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 CMAX, ratio on Day 12 vs Day 1 and similarly for AUC0-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.