Blumenfeld Andrew M, Boinpally Ramesh, De Abreu Ferreira Rosa, Trugman Joel M, Dabruzzo Brett, Ailani Jessica, Lipton Richard B
Headache Center of Southern California, Carlsbad, California, USA.
Clinical Pharmacology, AbbVie Inc., Madison, New Jersey, USA.
Headache. 2023 Mar;63(3):322-332. doi: 10.1111/head.14433. Epub 2023 Jan 5.
To evaluate potential drug-drug interactions of ubrogepant and atogepant.
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.
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.
Of the 31 participants enrolled, 26 completed the study. A single dose of ubrogepant had no statistically significant effect on atogepant pharmacokinetics. Co-administration 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.
The combination use of atogepant and ubrogepant was safe and well tolerated in adult participants with a history of migraine enrolled in the study. Pharmacokinetic changes during co-administration were not clinically meaningful.
评估ubrogepant与atogepant之间潜在的药物相互作用。
ubrogepant和atogepant是降钙素基因相关肽（CGRP）受体拮抗剂，最近分别被批准用于偏头痛的急性和预防性治疗。对于因偏头痛预防性治疗而开具atogepant的患者，医疗保健提供者可以开具ubrogepant用于突破性偏头痛发作的急性治疗。
对诊断为偏头痛至少1年的参与者进行了一项Ib期、多中心、开放标签、固定序列研究。为评估该I期试验中药代动力学相互作用的主要目标，使用了美国食品药品监督管理局批准的atogepant最高个体剂量强度（每日一次60mg）和ubrogepant（100mg），ubrogepant每3天按固定剂量方案给药，无论参与者是否正在经历偏头痛发作。次要终点包括安全性和耐受性。在整个研究过程中监测临床安全性指标。
在纳入的31名参与者中，26名完成了研究。单剂量ubrogepant对atogepant的药代动力学没有统计学上的显著影响。ubrogepant与atogepant联合给药导致ubrogepant血浆浓度-时间曲线下面积增加19%（几何平均比值118.80，90%置信区间[CI]108.69-129.84），ubrogepant最大血浆浓度增加26%（几何平均比值125.63，90%CI105.58-149.48）。这些ubrogepant暴露的统计学显著变化在临床上并无意义，且未发现该联合用药有新的安全性问题。
在本研究中纳入的有偏头痛病史的成年参与者中，atogepant和ubrogepant联合使用安全且耐受性良好。联合给药期间的药代动力学变化在临床上并无意义。
