通过呼吸驱动吸入器与压力定量吸入器递送的布地奈德/福莫特罗的治疗等效性。

Therapeutic equivalence of budesonide/formoterol delivered via breath-actuated inhaler vs pMDI.

作者信息

Murphy Kevin R, Dhand Rajiv, Trudo Frank, Uryniak Tom, Aggarwal Ajay, Eckerwall Göran

机构信息

Allergy, Asthma, and Pulmonary Research, Boys Town National Research Hospital, Department of Pediatrics, University of Nebraska Medical Center, Creighton University School of Medicine, Omaha, NE 68132, United States.

Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, U114, Knoxville, TN 37920, United States.

出版信息

Respir Med. 2015 Feb;109(2):170-9. doi: 10.1016/j.rmed.2014.12.009. Epub 2015 Jan 3.

DOI:10.1016/j.rmed.2014.12.009

PMID:25596138

Abstract

RATIONALE

To assess equivalence of twice daily (bid) budesonide/formoterol (BUD/FM) 160/4.5 μg via breath-actuated metered-dose inhaler (BAI) versus pressurized metered-dose inhaler (pMDI).

METHODS

This 12-week, double-blind, multicenter, parallel-group study, randomized adolescents and adults (aged ≥12 years) with asthma (and ≥3 months daily use of inhaled corticosteroids) to BUD/FM BAI 2 × 160/4.5 μg bid, BUD/FM pMDI 2 × 160/4.5 μg bid, or BUD pMDI 2 × 160 μg bid. Inclusion required prebronchodilator forced expiratory volume in one second (FEV1) ≥45 to ≤85% predicted, and reversibility of ≥12% in FEV1 (ages 12 to <18 years) or ≥12% and 200 mL (ages ≥18 years). Confirmation that 60-min postdose FEV1 response to BUD/FM pMDI was superior to BUD pMDI was required before equivalence testing. Therapeutic equivalence was shown by treatment effect ratio of BUD/FM BAI vs BUD/FM pMDI on 60-min postdose FEV1 and predose FEV1 within confidence intervals (CIs) of 80-125%.

RESULTS

Mean age of 214 randomized patients was 42.7 years. BUD/FM pMDI was superior to BUD pMDI (60-min postdose FEV1 treatment effect ratio, 1.10; 95% CI, 1.06-1.14; p < 0.001). Treatment effect ratios for BUD/FM BAI versus pMDI for 60-min postdose FEV1 (1.01; 95% CI, 0.97-1.05) and predose FEV1 (1.03; 95% CI, 0.99-1.08) were within predetermined CIs for therapeutic equivalence. Adverse event profiles, tolerability, and patient-reported ease of use were similar.

CONCLUSIONS

BUD/FM 2 × 160/4.5 μg bid BAI is therapeutically equivalent to BUD/FM conventional pMDI. The introduction of BUD/FM BAI would expand options for delivering inhaled corticosteroid/long-acting β2-agonist combination therapy to patients with moderate-to-severe asthma. ClinicalTrials.gov NCT01360021.

摘要

原理

评估通过呼吸驱动定量吸入器（BAI）与压力定量吸入器（pMDI）每日两次（bid）使用布地奈德/福莫特罗（BUD/FM）160/4.5μg的等效性。

方法

这项为期12周的双盲、多中心、平行组研究，将患有哮喘（且每日使用吸入性糖皮质激素≥3个月）的青少年和成年人（年龄≥12岁）随机分为BUD/FM BAI 2×160/4.5μg bid组、BUD/FM pMDI 2×160/4.5μg bid组或BUD pMDI 2×160μg bid组。纳入标准要求支气管扩张剂前一秒用力呼气容积（FEV1）≥预计值的45%至≤85%，且FEV1的可逆性在12%以上（12至<18岁）或≥12%且增加200mL（年龄≥18岁）。在进行等效性测试之前，需要确认BUD/FM pMDI给药后60分钟的FEV1反应优于BUD pMDI。通过BUD/FM BAI与BUD/FM pMDI在给药后60分钟FEV1和给药前FEV1的治疗效果比在80%-125%的置信区间（CI）内来显示治疗等效性。

结果

214名随机分组患者的平均年龄为42.7岁。BUD/FM pMDI优于BUD pMDI（给药后60分钟FEV1治疗效果比，1.10；95%CI，1.06-1.14；p<0.001）。BUD/FM BAI与pMDI在给药后60分钟FEV1（1.01；95%CI，0.97-1.05）和给药前FEV1（1.03；95%CI，0.99-1.08）的治疗效果比在预先确定的治疗等效性CI范围内。不良事件谱、耐受性和患者报告的易用性相似。