Joan and Sanford Weill Department of Internal Medicine, Weill Cornell Medicine, New York, NY.
LungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; and Department of Medicine, Christian-Albrechts University Kiel, Kiel, Germany.
Chest. 2017 Feb;151(2):340-357. doi: 10.1016/j.chest.2016.11.028. Epub 2016 Dec 1.
Long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) combinations are a treatment option for patients with COPD who continue to have symptoms despite treatment with a LAMA or a LABA alone. The Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-1) (NCT01854645) and the Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-2) (NCT01854658) trials investigated the efficacy and safety of a novel glycopyrrolate [GP]/formoterol [FF] 18/9.6-μg (GFF) metered dose inhaler (MDI) formulated using the Co-Suspension Delivery Technology in patients with moderate-to-very severe COPD.
These two phase III trials took place over 24 weeks and were randomized, double blind, and placebo controlled; 2,103 and 1,615 patients (40-80 years of age), respectively, were randomized. Patients received GFF MDI, GP MDI 18 μg, FF MDI 9.6 μg, or placebo MDI (all twice daily), or tiotropium 18 μg dry powder inhaler (once daily in PINNACLE-1 only [open-label active comparator]). Efficacy and safety were assessed.
At week 24, differences in change from baseline in the morning predose trough FEV for GFF MDI vs placebo MDI, GP MDI, and FF MDI were 150 mL, 59 mL, and 64 mL in PINNACLE-1 (all P < .0001) and 103 mL, 54 mL, and 56 mL in PINNACLE-2 (all P < .001), respectively. There were no significant safety findings (incidence of adverse events was similar between treatment arms).
We conclude that GFF MDI 18/9.6 μg demonstrated superiority over placebo and monocomponent MDIs and was well tolerated, thus providing an additional treatment option for patients with moderate-to-very severe COPD.
ClinicalTrials.gov; No.: NCT01854645 and No. NCT01854658; URL: www.clinicaltrials.gov.
长效毒蕈碱拮抗剂（LAMA）/长效β-激动剂（LABA）联合治疗是一种治疗选择，适用于尽管单独使用 LAMA 或 LABA 治疗后仍有症状的 COPD 患者。在中度至重度 COPD 患者中评估 PT003、PT005 和 PT001 的疗效和安全性的多中心研究（PINNACLE-1）（NCT01854645）和在中度至重度 COPD 患者中评估 PT003、PT005 和 PT001 的疗效和安全性的多中心研究（PINNACLE-2）（NCT01854658）试验研究了一种新型吡咯烷酮 [GP]/福莫特罗 [FF] 18/9.6-μg（GFF）计量吸入器（MDI）在中度至重度 COPD 患者中的疗效和安全性，该药物采用悬浮液输送技术配制。
这两项为期 24 周的 III 期试验为随机、双盲、安慰剂对照试验；分别有 2103 名和 1615 名（40-80 岁）患者接受 GFF MDI、GP MDI 18μg、FF MDI 9.6μg 或安慰剂 MDI（均每日两次），或噻托溴铵 18μg 干粉吸入器（仅在 PINNACLE-1 中每日一次[开放标签活性对照]）。评估了疗效和安全性。
在第 24 周，与安慰剂 MDI、GP MDI 和 FF MDI 相比，GFF MDI 与基线相比，清晨预剂量谷值 FEV 的变化在 PINNACLE-1 中分别为 150mL、59mL 和 64mL（均 P<.0001），在 PINNACLE-2 中分别为 103mL、54mL 和 56mL（均 P<.001）。未发现明显的安全性发现（治疗组之间不良事件的发生率相似）。
我们得出结论，GFF MDI 18/9.6μg 优于安慰剂和单成分 MDI，且耐受性良好，因此为中重度 COPD 患者提供了另一种治疗选择。
ClinicalTrials.gov；编号：NCT01854645 和 NCT01854658；网址：www.clinicaltrials.gov。
