RESUMO
OBJECTIVE: Two doses of EVT 201, a partial positive allosteric modulator of the GABA(A) system, were evaluated in elderly primary insomnia patients with daytime sleepiness. PATIENTS AND METHODS: Participants were 149 elderly patients with DSM-IV primary insomnia including evidence of daytime sleepiness (53 males, 96 females; mean age 71.3yrs, range 65-86yrs). A randomized, multicentre, double-blind, placebo-controlled, parallel-group design was used to assess the hypnotic efficacy of EVT 201 1.5 and 2.5mg during seven consecutive nights. Polysomnography (PSG) was performed on nights 1, 6 and 7 of treatment. Daytime assessments on Day 8 included the multiple sleep latency test (MSLT), Rey Auditory Verbal Learning Test (RAVLT), Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale (KSS). The primary endpoint was total sleep time (TST) and the key secondary endpoint was mean MSLT latency. RESULTS: Compared to placebo, EVT 201 1.5 and 2.5mg increased TST (30.9, 56.4min, respectively; p=0.0001, p<0.0001); reduced wake after sleep onset (WASO; -15.2, -36.1min, respectively; p=0.014, p<0.0001); reduced latency to persistent sleep (LPS; -15.9, -19.9min, respectively; p=0.009, p=0.001). The 2.5mg dose also reduced WASO in hours 5-8 (-16.3min, p=0.001). Both doses also improved subjective sleep quality and usual subjective efficacy measures. A significantly longer mean MSLT latency was observed on Day 8 with both doses, compared to placebo (2min increase; p=0.03, both doses). The PVT, RAVLT, and POMS did not differ among treatment groups. No serious or unexpected treatment emergent adverse events were noted. CONCLUSION: EVT 201 improved PSG measures of sleep onset and sleep maintenance and significantly reduced daytime physiological sleep tendency. These findings suggest that treatment of primary insomnia in older patients has the potential to improve daytime sleepiness as well as sleep.
