Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling
This 5-week, open-label, single-blind, placebo-controlled study assessed the safety, pharmacokinetics, and efficacy of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1) in 30 adolescents (aged 12-17) with attention-deficit hyperactivity disorder (ADHD), specifically those carrying mutations in mGluR network genes. Mutation status was double-blinded. Participants underwent single-dose pharmacokinetic profiling with doses ranging from 50-800 mg, followed by a single-blind placebo period during week 1, and then symptom-driven dose escalation up to 400 mg twice daily (BID) for the remaining 4 weeks.
Fasoracetam treatment resulted in significant symptom improvement. The mean Clinical Global Impressions-Improvement (CGI-I) score improved from 3.79 at baseline to 2.33 at week 5 (P < 0.001), and the mean Clinical Global Impressions-Severity (CGI-S) score decreased from 4.83 at baseline to 3.86 at week 5 (P < 0.001). Parental Vanderbilt scores showed significant improvement in subjects with mGluR Tier 1 variants (P < 0.035). There were no significant differences in the incidence of adverse events between the placebo week and the weeks on active drug.