Purpose: The pivotal CAPTAIN study reported a favorable safety profile with once-daily inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β₂-agonist (ICS/LAMA/LABA) triple combination of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in patients with inadequately controlled asthma, some of whom were Japanese. Here, we evaluate the long-term (52 weeks) safety of FF/UMEC/VI in Japanese patients with asthma.
Patients and Methods: This was a Phase III, 52-week, multicenter, non-comparator, non-randomized, open-label study (NCT03184987) in Japanese adults receiving maintenance therapy with ICS/LABA, with or without LAMA. At enrollment, patients were allocated to either FF/UMEC/VI 100/62.5/25mcg (Group 1) or 200/62.5/25mcg (Group 2). Patients in Group 1 could have their treatment stepped up to 200/62.5/25mcg at Week 24 if their Asthma Control Questionnaire (ACQ)-7 score was > 0.75. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs). Secondary endpoints included vital signs, electrocardiogram measurements, and clinical laboratory tests (biochemistry, hematology, urinalysis). Efficacy was assessed as “other” endpoints.
Results: A total of 111 Japanese patients were included in the intention-to-treat (ITT) population. Overall, 77 (69%) patients reported ≥ 1 AE (Group 1: n=30 [64%]; step-up group: n=7 [78%]; Group 2: n=40 [73%]). SAEs were reported for 1 (2.1%) and 2 (3.6%) patients in Groups 1 and 2, respectively. All SAEs were considered unrelated to study treatment. One AE and one SAE led to study withdrawal: oropharyngeal discomfort (Group 1); eosinophilic granulomatosis with polyangiitis (Group 2). No new safety concerns were identified throughout the 52-week treatment period.
Conclusion: In this uncontrolled open-label study, no new safety concerns were observed with long-term (52 weeks) treatment with once-daily FF/UMEC/VI among 111 Japanese patients with asthma.

Keywords: asthma, inhalers, Japan, safety, treatment outcome


中文翻译：

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日本哮喘患者每日一次单吸入器三联疗法糠酸氟替卡松/Umeclidinium/Vilanterol 的安全性：一项长期（52 周）III 期开放标签研究


目的：关键的 CAPTAIN 研究报告了每日一次吸入皮质类固醇/长效毒蕈碱拮抗剂/长效_β2激动剂 (ICS/LAMA/LABA) 糠酸氟替卡松/umeclidinium/维兰特罗 (FF/ UMEC/VI）治疗哮喘控制不佳的患者，其中一些是日本人。在此，我们评估 FF/UMEC/VI 在日本哮喘患者中的长期（52 周）安全性。

患者和方法：这是一项为期 52 周、多中心、非对照、非随机、开放标签的 III 期研究 (NCT03184987)，研究对象为接受 ICS/LABA 维持治疗（联合或不联合 LAMA）的日本成人。入组时，患者被分配至 FF/UMEC/VI 100/62.5/25mcg（第 1 组）或 200/62.5/25mcg（第 2 组）。如果第 1 组患者的哮喘控制问卷 (ACQ)-7 评分为 > 0.75，则第 24 周时治疗剂量可增加至 200/62.5/25mcg。主要终点是不良事件 (AE) 和严重 AE (SAE) 的发生率。次要终点包括生命体征、心电图测量和临床实验室测试（生物化学、血液学、尿液分析）。功效被评估为“其他”终点。

结果：总共 111 名日本患者被纳入意向治疗 (ITT) 人群。总体而言，77 名 (69%) 患者报告 ≥ 1 次 AE（第 1 组：n=30 [64%]；升级组：n=7 [78%]；第 2 组：n=40 [73%]）。第 1 组和第 2 组中分别有 1 名 (2.1%) 和 2 名 (3.6%) 患者报告了 SAE。所有 SAE 均被认为与研究治疗无关。一项 AE 和一项 SAE 导致研究退出：口咽不适（第 1 组）；嗜酸性肉芽肿伴多血管炎（第 2 组）。在整个 52 周的治疗期间没有发现新的安全问题。

结论：在这项非对照开放标签研究中，111 名日本哮喘患者接受每日一次 FF/UMEC/VI 长期（52 周）治疗，没有观察到新的安全问题。


关键词：哮喘、吸入器、日本、安全性、治疗结果