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NG2-73 reduces latency to persistent sleep in model of transient insomnia, Phase II data show

Wednesday, December 12 2007 | Comments

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What's This? NG2-73, an investigational gamma aminobutyric acid-a (GABAa) partial agonist, appears to significantly reduce latency to persistent sleep (LPS) in a model of transient insomnia, findings from a Phase II study conducted in healthy volunteers suggest.

The double-blind, multicenter study included 369 volunteers aged 24 to 63 years with no self-reported sleep disorders. Participants were randomized to receive a single dose of NG2-73 1 mg, 3 mg, 10 mg, or 20 mg, or placebo. The drug was administered approximately 2.5 hrs prior to each participant's median habitual bedtime; polysomnographic monitoring and "lights out" began 30 min postdose.

All doses of NG2-73 statistically significantly reduced LPS relative to placebo, with an apparent dose-response relationship. The mean LPS was 17.8 min in the group that received NG2-73 1 mg, 10.6 min in the 3 mg group, 7.8 min in the 10 mg group, and 6.6 min in the 20 mg group, while the mean LPS was 30.8 min in the placebo group.

In addition, the study authors noted that NG2-73 significantly increased total sleep time and sleep efficiency relative to placebo at doses >=3 mg. Moreover, there were significant differences between all NG2-73 doses and placebo in subjective ratings of "refreshing sleep."

According to the investigators, the drug was well tolerated; adverse events included sedation, somnolence, and dizziness. There were no drug-related adverse events, or serious adverse events, nor were there clinically significant changes in laboratory test results, vital signs, or electrocardiograms. (Scharf MB. Poster NR599.)

Separately, in a Phase I crossover study of NG2-73 that used exposure-response modeling to identify a potentially optimal dose of the drug, researchers found that a 4 mg to 5 mg oral dose of NG2-73 provided a maximal response that was similar to that observed with zolpidem 10 mg. In addition, next-day Digit Symbol Substitution Test scores suggested a plasma concentration of NG2-73 <2 ng/mL at 8 hrs to 9 hrs postdose should be targeted to minimize residual next-day effects.

In this study, plasma concentrations associated with half-maximal effects (assessed with subjective and observer ratings using a visual analog scale) were approximately 13 times greater with zolpidem than with NG2-73. At the same time, for a given dose (10 mg), maximum plasma concentration was 6-fold greater with zolpidem than with NG2-73.

"As the plasma half-life of NG2-73 is relatively short (<1.3 hrs), compound dosage forms with components having different release rates to produce sleep onset and maintain sleep throughout the night, while minimizing next-day residual cognitive effects, are being studied," the authors added. (Riggs MM, et al. Poster NR584.)

This information concerns a use that has not been approved by the Food and Drug Administration.

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