Effects of Zavegepant and Concomitant Sumatriptan on Blood Pressure and Pharmacokinetics in Healthy Adult Participants (P9-12.005)

Abstract

<h3>Objective:</h3> 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. <h3>Background:</h3> Zavegepant (BHV-3500; formerly vazegepant) is a high-affinity, selective, small-molecule CGRP receptor antagonist in development for migraine. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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 &lt;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. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Richard Bertz has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Richard Bertz has stock in Biohaven Pharmaceuticals. The institution of Dr. Bhardwaj has received personal compensation in the range of $0-$499 for serving as a Consultant for Certara. Ms. Donohue has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc.. Ms. Donohue has received stock or an ownership interest from Biohaven Pharmaceuticals, Inc.. Jennifer Madonia has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Jennifer Madonia has stock in Biohaven Pharmaceuticals. Joseph Stringfellow has nothing to disclose. Matt Anderson has received personal compensation for serving as an employee of Certara. An immediate family member of Matt Anderson has received personal compensation for serving as an employee of Bristol Myers Squibb. Matt Anderson has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Certara Strategic Consulting. An immediate family member of Matt Anderson has received stock or an ownership interest from Bristol Myers Squibb. Beth Morris has received personal compensation for serving as an employee of Biohaven Pharmaceuticals Inc. Beth Morris has received stock or an ownership interest from Biohaven Pharmaceuticals Inc. Vlad Coric has received personal compensation for serving as an employee of Biohaven. Vlad Coric has received stock or an ownership interest from Biohaven. Vlad Coric has received intellectual property interests from a discovery or technology relating to health care. Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care.