Abstract Details

Title Effects of Zavegepant and Concomitant Sumatriptan on Blood Pressure and Pharmacokinetics in Healthy Adult Participants

Topic Headache

Presentation(s) P9 - Poster Session 9 (5:30 PM-6:30 PM)

Poster/Presentation
Number 2-005

Objective

Evaluate co-administration of zavegepant+sumatriptan on resting blood pressure (BP); pharmacokinetics (PK) of sumatriptan and zavegepant alone and combined; zavegepant effects on resting BP vs placebo; safety and tolerability of zavegepant+sumatriptan in healthy participants.

Background Zavegepant (BHV-3500; formerly vazegepant) is a high-affinity, selective, small-molecule CGRP receptor antagonist in development for migraine.

Design/Methods In a Phase 1, single-center, randomized, partially blind, placebo-controlled, one-arm study, participants received 2 sumatriptan 6mg subcutaneous (SC) injections ~1 hour apart (12mg; Days [D] 1,4) and zavegepant 10mg nasal spray or placebo (20mg; 1 per each nostril; D2-4), immediately after the second sumatriptan dose on D4. BP was recorded manually predose, then via ambulatory monitoring for 13 hours. Blood samples for pharmacokinetics (PK) were collected predose and postdose D1,3,4. Individual time-weighted average (TWA) of mean arterial pressure (MAP) was calculated. Treatment effects on BP and PK were compared via random effects repeated measures ANOVA.

Results Forty-two participants were dosed (36 zavegepant; 6 placebo) and 41 completed the study. The overall median (range) age was 31.0 (20 to 49) years. The difference in TWA of MAP between zavegepant+sumatriptan and sumatriptan was 0.04 mmHg; the upper bound of the comparison 90% confidence interval (CI) (-0.69, 0.77) was <5 mmHg, indicating similar MAP. The comparison ratios (90% CI) for sumatriptan with and without zavegepant were C_max: 104.13% (98.03%, 110.61%); AUC_0-inf: 102.46% (100.73%, 104.21%). The comparison ratios (90% CI) for zavegepant with and without sumatriptan were C_max:112.43% (103.36%, 122.29%); AUC_0-24: 96.74% (88.93%, 105.23%). Overall, 38 (90.5%) participants experienced ≥1 treatment-emergent adverse event (AE), with no deaths, serious AEs, or treatment-emergent AEs leading to dose discontinuation.

Conclusions Co-administration of zavegepant+sumatriptan resulted in no significant changes in BP compared to sumatriptan alone and no clinically meaningful change in the PK of sumatriptan or zavegepant. Overall, all treatments were well tolerated and exhibited a favorable safety profile.

Authors/Disclosures
Jing Liu PRESENTER	Jing Liu has received personal compensation for serving as an employee of Pfizer, Inc.. Jing Liu has stock in Pfizer, Inc. .
Richard Bertz (Biohaven Pharmaceuticals)	Richard Bertz has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Richard Bertz has stock in Biohaven Pharmaceuticals.
Rajinder Bhardwaj (Certara)	The institution of Rajinder Bhardwaj has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Biohaven .
Mary Donohue (Biohaven Pharmaceuticals, Inc.)	Mary Donohue has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc.. Mary Donohue has stock in Biohaven Pharmaceuticals, Inc..
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Vladimir Coric	Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care.
Robert Croop, MD	Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has received personal compensation for serving as an employee of Pfizer Inc.. Dr. Croop has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Collima LLC. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has stock in Biohaven Ltd.. Dr. Croop has stock in Actio Biosciences, Inc. . Dr. Croop has received research support from Pfizer Inc. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.

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