Preclinical studies demonstrated that
ocinaplon, a positive allosteric modulator of
GABA(A) receptors, possesses
anxiolytic-like actions at doses devoid of the side effects typically associated with
benzodiazepines. The aim of this study was to evaluate the effects of
ocinaplon in a multicenter, double-blind proof-of-concept trial of male and female outpatients who met DSM-IV criteria for GAD with no coexisting depression, and had a baseline score of > or =20 on the Hamilton Scale for Anxiety (HAM-A). Patients with <20% reduction in HAM-A to placebo in a single-blind 7-day run-in period were randomly assigned to treatment with
ocinaplon 90 mg t.i.d. (n = 31) or placebo for 28 days (n = 29).
Ocinaplon was more effective than placebo in reducing HAM-A scores (P= 0.009). Patients assigned to
ocinaplon exhibited a mean improvement of 14.2 points (SE = 2.6) on the total score of the HAM-A scale at the conclusion of the trial, while patients assigned to placebo obtained a mean improvement of 6.3 points (SE = 2.0). A significant (P= 0.023) difference in improvement between
ocinaplon and placebo was observed beginning at and continuing from 1-week after the initiation of dosing. The proportion of patients with treatment-emergent adverse events (TEAE) was not statistically significant between
ocinaplon and placebo. One serious adverse event (SAE) occurred in the
ocinaplon group that was considered possibly related to study medication (
icterus following
transaminase elevations). The patient had preexisting medical conditions that may have contributed to this SAE. A full recovery was observed with no residual effects. The overall safety profile revealed no patterns of TEAEs, including those effects typically associated with other
anxiolytic and/or
benzodiazepine compounds, such as sedation.
Ocinaplon appears to be a well-tolerated and effective treatment for GAD. It produces a rapid onset of
anxiolytic action absent the side effects (e.g.,
dizziness, sedation) typically reported following
anxiolytic doses of
benzodiazepines.