Assess the safety and tolerability of BHV-7000 across multiple ascending dose (MAD) studies.

BHV-7000 is a novel, small molecule, selective activator of Kv7.2/7.3 potassium channels in late-stage clinical development for epilepsy and neuropsychiatric disorders. In preclinical studies, BHV-7000 demonstrated minimal GABA_A receptor activation and exhibited potent anti-seizure efficacy without negative effects on neurobehavior or motor function. A Phase 1 EEG study confirmed CNS target engagement of BHV-7000.

Results were pooled from Phase 1 placebo-controlled MAD studies. Healthy adults aged 18-55 years were included, and participants were randomized to oral BHV-7000 immediate release (10, 25, 40, 80, or 120 mg daily), extended-release (25, 50, or 75 mg daily), or matching placebo, and treated for up to 15 days. Safety evaluations throughout the studies included AE monitoring, clinical laboratory tests, vital signs, ECGs, physical examinations, and suicidality assessments.

Across the MAD cohorts, 66 participants received BHV-7000 (N=53) or placebo (N=13). Adverse events (BHV-7000 vs placebo) occurring in ≥5% of participants included headache (11.3% vs 23.1%), back pain (11.3% vs 0%), constipation (5.7% vs 23.1%), and dizziness (5.7% vs 15.4%). There were low rates of CNS-related AEs; no somnolence was reported. The majority of AEs were mild and resolved spontaneously. There were no serious AEs, severe AEs, or dose-limiting toxicities. No AEs were reported amongst participants receiving BHV-7000 75 mg extended release (n=12), the highest dose in ongoing Phase 2/3 studies.

BHV-7000 was safe and well tolerated in multiple-dose Phase 1 studies across all doses evaluated for up to 15 days. Adverse events typically associated with other ASMs, such as somnolence and cognitive/mood disturbances, were not reported at equivalent doses to those currently being dosed in Phase 3 trials in focal epilepsy, generalized epilepsy, major depressive disorder, and bipolar disorder.