To evaluate the safety and tolerability of Lu AG09222 when co-administered with ubrogepant.

Lu AG09222 is an anti-pituitary adenylate cyclase-activating polypeptide (PACAP) monoclonal antibody in development for the preventive treatment of migraine. Demonstrating compatibility with commonly used acute migraine treatments is important to ensure its suitability for a broad migraine population; this trial assessed co-administration with ubrogepant, an approved gepant medication.

Randomized, double-blind, placebo-controlled trial at 4 US sites. Adults aged 18–65 years (n=43) with episodic migraine (≥2 monthly migraine days, <15 headache days/month) were randomly assigned 1:1 to a single 300-mg subcutaneous dose of Lu AG09222 or placebo on Day 8. Ubrogepant dosing was 2×100 mg on Day 1 (i.e., the maximum dose in a 24-hour period) before Lu AG09222 or placebo, then 2×100 mg on Day 12 and 13 and 1×100 mg on Day 14 and 15. Endpoints included treatment-emergent adverse events (TEAEs), clinical safety laboratory tests, electrocardiogram (ECG), vital signs, anti-drug antibodies (ADA), and ubrogepant pharmacokinetic parameters. Safety follow-up was 12 weeks after administration of Lu AG09222 or placebo.

All TEAEs were mild, transient, non-serious, and none led to withdrawal. The TEAE frequency was similar for Lu AG09222 and placebo groups during the co-administration period. No clinically meaningful trends in vital signs, ECG, clinical laboratory tests, or hypersensitivity were identified. No ADA-related hypersensitivity reactions were reported. Ubrogepant pharmacokinetics (geometric means of C_MAX, ratio on Day 12 vs Day 1 and similarly for AUC_0-inf) were not influenced in a clinically meaningful way by Lu AG09222.

Lu AG09222 was well tolerated when co-administered with ubrogepant and did not alter ubrogepant pharmacokinetics. These data, together with similar results for co-administration with triptans presented previously, support the safety profile of Lu AG09222 for co-administration with common acute migraine therapies.