Results of a Phase II clinical trial with Gaboxadol, an investigational agent in Phase III for the treatment of insomnia and the first Selective Extrasynaptic GABA-A Agonist ( SEGA ), a new class of sleep agents, showed a significant improvement over placebo in several 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 in this research trial.

Gaboxadol appears to interact directly with the extrasynaptic GABA receptor recognition site and mediates its effects via a GABA-A receptor population that is different from that modulated by benzodiazepine receptor agonists.

This 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 the 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 seven to 14 days.

Baseline PSG 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 are 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 less than 0.05 ) and improved Total Sleep Time by 3 percent ( 5 mg: 419.8 minutes, p less than 0.05; 15 mg: 420.3 minutes, p less than 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 less than 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 less than 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.

Source: 19th Annual Meeting of the Associated Professional Sleep Societies ( APSS ), 2005

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