A randomized phase 1 single-dose polysomnography study of ASP8062, a GABA_B receptor positive allosteric modulator

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Polysomnography and EEG endpoints can assess GABAergic activity.
• The effects of GABA_B receptor positive allosteric modulators on sleep are not well understood.

Purpose of the Study:

• To compare single doses of ASP8062 (35 mg or 70 mg) with placebo and paroxetine (40 mg) in healthy adults.
• To evaluate the impact of ASP8062 on sleep architecture, electroencephalography, and growth hormone release.

Main Methods:

• Healthy volunteers were randomized to four treatment groups: 35 mg ASP8062, 70 mg ASP8062, 40 mg paroxetine, or placebo.
• Polysomnography was used to measure primary endpoints: time in stage N3 (slow-wave sleep, SWS) and time in rapid eye movement (REM) sleep.
• Secondary endpoints included sleep stages, EEG parameters, pharmacokinetics, growth hormone (GH) levels, and safety.

Main Results:

• ASP8062 demonstrated a significant, dose-dependent increase in SWS, primarily in the first third of the night.
• ASP8062 did not affect REM sleep duration, while paroxetine reduced REM sleep.
• A dose-dependent trend of increased GH release was observed with ASP8062. Headache and nausea were the most common mild adverse events.

Conclusions:

• Single doses of ASP8062 showed evidence of central nervous system (CNS) penetration.
• ASP8062 enhanced GABAergic activity, indicated by increased SWS and GH release.
• The findings support further investigation of ASP8062 for potential therapeutic applications.