Abstract Details

Ubrogepant, an approved acute treatment for migraine in adults, is used to treat breakthrough attacks in patients receiving preventive treatment.

To examine pharmacokinetics (PK), safety, and tolerability of ubrogepant following coadministration with monoclonal antibody (mAb) preventive treatments, erenumab or galcanezumab.

This open-label, multicenter trial enrolled adults diagnosed for ≥1 year with migraine not on preventive treatment. Participants were assigned to an erenumab arm or galcanezumab arm. In each arm, participants received ubrogepant 100mg on day 1 (without a mAb). On day 8, participants received the assigned mAb: single subcutaneous (SC) erenumab 140mg injection or galcanezumab 240mg (2 SC 120mg injections). Ubrogepant 100mg was administered once daily on days 12–15. PK parameters of ubrogepant were assessed on days 1 and 12. Participants were followed for 30 days. 

Forty participants enrolled (20 per arm). Ubrogepant peak plasma concentration (C_max), area under the concentration-time curve from time 0 to t (AUC_0-t), and to infinity (AUC_0-∞) were minimally elevated after erenumab administration. With/without erenumab, median ubrogepant time to C_max (t_max) was 1.5 h; apparent terminal half-life (t_1/2) was similar with (5.3 h) and without (4.6 h) erenumab. With galcanezumab coadministration, ubrogepant C_max was unchanged while AUC_0-t and AUC_0-∞ were 5% higher. Ubrogepant t_max was 1.5 h; t_1/2 was similar with (5.0 h) and without (4.6 h) galcanezumab. No serious adverse events (AEs) or AEs leading to discontinuation were reported. In the erenumab arm, treatment-emergent AEs (TEAEs) were reported by 7/20 participants receiving ubrogepant alone, 8/19 with erenumab, and 7/19 with ubrogepant+erenumab. In the galcanezumab arm, TEAEs were reported by 2/20 participants receiving ubrogepant alone, 3/20 with galcanezumab, and 4/19 with ubrogepant+galcanezumab. No clinically relevant changes in laboratory parameters, vital signs, or electrocardiogram values were observed.

Ubrogepant PK was unchanged when coadministered with erenumab or galcanezumab. No safety concerns were identified.