Pharmacokinetics and safety of ubrogepant when coadministered with calcitonin gene‒related peptide-targeted monoclonal antibody migraine preventives in participants with migraine: A randomized phase 1b drug–drug interaction study

Abhijeet Jakate, Andrew M. Blumenfeld, Ramesh Boinpally, Matthew Butler, Lisa Borbridge, Janette Contreras-De Lama, Danielle McGeeney, Antonia Periclou, Richard B. Lipton

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To evaluate the impact of two calcitonin gene–related peptide (CGRP)-targeted monoclonal antibodies (mAbs), erenumab and galcanezumab, on the pharmacokinetic (PK) profile, safety, and tolerability of ubrogepant. Background: People taking CGRP-targeted mAbs for migraine prevention sometimes take ubrogepant, an oral small-molecule CGRP receptor antagonist, for acute treatment of breakthrough migraine attacks. Design: In this two-arm, multicenter, open-label, phase 1b trial, adults with migraine were randomized to arm 1 (ubrogepant ± erenumab) or arm 2 (ubrogepant ± galcanezumab). The PK profile of ubrogepant was characterized for administration before and 4 days after CGRP-targeted mAb injection. Participants received single-dose ubrogepant 100 mg on day 1, subcutaneous erenumab 140 mg (arm 1) or galcanezumab 240 mg (arm 2) on day 8, and ubrogepant 100 mg once daily on days 12–15. In each study arm, serial blood samples were drawn on days 1 and 12 for measurement of plasma ubrogepant concentrations. The primary outcomes were area under the plasma ubrogepant concentration–time curve (AUC) from time 0 to t post-dose (AUC0–t) and from time 0 to infinity (AUC0–inf), and maximum plasma concentration (Cmax) of ubrogepant when ubrogepant was administered before or after a single dose of erenumab or galcanezumab. Vital signs and laboratory parameters were monitored. Results: Forty participants enrolled (20 per arm; mean [standard deviation] ages, 32.2 [8.9] and 38.4 [8.8] years; 50% [10/20] and 60% [12/20] female in arms 1 and 2, respectively). There were no significant differences in ubrogepant Cmax after versus before erenumab administration (geometric least-squares mean [LSM] ratio, 1.04 [90% CI, 0.93–1.16]), and no significant differences in AUC0–t (1.06 [0.96–1.16]) or AUC0–inf (1.05 [0.96–1.15]). Similarly, ubrogepant Cmax (1.00 [90% CI, 0.82–1.20]), AUC0–t (1.05 [0.90–1.23]), and AUC0–inf (1.05 [0.90–1.22]) geometric LSM ratios were statistically equivalent after galcanezumab versus ubrogepant alone. Treatment-emergent adverse events (TEAEs) were similar to those reported with each treatment alone. No serious TEAEs, TEAEs leading to discontinuation, or clinically relevant changes in laboratory parameters or vital signs were reported. Conclusions: The PK profile of ubrogepant was not significantly changed and no safety concerns were identified when ubrogepant was coadministered with erenumab or galcanezumab.

Original languageEnglish (US)
Pages (from-to)642-652
Number of pages11
JournalHeadache
Volume61
Issue number4
DOIs
StatePublished - Apr 2021

Keywords

  • CGRP
  • calcitonin gene‒related peptide
  • erenumab
  • galcanezumab
  • headache
  • ubrogepant

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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