ISTANBUL, TURKEY – The novel sleep aid eplivanserin proved to be well tolerated, with no effects on next-day cognitive or psychomotor performance, whether given alone or in combination with zolpidem in a randomized, double-blind, placebo- and benzodiazepine-controlled crossover trial.
Eplivanserin (Ciltyri) is an investigational agent, the furthest along in terms of development in a new drug class called the antagonists of serotonin two-A receptors, or ASTARs. Eplivanserin increases EEG slow-wave sleep, Dr. Christine Roycxplained at the annual congress of the European College of Neuropsychopharmacology.
As an ASTAR, eplivanserin would be expected to avoid impairment of next-day functioning, unlike benzodiazepines, which exert their hypnotic effect by binding to GABA receptors, added Dr. Roy of Sanofi Aventis in Chilly-Mazarin France.
She presented a study in which eplivanserin's effects upon cognitive and psychomotor performance were compared to those of flurazepam and placebo in 24 healthy subjects. In the first portion of the study, participants were randomized to a single bedtime 30-mg dose of flurazepam or placebo. The next morning they had to complete six psychometric tests. After a 21-day washout period, subjects were switched to the other treatment arm and testing was repeated.
The morning after taking flurazepam, participants displayed significantly worse cognitive performance, significantly more sedation, and–somewhat surprisingly–significantly better psychomotor performance than after placebo.
In the second phase of the study, subjects took 5 mg of eplivanserin or placebo at bedtime on 21 consecutive nights, then took the six psychometric tests on the morning of day 22. That night they took 10 mg of immediate-release zolpidem (Ambien) with their eplivanserin or placebo, then once again underwent psychometric testing the following morning. Then the eplivanserin and placebo groups were crossed over, and the sequence was repeated.
After 21 nights of eplivanserin, the test results for next-day cognitive and psychomotor performance and sedation weren't significantly different from the following 21 nights of placebo. The same was true after taking eplivanserin plus zolpidem, compared with placebo plus zolpidem, Dr. Roy reported.
In September, the Food and Drug Administration responded to Sanofi Aventis' application for marketing approval for eplivanserin in patients with sleep maintendata on the drug's risk/benefit ratio.
Dr. Roy's randomized trial was sponsored by Sanofi Aventis.