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Objective: To evaluate potential drug-drug interactions of ubrogepant and atogepant.Background: Ubrogepant and atogepant, calcitonin gene-related peptide (CGRP) receptor antagonists, are recently approved drugs for acute and preventive treatment of migraine, respectively. For patients with migraine who are prescribed atogepant for the preventive treatment of migraine, health care providers could prescribe ubrogepant for the acute treatment of breakthrough migraine attacks.Methods: A phase Ib, multi-center, open-label, fixed-sequence study was conducted in participants diagnosed with migraine for at least 1 year. To assess the primary objective of pharmacokinetic interactions in this phase I trial, the highest United States Food and Drug Administration-approved individual dose strengths of atogepant (60 mg once daily) and ubrogepant (100 mg) were utilized, with ubrogepant being administered on a fixed-dose schedule every 3 days, regardless of whether a participant was experiencing a migraine attack. Secondary endpoints included safety and tolerability. Clinical safety measurements were monitored throughout the study. Results:Of the 31 participants enrolled, 26 completed the study. A single dose of ubrogepant had no statistically significant effect on atogepant pharmacokinetics. Coadministration of ubrogepant with atogepant resulted in a 19% increase (geometric mean ratio 118.80, 90% confidence interval [CI] 108.69-129.84) in the ubrogepant area under the plasma concentration-time curve and a 26% increase (geometric mean ratio 125.63, 90% CI 105.58-149.48) in the ubrogepant maximum plasma concentration. These statistically significant changes in ubrogepant exposure were not clinically meaningful, and no new safety concerns were identified for the combination.

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ABBV‐47D11 is a neutralizing monoclonal antibody that targets a mutationally conserved hydrophobic pocket distal to the ACE2 binding site of SARS‐CoV‐2. This first‐in‐human safety, pharmacokinetics, and antiviral pharmacodynamic assessment in patients with COVID‐19 provide an initial evaluation of this antibody that may allow further development. This multicenter, randomized, double‐blind, and placebo‐controlled single ascending dose study of ABBV‐47D11 (180, 600, or 2400 mg) as an intravenous infusion, was in hospitalized and non‐hospitalized (confined) adults with mild to moderate COVID‐19. Primary outcomes were grade 3 or higher study drug‐related adverse events and infusion‐related reactions. Secondary outcomes were pharmacokinetic parameters and concentration‐time profiles to Day 29, immunogenicity (anti‐drug antibodies), and antiviral activity (change in RT‐PCR viral load) from baseline to Days 15 and 29. ABBV‐47D11 single doses up to 2400 mg were safe and tolerated and no safety signals were identified. The pharmacokinetics of ABBV‐47D11 were linear and showed dose‐proportional increases in serum concentrations with ascending doses. The exploratory anti‐SARS‐CoV‐2 activity revealed a reduction of viral load at and above the 600 mg dose of ABBV‐47D11 regardless of patient demographics and baseline characteristics, however; because of the high inter‐individual variability and small sample size a statistical significance was not reached. There is potential for anti‐SARS‐CoV‐2 activity with ABBV‐47D11 doses of 600 mg or higher, which could be evaluated in future clinical trials designed and powered to assess viral load reductions and clinical benefit.