Gaboxadol, the first member of a new class of sleep agents, selective extrasynaptic GABA-A agonists, showed promise in a phase II trial for patients with primary insomnia and has entered phase III testing, according to a presentation at the 19th Annual Meeting of the Associated Professional Sleep Societies (USA).

Gaboxadol demonstrated significant improvement over placebo in several study endpoints for both sleep initiation and sleep maintenance in patients with primary insomnia. Gaboxadol 15 mg also significantly increased the amount of slow wave sleep patients experienced. Gaboxadol was generally well tolerated with no observed next-day residual effects.

“The findings of this early stage trial show that gaboxadol significantly improved several measures of sleep initiation and sleep maintenance in patients with Primary Insomnia,” said Stephen Deacon, PhD, lead investigator of the study and head of Clinical Development, Sleep Disorders, Lundbeck U.K. “Gaboxadol 15 mg significantly reduced Total Time Awake by 16 percent and Latency to Persistent Sleep by 21 percent, compared to placebo. The findings of this Phase II study demonstrate the therapeutic potential of gaboxadol as a treatment for insomnia. It will be important to confirm these findings in larger clinical trials.”

“The mechanism of action for gaboxadol appears to be unique relative to other sleep agents in that it selectively targets the extrasynaptic GABAA receptors,” said Tom Roth, Ph.D., director, Sleep Disorders & Research Center, Henry Ford Hospital, Detroit. “These receptors have a significant presence in areas of the brain thought to be important for sleep regulation.”

The randomized, double-blind, 3-way crossover, placebo-controlled polysomnograph (PSG) study evaluated 26 patients aged 18-65 years diagnosed with Primary Insomnia (DSM-IV criteria) to assess acute efficacy and safety of gaboxadol. Patients were administered gaboxadol 5 mg, 15 mg, or placebo 30 minutes before bedtime on two consecutive nights during three sessions separated by 7 to 14 days.

Baseline measures confirmed that patients had difficulty in falling and remaining asleep. Patients evaluated their subjective sleep quality using the Leeds Sleep Evaluation Questionnaire. Next-day residual effects were assessed using the Cognitive Drug Research (CDR) test battery.

The efficacy analyses were based on the average of nights one and two and were presented as group means. Compared with placebo, gaboxadol 5 mg and 15 mg significantly reduced Total Time Awake by 15 percent and 16 percent, respectively (5 mg: 58.2 minutes, 15 mg: 57.3 minutes, placebo: 68.5 minutes, p<0.05) and improved Total Sleep Time by 3 percent (5 mg: 419.8 minutes, p<0.05; 15 mg: 420.3 minutes, p<0.01; placebo: 408.7 minutes).

Additionally, compared with placebo, gaboxadol 15 mg significantly reduced Latency to Persistent Sleep by 21 percent (15 mg: 23.6 minutes, placebo: 30 minutes, p<0.05) and increased by 21 percent the amount of time patients spent in Slow Wave Sleep (15 mg: 114 minutes, placebo: 93.9 minutes, p<0.001).

In this small investigational study, no statistically significant treatment effect was observed on wakefulness during sleep or number of awakenings, although both doses reduced wakefulness during sleep on the first night of treatment.

Patients treated with gaboxadol showed no next-day residual effects based on the CDR test battery. Gaboxadol was generally well tolerated at both doses. Adverse events in the study were mild or moderate and included abdominal pain, somnolence, dizziness and headache.

Additional larger studies are underway to confirm these early findings and to further assess the efficacy and safety profiles of gaboxadol.