WASHINGTON — Three-month administration of 15-mg and 30-mg doses of suvorexant, an orexin-receptor antagonist, was effective and well tolerated in a cohort of elderly patients with insomnia, according to study results presented at the 2015 American Academy of Neurology Annual Meeting.
In the pooled efficacy analysis, William Herring, MD, PhD, of Merck Research Laboratories, and fellow researchers culled together elderly (age, ≥65 years) insomnia patients from two similar randomized, double blind, placebo-controlled, parallel-group, three-month trials.
The final analysis included 313 elderly patients who received the 30-mg dose of suvorexant, 198 who received the 15-mg dose, and 307 who were given placebo.
Herring and colleagues assessed efficacy by patient reported outcomes (PRO) and by objective polysomnographic (PSG) endpoints in a subgroup of approximately 75% of patients, and used adverse events to determine safety. PRO and PSG measures of sleep maintenance were defined as subjective total sleep time and wakefulness after persistent sleep onset, whereas sleep onset was defined as subjective time to sleep onset and latency to persistent sleep.
Compared with placebo, 30 mg of suvorexant improved PRO and PSG measures of sleep maintenance and sleep onset at the earliest time points, including the first week for PRO and the first night for PSG measures, and at three months (P<.05). Comparable results were reported with the 15-mg dose, with the exception of three-month PRO (P=.05) and PSG onset measures (P=.09).
According to the safety analysis, which included 627 elderly patients in the 30-mg arm, 202 in the 15-mg arm, and 469 in the placebo arm, suvorexant was well tolerated. Furthermore, there were few discontinuations resulting from adverse events: 6.4% in the 30-mg arm; 3.5% in the 15-mg arm; and 5.5% in the placebo arm.
Of the adverse events, the most frequent was somnolence — 30 mg, 8.8%; 15 mg, 5.4%; placebo, 3.2% — though this was considered transient and of mild-to-moderate intensity.
In an interview with Neurology Advisor, Herring said that with the approval of suvorexant, the final dosing is for the lowest-effective dose of the drug.
“The U.S. label starts at 10 mg and may titrate up to 15 or 20 mg, and this is the dosing recommendation for both elderly and non-elderly patients,” he said.
Herring added that the mechanism of action — antagonism of orexin receptors — is relatively new to neuroscience, with its discovery in the late 1990s.
“So [suvorexant] represents a completely different mechanism of action from the other agents that are out there for sleep, and we believe offers an important alternative for the treatment of insomnia for our patients,” he said.
- Herring W et al. Abstract S53.006. Presented at: American Academy of Neurology Annual Meeting 2015; April 18-25, 2015; Washington, D.C.