Abstract Details

Title Novel, Selective Kv7.2/7.3 Potassium Channel Activator, BHV-7000, Demonstrates Dose-dependent Pharmacodynamic Effects on EEG Parameters in Healthy Adults

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P8 - Poster Session 8 (5:30 PM-6:30 PM)

Poster/Presentation
Number 1-011

Objective Assess the pharmacodynamic effects of BHV-7000 on electroencephalogram (EEG) spectral power in healthy adults.

Background 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.

Design/Methods 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.

Results 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.

Conclusions 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 or had stock in Biohaven Pharmaceuticals.
Bharat Awsare (Biohaven)	Bharat Awsare has received personal compensation for serving as an employee of Biohaven. Bharat Awsare has or had stock in Biohaven.
Heather Sevinsky (Biohaven)	Ms. Sevinsky has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Ms. Sevinsky has stock in Biohaven Pharmaceuticals.
Eric Ashbrenner	Eric Ashbrenner has received personal compensation for serving as an employee of Biohaven. Eric Ashbrenner has stock in Biohaven. An immediate family member of Eric Ashbrenner has stock in Biohaven.
Randall Killingsworth (Biohaven Pharmaceuticals)	Randall Killingsworth has received personal compensation for serving as an employee of Biohaven. Randall Killingsworth has stock in Biohaven.
Racheal Kendrick (Certara)	Racheal Kendrick has received personal compensation for serving as an employee of Certara. Racheal Kendrick has stock in Certara.
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)	The institution of Caroline Neuray has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clouds of Care. The institution of Caroline Neuray has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Saniona.
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)	Dr. Dworetzky has received personal compensation for serving as an employee of Biohaven. Dr. Dworetzky has or had stock in Biohaven.Dr. Dworetzky has received intellectual property interests from a discovery or technology relating to health care.
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.

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