Safety and tolerability of ubrogepant for the acute treatment of migraine in participants taking atogepant for the preventive treatment of episodic migraine: Results from the TANDEM study.

Objective: To evaluate the safety and tolerability of ubrogepant for the acute treatment of migraine in participants taking atogepant for the preventive treatment of episodic migraine (EM).

Background: Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for the preventive treatment of migraine in adults and ubrogepant is an oral CGRP receptor antagonist approved for the acute treatment of migraine in adults, with or without aura. The safety and tolerability of the concomitant use of ubrogepant and atogepant have not been previously evaluated in a clinical setting.

Methods: The TANDEM study, a phase 4, two-period, multicenter, open-label study conducted in the United States, enrolled adults with migraine, with or without aura, and <15 headache days/month. In Treatment Period 1, participants took atogepant 60 mg once daily (QD) for 12 weeks and their own non-gepant acute headache medication for breakthrough migraine attacks. In Treatment Period 2, participants continued taking atogepant 60 mg QD and ubrogepant 100 mg was taken as needed (PRN) for the treatment of breakthrough migraine attacks (up to eight per 4-week interval) for 12 weeks. In Treatment Period 2, an optional second ubrogepant dose or the participant's own acute medication could be used to rescue headaches that did not resolve within 2-24 h post initial ubrogepant dose. The primary objective evaluated the safety and tolerability of the concomitant use of ubrogepant and atogepant.

Results: Of 263 participants enrolled, 262 were treated in Treatment Period 1 (Safety Population 1) and 218 continued and were treated in Treatment Period 2 (Safety Population 2). The mean (standard deviation) number of ubrogepant use days in Treatment Period 2 was 6.6 (5.03) over the 12 weeks. In Treatment Periods 1 and 2, 49.6% and 43.1% of participants experienced a treatment-emergent adverse event (TEAE), respectively. The most common TEAEs (≥5%) in Treatment Period 1 and Treatment Period 2 were COVID-19 (8.4%, 3.2%), fatigue (6.5%, 1.4%), nausea (6.1%, 0.9%), decreased appetite (5.7%, 0.9%), and constipation (5.3%, 0.9%). In Treatment Period 2, no increase in the incidence and types of TEAEs in relation to the number of ubrogepant use days or doses taken were identified. During the whole treatment period, 9.9% of participants discontinued atogepant or ubrogepant treatment due to TEAEs. There was one serious TEAE in Treatment Period 1 (ureterolithiasis) and one in Treatment Period 2 (cervical myelopathy), and both were considered not related to study treatment by the study investigators.

Conclusion: The use of atogepant 60 mg QD for the preventive treatment of EM and ubrogepant 100 mg PRN for the acute treatment of migraine over the 12-week open-label concomitant use treatment period was safe and well tolerated. The overall safety results were consistent with the known safety profiles of atogepant and ubrogepant when used alone and no new safety signals were identified.