Efficacy of the selective extrasynaptic GABA A agonist, gaboxadol, in a model of transient insomnia: a randomized, controlled clinical trial

Abstract

Objective: The hypnotic efficacy of gaboxadol, a selective extrasynaptic GABA A agonist (SEGA), was evaluated in a phase-advance model of transient insomnia.

Methods: Healthy subjects (18-64 years) completed a randomized, double-blind, parallel group study in which the sleep period was advanced 4h from habitual sleep time. Polysomnographic (PSG) and self-reported sleep measures were used to compare gaboxadol 10mg (N =271) and 15 mg (N =274) versus placebo (N =277).

Results: In the placebo group, the phase-advance procedure disrupted sleep maintenance as measured by PSG wakefulness after sleep onset (WASO) and self-reported WASO (sWASO), and also, to a lesser extent, disrupted sleep onset as measured by PSG latency to persistent sleep (LPS) and self-reported time to sleep onset (sTSO). Both doses of gaboxadol decreased WASO and sWASO versus placebo (p <or= 0.05). Gaboxadol 15 mg also reduced LPS versus placebo (p <or= 0.01) and both doses reduced sTSO versus placebo (p <or= 0.01). PSG and self-reported total sleep time as well as ratings of sleep quality were improved with both gaboxadol doses relative to placebo (all p <or= 0.01 or better). The amount of slow wave sleep (SWS) was greater with both doses of gaboxadol than with placebo (p <or= 0.001). No group differences in the amount of rapid eye movement sleep were found. Most PSG and self-report measures indicated a mild dose response. The percentage of subjects with adverse events was low (<10% in any treatment group) and all were mild or moderate; none were serious and gaboxadol did not impact morning gait or coordination.

Conclusions: Gaboxadol 10 and 15 mg were efficacious in significantly reducing the sleep maintenance and sleep onset disruption produced by this model of transient insomnia, with effects generally being most pronounced for the 15 mg dose. Gaboxadol also enhanced SWS.

Trial registration: ClinicalTrials.gov NCT00102167.