BALTIMORE—Suvorexant may reduce time to sleep onset and improve sleep maintenance for patients with insomnia, according to study results presented at the 27th Annual Meeting of the Associated Professional Sleep Societies. The magnitude of the drug’s effect may increase with dose, but suvorexant appears to provide consistent benefits to elderly and nonelderly subjects, said Neely Ivgy-May, PhD. The drug’s enhancement of sleep maintenance persists throughout the night.
After three months of treatment with suvorexant, mean time to sleep onset was reduced by approximately 30 minutes for patients receiving a high dose and by approximately 25 minutes for subjects taking a low dose, said Dr. Ivgy-May, Director of Clinical Research at Merck and Company in Whitehouse Station, New Jersey. Differences between drug and placebo were significant for both doses at each time point.
Two Trials Compared Suvorexant With Placebo
Dr. Ivgy-May’s presentation was based on a predefined analysis of pooled efficacy data from two phase III trials of suvorexant. The trials’ designs were similar; both lasted for three months, compared two doses of suvorexant with placebo, and included elderly and nonelderly subjects. Eligible patients had a diagnosis of primary insomnia, an average total sleep time of less than 6.5 hours, and a mean time to sleep onset of at least 30 minutes.
In total, 2,041 patients were randomized: 775 participants received high-dose suvorexant, 494 received low-dose suvorexant, and 772 received placebo. Nonelderly patients in the high-dose group received 40 mg of the drug nightly, and elderly patients received 30 mg nightly. In the low-dose group, nonelderly patients received 20 mg nightly, and elderly patients received 15 mg nightly. The doses in each group were matched for pharmacokinetic exposure.
All participants reported subjective time to sleep onset, total sleep time, and wake after sleep onset in a sleep diary. At night 1, month 1, and month 3, approximately 75% of the population underwent polysomnography (PSG), during which latency to persistent sleep and wake after persistent sleep onset (WASO) were measured.
Improved Latency to Persistent Sleep and Total Sleep Time
Latency to persistent sleep, as measured by PSG, was reduced by approximately 35 minutes after three months of high-dose suvorexant in one of the trials. Differences in time to sleep onset between low-dose suvorexant and placebo were significant at night 1 and month 1, but not at month 3. The diminished difference between the low dose and placebo at month 3 “is mostly due to an increase in placebo response in one of the two trials, rather than a real decline in efficacy,” said Dr. Ivgy-May.
Effective for Primary Insomnia
At baseline, patients reported a mean subjective total sleep time of approximately 5.25 hours. After three months of treatment, patients gained approximately an hour of sleep with high-dose suvorexant and 55 minutes of sleep with low-dose suvorexant. Subjects had 16 more minutes of sleep with the low dose than with placebo, and 22 more minutes of sleep with the high dose than with placebo, said Dr. Ivgy-May. At each time point, the differences between drug and placebo were statistically significant. In addition, WASO, as measured by PSG, was reduced by approximately 50 minutes for both doses.
—Erik Greb
Senior Associate Editor