US group Merck & Co and Danish drugmaker Lundbeck A/S have reported promising data from a Phase II trial assessing their experimental sleep drug gaboxadol, adding further support to its potential as a novel treatment for both primary and transient insomnia.
Clinical evaluation of gaboxadol, a first-in-class selective extrasynaptic GABA(A) receptor agonist, revealed that it was able to induce statistically significant increases in deep sleep at all doses tested (5mg, 10mg, 15mg and 20mg).
The programme was split into two arms – one investigating the drug’s utility in treating primary insomnia, and one looking at transient insomnia, ie. temporary sleep problems occurring because of jet lag, for example.
The first evaluation was based on non-rapid eye movement data collected from two separate randomized, double-blind, cross-over polysomnograph studies, with the aim of comparing the dose response characteristics of gaboxadol to placebo after two nights of treatment.
Study one evaluated 40 patients given gaboxadol (10mg and 20 mg), zolipdem (10mg) or placebo in a four-way cross-over trial, and found that the agent increased slow wave activity by a rate of 33% and 54%, respectively (p<0.01), and boosted theta activity by a 24% and 34%, respectively (p<0.01 and p<0.001) compared to placebo.
Study two tested 26 patients treated with gaboxadol (5mg and 15mg) and placebo in a three-way cross-over trial. The 15mg dose increased slow wave activity by 21% (p<0.05) and theta activity by 20% (p<0.001) versus placebo, but no significant effect was seen at the 5mg dose.
The transient insomnia arm comprised a randomized, double-blind, five-way cross-over study of gaboxadol 5mg, 10mg and 15mg in 109 healthy subjects. In self-reported measures, subjects administered 10mg and 15mg experienced improvements in the time it took them to fall asleep, and at all doses there were significant benefits in the overall time spent asleep, the amount of time spent awake following sleep onset, and the amount of times woken up throughout the night.
On polysomnographic measures of sleep efficacy, gaboxadol 10mg and 15mg significantly reduced time to sleep by 31% and 33% (p<0.05 and p<0.01, respectively). No doses significantly affected the number of awakenings, but all three boosted total sleep time (5mg: 8%, 10mg: 10% and 15mg: 8%; all p<0.001) and decreased wakefulness after sleep onset (5mg: 25%, p<0.01; 10mg: 27%, p<0.01; and 15mg: 22%; p<0.05).
The agent’s safety profile also seems fairly robust, it having being well tolerated in the study with the majority of adverse events mild to moderate in nature, the researchers said. Importantly, no consistent next-day residual effects – often described as hangover-like ailments and associated with some of the insomnia drugs on the market - were recorded in the study.
Gaboxadol is currently in Phase III testing, and the groups hope to submit a filing to the US Food and Drug Administration in the first quarter of next year. If approved, the agent will compete against the likes of Takeda’s Rozerem (ramelteon), Sanofi-Aventis' Ambien (zolpidem) and Sepracor's Lunesta (eszopiclone).