidality, and cataplexy. The pooled safety-analysis included elderly data from the 3-month trials plus 3-month data from a 1-year safety trial of 40/30mg. RESULTS: The numbers of elderly patients in the efficacy-analysis of PRO endpoints were 30mg=313, 15mg=198, placebo=307. In elderly patients, suvorexant 30mg improved PRO and PSG measures of sleep-maintenance (subjective-total-sleep-time, wakefulness-after-persistent-sleep-onset ) and sleep-onset (subjective-time-to-sleep-onset, latency-to-persistent-sleep) compared to placebo at the earliest timepoints (Week-1 for PRO and Night-1 for PSG measures) and Month-3 (p<0.05). Results were similar for 15mg, except for the PRO and PSG onset measures at Month-3 (p=0.05 and p=0.09, respectively). The numbers of elderly patients in the safety-analysis were 30mg=627, 15mg=202, placebo=469. Suvorexant was generally well-tolerated in elderly patients with few discontinuations due to AEs (30mg=6.4[percnt], 15mg=3.5[percnt], placebo=5.5[percnt]). The most frequent AE was somnolence (30mg=8.8[percnt], 15mg=5.4[percnt], placebo=3.2[percnt]) which was generally transient and mild-to-moderate in intensity. CONCLUSIONS: Suvorexant 30mg and 15mg were effective and generally well-tolerated over 3-months in elderly insomnia patients. The FDA’s current emphasis is on using the lowest effective dose for insomnia treatments. Consequently, 10mg is the recommended dose in the US with a maximum dose of 20mg in both elderly and non-elderly patients. Study Supported by: Merck Disclosure: Dr. Herring has received personal compensation for activities with Merck & Co. Inc., as an employee. Dr. Connor has received personal compensation for activities with Merck & Co., Inc. as an employee. Dr. Ivgy-May has received personal compensation for activities with Merck & Co. Inc. as an employee. Dr. Snavely has received personal compensation for activities with Merck & Co., Inc. as an employee. Dr. Snyder has received personal compensation for activities with Merck & Co. Inc., as an employee. Dr. Michelson has received personal compensation for activities with Merck & Co., Inc. as an employee.