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Abstract Details

Novel, Selective Kv7.2/7.3 Potassium Channel Activator, BHV-7000, Demonstrates Dose-dependent Pharmacodynamic Effects on EEG Parameters in Healthy Adults
Epilepsy/Clinical Neurophysiology (EEG)
P8 - Poster Session 8 (5:30 PM-6:30 PM)
1-011
BHV-7000 is a novel, small molecule, selective activator of Kv7.2/7.3 potassium channels, a clinically validated target in epilepsy. In a first-in-human Phase 1 study, BHV-7000 was safe and well tolerated.
Assess the pharmacodynamic effects of BHV-7000 on electroencephalogram (EEG) spectral power in healthy adults.
This phase 1 open label study enrolled 11 healthy adult males/females aged 18-55 years. All subjects underwent sequential EEG recordings with the international 10-20 electrode setup at Day -1, Day 1, Day 5 and Day 9. Subjects received single doses of 10, 25, and 50 mg BHV-7000 (standard release formulation) on Days 1, 5 and 9 in a randomized sequence. EEG measurements included a 5-minute period of resting state with eyes open and 5 minutes of resting state with eyes closed at baseline, pre-dose, 1h, 2h, 3h, 4h and 6h post-dose. Quantitative spectral analysis of all EEG recordings was performed to assess pharmacodynamic effects over time. Cluster-based permutation analysis was conducted to identify statistically significant differences. BHV-7000 plasma levels were quantified at corresponding time points with EEG to assess concentration-response relationships.

Dose-dependent effects of BHV-7000 were observed in EEG spectral power in all frequency bands. The greatest increases in spectral power were seen in alpha, beta, and gamma bands. Changes were seen across all EEG channels, indicating a global central nervous system drug effect. Positive correlations were found between spectral power and BHV-7000 plasma concentration at the time of maximal response in all frequency bands.
Pharmacodynamic activity of BHV-7000 in the brain was demonstrated by dose- and concentration-dependent increases in EEG spectral power across all canonical frequency bands. The changes in faster frequencies and less so in the slower frequencies (delta and theta) is consistent with the absence of somnolence seen in the first-in-human BHV-7000 Phase 1 study. 







Authors/Disclosures
Jason Lerner, MD (Biohaven)
PRESENTER
Dr. Lerner has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Dr. Lerner has stock in Biohaven Pharmaceuticals.
Bharat Awsare (Biohaven) No disclosure on file
Heather Sevinsky (Biohaven) No disclosure on file
Eric Ashbrenner No disclosure on file
Randall Killingsworth (Biohaven Pharmaceuticals) No disclosure on file
Racheal Kendrick (Certara) No disclosure on file
Emiel Vereycken (Epilog, Clouds of Care NV) No disclosure on file
Nigel Colenbier (Epilog, Clouds of Care NV) No disclosure on file
Caroline Neuray (Epilog, Clouds of Care NV) No disclosure on file
Pieter Van Mierlo (Epilog, Clouds of Care NV) No disclosure on file
Jeremy D. Slater, MD, FAAN (Stratus) Dr. Slater has received personal compensation for serving as an employee of Stratus. Dr. Slater has stock in Zeto LLC.
DAVID WYATT (Syneos Health) No disclosure on file
Irfan Qureshi, MD (Biohaven Pharmaceuticals) Dr. Qureshi has received personal compensation for serving as an employee of Biohaven. Dr. Qureshi has stock in Biohaven Pharmaceuticals.
Steven Dworetzky (Biohaven) No disclosure on file
Michael E. Bozik, MD (Biohaven Pharmaceuticals) Dr. Bozik has received personal compensation for serving as an employee of Biohaven . Dr. Bozik has stock in Biohaven.