A pilot open label, single dose trial of fenobam in adults with fragile X syndrome

TLDR

The study aimed to evaluate the safety and pharmacokinetics of a single oral dose of fenobam, an mGluR5 antagonist, in adults with fragile X syndrome. Twelve participants received a single 50–150 mg oral dose of fenobam, with pharmacokinetic sampling, vital signs, and side‑effect monitoring over 6 h, and pre‑ and post‑dose assessments of prepulse inhibition and continuous performance testing to probe sensory gating, attention, and inhibition. Fenobam was well tolerated with no clinically significant adverse effects, produced dose‑dependent but variable plasma concentrations peaking at 39.7 ng/ml after 150 mg, improved prepulse inhibition in half of the participants, but did not enhance continuous performance, and these results support further investigation of the drug in adults with fragile X syndrome.

Abstract

<h3>Objective:</h3> A pilot open label, single dose trial of fenobam, an mGluR5 antagonist, was conducted to provide an initial evaluation of safety and pharmacokinetics in adult males and females with fragile X syndrome (FXS). <h3>Methods:</h3> Twelve subjects, recruited from two fragile X clinics, received a single oral dose of 50–150 mg of fenobam. Blood for pharmacokinetic testing, vital signs and side effect screening was obtained at baseline and numerous time points for 6 h after dosing. Outcome measures included prepulse inhibition (PPI) and a continuous performance test (CPT) obtained before and after dosing to explore the effects of fenobam on core phenotypic measures of sensory gating, attention and inhibition. <h3>Results:</h3> There were no significant adverse reactions to fenobam administration. Pharmacokinetic analysis showed that fenobam concentrations were dose dependent but variable, with mean (SEM) peak values of 39.7 (18.4) ng/ml at 180 min after the 150 mg dose. PPI met a response criterion of an improvement of at least 20% over baseline in 6 of 12 individuals (4/6 males and 2/6 females). The CPT did not display improvement with treatment due to ceiling effects. <h3>Conclusions:</h3> Clinically significant adverse effects were not identified in this study of single dose fenobam across the range of dosages utilised. The positive effects seen in animal models of FXS treated with fenobam or other mGluR5 antagonists, the apparent lack of clinically significant adverse effects, and the potential beneficial clinical effects seen in this pilot trial support further study of the compound in adults with FXS.