Phase 1, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Erenumab (AMG 334) and Concomitant Sumatriptan on Blood Pressure in Healthy Subjects (P2.161)

Objective: Assess the effects of subcutaneous (SC) sumatriptan alone and concomitant SC sumatriptan and intravenous (IV) erenumab on resting blood pressure (BP) in healthy subjects. Background: Erenumab is an anti-CGRP receptor monoclonal antibody in development for migraine prophylaxis. BP elevation is a known side effect of SC sumatriptan, a commonly used acute migraine medication. Increased BP is a theoretical possibility with CGRP inhibition. Design/Methods: In this one-way, parallel design study, 34 healthy adults were randomized to: Group A (sumatriptan alone, n=12) and Group B (concomitant sumatriptan and erenumab, n=22). Both groups received IV placebo on Day 1 and SC sumatriptan 12mg (Imitrex ™ ) on Day 2 (Part 1). After a 2-day washout, Group A received IV placebo and Group B received IV erenumab 140mg on Day 4, both groups received SC sumatriptan 12mg on Day 5 (Part 2). BP was assessed at 11 time points (Parts 1 and 2). The primary endpoint was time-weighted, resting mean arterial pressure, (MAP) calculated 2.5hrs post-dose on Day 2 and Day 5. For post-hoc analyses, changes in MAP were calculated 2hrs after each dose of investigational product. Results: Mean baseline BP was similar between groups. Overall, baseline mean (SD) systolic BP (SBP), diastolic BP (DBP), and MAP, respectively were 122.8 (6.5), 70.1 (5.6), and 87.5 (5.0) mmHg. No differences in SBP, DBP, or MAP were observed between subjects who received sumatriptan alone and those who received concomitant sumatriptan and erenumab (upper limit of the 90% CI for the treatment difference was Conclusions: Concomitant administration of IV erenumab 140mg with SC sumatriptan had no effect on resting BP compared with SC sumatriptan alone. Study Supported by: Amgen Inc. Disclosure: Dr. De Hoon has received personal compensation for activities with Ablynx, Merck Sharp & Dohme, Galderma, UCB, and Eli Lilly as an advisor and/or consultant. Dr. De Hoon has received research support from Amgen Inc., Abide, Galderma, Genentech, GSK, J&J, Merck Sharp & Dohme, and UCB. Dr. Hecken has nothing to disclose. Dr. Vandermeulen9s institution has received grants from GSK, Sanofi Pasteur, and AdImmune. Dr. Herbots has nothing to disclose. Dr. Kubo has received personal compensation for activities with Amgen Inc as an employee. Dr. Kubo holds stock and/or stock options in Amgen Inc., which sponsored research in which Dr. Kubo was involved as an investigator. Dr. Lee has received personal compensation for activities with Amgen, Inc. as an employee. Dr. Lee holds stock and/or stock options in Amgen, Inc., which sponsored research in which Dr. Lee was involved as an investigator. Dr. Eisele has received personal compensation for activities with Amgen Inc. as an employee. Dr. Eisele holds stock and/or stock options in Amgen Inc. Dr. Vargas has received personal compensation for activities with Amgen as an employee. Dr. Vargas holds stock in Amgen. Employee of Amgen Inc,,,,,,