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Randomized Controlled Trial
. 2017 Oct 23;27(1):60.
doi: 10.1038/s41533-017-0059-1.

Comprehensive assessment of the safety of olodaterol 5 µg in the Respimat® device for maintenance treatment of COPD: comparison with the long-acting β2-agonist formoterol

Andrea Koch  1   2 , Henrik Watz  3 , M Reza Maleki-Yazdi  4 , Ulrich Bothner  5 , Kay Tetzlaff  5 , Florian Voß  5 , Lorcan McGarvey  6
Affiliations
Randomized Controlled Trial

Comprehensive assessment of the safety of olodaterol 5 µg in the Respimat® device for maintenance treatment of COPD: comparison with the long-acting β2-agonist formoterol

Andrea Koch et al. NPJ Prim Care Respir Med. .

Abstract

This analysis provides a comprehensive clinical assessment of the long-term safety of the licensed dose of olodaterol (5 µg once daily [QD] via Respimat® inhaler) in patients with chronic obstructive pulmonary disease by exploring the occurrence of acknowledged side effects of long-acting β2-agonists as well as those included in the olodaterol and formoterol labels. We analysed pooled data from two replicate, double-blind studies of olodaterol (5 µg QD via Respimat®) compared to formoterol (12 µg twice daily [BID]) or placebo over 48 weeks (1222.13, NCT00793624; 1222.14, NCT00796653). Patients could continue their background treatment. The analysis considered adverse events (AEs) typically associated with β2-agonists, including cardiovascular events, as well as administration-related events. Descriptive statistics were provided for the incidence of AEs and aggregated AEs. The analysis included 1379 patients: 460 placebo, 459 olodaterol and 460 formoterol; AEs were reported by 70.9, 71.7 and 69.1% of patients, respectively. Exposure-adjusted incidence rates of cardiac AEs (arrhythmia and myocardial ischaemia) and cough were numerically lower in the olodaterol group than the formoterol group, while nasopharyngitis, throat irritation, metabolism and psychiatric disorders were numerically higher in the olodaterol group. The most frequent event in the olodaterol group was nasopharyngitis (placebo 8.0%; olodaterol 12.9%; formoterol 10.0%). Except for cough (incidence rate ratio of 0.46 [95% confidence interval 0.24, 0.89] in favour of olodaterol), there were no significant differences between active groups. In conclusion, olodaterol 5 µg QD was well tolerated over 48 weeks with a typical β2-agonist safety profile comparable to formoterol 12 µg BID.

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Conflict of interest statement

A.K. has received a grant from Actelion Pharmaceuticals and has taken part in congresses for Boehringer Ingelheim, Almirall, Bayer, TEVA, Roche, Actelion and Novartis. H.W. reports personal fees for consulting and compensation for his institution during the conduct of the study from Boehringer Ingelheim related to the submitted work, and participation in advisory boards for Almirall, AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, in lectures for Almirall, AstraZeneca, Boehringer Ingelheim, BerlinChemie, GlaxoSmithKline, Novartis and Chiesi, and congress travel support from GlaxoSmithKline and Novartis outside the submitted work; his institution has also received compensation for the conduct of clinical studies from Almirall, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Chiesi, Takeda, AB2BIO, Bayer and Intermune outside the submitted work. M.R.M.-Y. declares that he has no competing financial interests. U.B., K.T. and F.V. are employees of Boehringer Ingelheim. L.M. reports personal fees from Applied Clinical Intelligence during the conduct of the study, grants from Asthma UK, NI Chest Heart & Stroke, NC3Rs, British Heart Foundation and Chiesi, travel and subsistence for attendance at scientific meetings from Boehringer Ingelheim, GlaxoSmithKline and Chiesi, and advisory board/consultancy fees from Almirall, NAPP, GlaxoSmithKline and Boehringer Ingelheim outside the submitted work.

Figures

Fig. 1
Fig. 1
Probability of discontinuation with placebo, olodaterol and formoterol. Cox regression analysis shows a significant difference from placebo for olodaterol 5 μg (P = 0.0013) and for formoterol treatment (P = 0.0180)
Fig. 2
Fig. 2
Overall incidence of adverse events (AEs)
Fig. 3
Fig. 3
Forest plot showing the exposure-adjusted rate and ratio for adverse events (AEs) of interest comparing olodaterol 5 µg with formoterol 12 µg. CI confidence interval
See this image and copyright information in PMC

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