Acute cardiovascular safety of two formulations of beclometasone dipropionate/formoterol fumarate in COPD patients: A single-dose, randomised, placebo-controlled crossover study

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• 作者：Dave Singh^a ; ^{DSingh@meu.org.uk} ; Giorgia Ciurlia^b ; Annalisa Piccinno^b ; Annamaria Muraro^b ; Maria Bocchi^b ; Mario Scuri^b
• 关键词：β2-agonist ; Cardiovascular ; Safety ; COPD
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：42
• 期：Complete
• 页码：43-51
• 全文大小：409 K
• 卷排序：42

文摘

An extrafine combination of beclometasone dipropionate (BDP) and formoterol fumarate (FF) via a pressurised metered-dose inhaler (pMDI) has been commercially available for some years for the management of asthma and chronic obstructive pulmonary disease (COPD). A dry powder inhaler (DPI) formulation of extrafine BDP/FF is now also available. This study evaluated the cardiovascular safety of BDP/FF DPI in comparison to BDP/FF pMDI and placebo.MethodsSingle-dose, partially-blind, randomised, placebo-controlled, 5-period crossover study. Main inclusion criteria: aged 40–75 years; moderate to severe COPD (post-bronchodilator FEV1 40–80% predicted, FEV1/FVC <0.7). Patients received BDP/FF 200/12, 800/48 μg and placebo via DPI, and BDP/FF 200/12 and 800/48 μg via pMDI. In both devices, 200/12 μg is the therapeutic dose; 800/48 μg is supratherapeutic.Primary objective: to demonstrate non-inferiority between BDP/FF DPI and pMDI in average 4-h heart rate (HR0–4h) at each dose level. Secondary variables included: HR0–12h, HR peak and individual timepoint; QTcF interval; SBP and DBP AUC0–12h; and potassium and glucose AUC0–4h. Adverse events (AEs) were collected.ResultsForty-nine patients were randomised; 45 (92%) received all five treatments. Non-inferiority was demonstrated between the DPI and pMDI formulations at both doses (−0.2 bpm [95% CI –1.3, 0.9] for 200/12 μg and 0.6 bpm [−0.5, 1.7] for 800/48 μg). Although there were statistically significant treatment-placebo differences at both doses and with both devices (thus confirming assay sensitivity), these differences were small and well below 5 bpm for the 200/12 μg dose. The results for the secondary parameters (QTcF, glucose and potassium) further supported the therapeutic equivalence of the two treatments. At the therapeutic dose, there were no clinically relevant treatment-placebo differences in any parameter with either formulation. There was no increase in the proportion of patients reporting AEs whilst receiving therapeutic doses of BDF/FF (either formulation) compared with placebo.ConclusionsOverall, this study provides reassurance over the cardiovascular safety of extrafine BDP/FF, both in a DPI and a pMDI formulation.