By Jenny Powers
ISTANBUL, Turkey -- September 18, 2009 -- Treatment with eplivanserin, alone or in combination with zolpidem immediate release (IR), for symptoms of nocturnal awakening and difficulty returning to sleep had no negative side effects on next-day psychomotor or cognitive performance in healthy individuals, researchers reported here September 15 at the 22nd European College of Neuropsychopharmacology (ECNP) Congress.
Nocturnal awakening and subsequent difficulty resuming sleep are common symptoms of insomnia that correlate with a high degree of daytime cognitive impairment. Eplivanserin is a novel antagonist of serotonin type 2A receptors that influences nocturnal awakening, which is associated with reduced slow-wave asleep.
Christine Roy, MD, sanofi-aventis, Research and Development, Chilly-Mazarin, France, and colleagues theorised that eplivanserin should increase slow-wave sleep. Because eplivanserin has no affinity for gamma-aminobutyric acid receptors, it does not affect sleep onset. For patients with both sleep-onset and sleep-maintenance difficulties, eplivanserin may be taken with zolpidem, a benzodiazepine receptor agonist
The primary objective of this single-centre, double-blind, 2- part, randomised, placebo- and active-controlled, 4-way crossover study was to determine the effect of eplivanserin on next-day psychomotor and cognitive performance. The secondary objectives were clinical safety and next-day performance of eplivanserin plus zolpidem.
Twenty-four healthy participants (aged 19-24 years) received either 1 evening dose of flurazepam 30 mg (as positive control) or placebo during the first part of the study (part A), followed by a 21-day washout period, followed by administration of the reverse treatment. During part B of the study, participants were administered either an evening dose of eplivanserin 5 mg or placebo for 21 days, followed by zolpidem-IR (10 mg), followed by administration of the reverse treatment. Psychomotor and cognitive performance was assessed the next morning with Critical Flicker Fusion (CFF), Choice Reaction Time (CRT), Immediate and Delayed Recall of Supraspan Word Lists (IDR), Compensatory Tracking Task (CTT), and Bond-Lader Visual Analogue Scale of Alertness.
The subjects showed significant impairment in global psychomotor and cognitive performance compared with placebo (P = .0001) with flurazepam treatment. By contrast, no significant difference in performance was observed between eplivanserin and placebo on CRT, IDR, CTT tests, but eplivanserin treatment was associated with a decrease in CFF (-1.01 Hz; P = .0002). The same pattern was observed with combined eplivanserin plus zolpidem-IR treatment; psychomotor and cognitive performance was not significantly different than with placebo except with CFF, which similarly decreased (-1.07 Hz; P = .002).
The researchers concluded that eplivanserin, alone or coadministered with zolpidem-IR, did not negatively affect next-day overall psychomotor or cognitive performance. Eplivanserin administered for 21 days was well tolerated both alone and in combination with zolpidem-IR. Furthermore, clinical safety was demonstrated.
Funding for this study was provided by sanofi-aventis.
[Eplivanserin in Healthy Participants: Psychomotor and Cognitive Performance, Alone and in Combination With Zolpidem. Abstract P.1.i.0303]
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