美国艾尔建公司Joel M. Trugman联合爱因斯坦医学院Richard B. Lipton团队，比较了Ubrogepant与安慰剂用于偏头痛急性治疗的效果。这一研究成果2019年11月19日发表在国际顶尖学术期刊《美国医学会杂志》上。

Ubrogepant是一种口服降钙素基因相关肽受体拮抗剂，目前正研究将其用于偏头痛的急性治疗。

2016年8月26日至2018年2月26日，研究组在美国的99个医疗中心进行了一项临床3期、多中心、随机、双盲、安慰剂对照、单次给药的临床试验（ACHIEVE II），招募了1686名先兆性或无先兆偏头痛患者，每月发作2到8次。将这些发作时中重度疼痛的患者随机分为三组，其中562例口服Ubrogepant 50mg，561例口服Ubrogepant 25mg，563例口服安慰剂治疗。

最终有1355人完成试验并可评估疗效。Ubrogepant 50mg组464名患者中有101名（21.8%）服药2小时后疼痛缓解，Ubrogepant 25mg组435名患者中有90名（20.7%），安慰剂组456名患者中有65名（14.3%）。

Ubrogepant 50mg组463名患者中有180名（38.9%）服药2小时后最烦人的偏头痛相关症状消失，Ubrogepant 25mg组434名患者中有148名（34.1%），安慰剂组456名患者中有125名（27.4%）。48小时内最常见的不良反应为恶心和头晕，Ubrogepant 50mg组的发生率为2.0%和1.4%，Ubrogepant 25mg组为2.5%和2.1%，安慰剂组为2.0%和1.6%。

总之，与安慰剂相比，服用50mg和25mg Ubrogepant可显著提高2小时疼痛缓解率，服用50mg Ubrogepant可有效解除2小时最烦人的偏头痛相关症状。但关于该药的安全性仍需进一步研究。

附：英文原文

Title: Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial

Author: Richard B. Lipton, David W. Dodick, Jessica Ailani, Kaifeng Lu, Michelle Finnegan, Armin Szegedi, Joel M. Trugman

Issue&Volume: 2019/11/19

Abstract:

Importance  Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist under investigation for acute treatment of migraine.

Objective  To evaluate the efficacy and tolerability of ubrogepant compared with placebo for acute treatment of a single migraine attack.

Design, Setting, and Participants  Phase 3, multicenter, randomized, double-blind, placebo-controlled, single-attack, clinical trial (ACHIEVE II) conducted in the United States (99 primary care and research clinics; August 26, 2016-February 26, 2018). Participants were adults with migraine with or without aura experiencing 2 to 8 migraine attacks per month.

Interventions  Ubrogepant 50 mg (n = 562), ubrogepant 25 mg (n = 561), or placebo (n = 563) for a migraine attack of moderate or severe pain intensity.

Main Outcomes and Measures  Co-primary efficacy outcomes were pain freedom and absence of the participant-designated most bothersome migraine-associated symptom (among photophobia, phonophobia, and nausea) at 2 hours after taking the medication.

Results  Among 1686 randomized participants, 1465 received study treatment (safety population; mean age, 41.5 years; 90% female); 1355 of 1465 (92.5%) were evaluable for efficacy. Pain freedom at 2 hours was reported by 101 of 464 participants (21.8%) in the ubrogepant 50-mg group, 90 of 435 (20.7%) in the ubrogepant 25-mg group, and 65 of 456 (14.3%) in the placebo group (absolute difference for 50 mg vs placebo, 7.5%; 95% CI, 2.6%-12.5%; P = .01; 25 mg vs placebo, 6.4%; 95% CI, 1.5%-11.5%; P = .03). Absence of the most bothersome associated symptom at 2 hours was reported by 180 of 463 participants (38.9%) in the ubrogepant 50-mg group, 148 of 434 (34.1%) in the ubrogepant 25-mg group, and 125 of 456 (27.4%) in the placebo group (absolute difference for 50 mg vs placebo, 11.5%; 95% CI, 5.4%-17.5%; P = .01; 25 mg vs placebo, 6.7%; 95% CI, 0.6%-12.7%; P = .07). The most common adverse events within 48 hours of any dose were nausea (50 mg, 10 of 488 [2.0%]; 25 mg, 12 of 478 [2.5%]; and placebo, 10 of 499 [2.0%]) and dizziness (50 mg, 7 of 488 [1.4%]; 25 mg, 10 of 478 [2.1%]; placebo, 8 of 499 [1.6%]).

Conclusions and Relevance  Among adults with migraine, acute treatment with ubrogepant compared with placebo led to significantly greater rates of pain freedom at 2 hours with 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose. Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations.

DOI: 10.1001/jama.2019.16711

Source: https://jamanetwork.com/journals/jama/article-abstract/2755615