Safety of once-daily tiotropium and olodaterol fixed-dose combination via the Respimat in chronic obstructive pulmonary disease in two 1-year studies

Introduction: The fixed-dose combination (FDC) of tiotropium (T), a once-daily long-acting muscarinic antagonist, and olodaterol (O), a once-daily long-acting ß2-agonist, is currently being evaluated in chronic obstructive pulmonary disease (COPD). Two 52-week, Phase III replicate pivotal studies were conducted to assess the efficacy and safety of FDCs of T and O (T+O) delivered via Respimat Soft Mist inhaler in patients (pts) with GOLD Stage 2 – 4 COPD. Pooled safety data from the two studies are presented here.

Methods: These were double-blind, randomised, parallel-group studies with 5 arms: O 5 µg, T 2.5 µg, T 5 µg, T+O 2.5/5 µg, T+O 5/5 µg. Key inclusion criteria were: age= 40 years, diagnosis of COPD, smoking history > 10 pack-years. Pts with a history of asthma or significant disease other than COPD were excluded. Adverse events (AEs) were reported throughout the studies.

Results: A total of 5162 pts were randomised and treated.

*MedDRA SOC
		Pts with AE, %
	O5 µg	T	T5 µg	T+O	T+O
	n = 1038	2.5 µg	n = 1033	2.5/5 µg	5/5 µg
		n = 1032		n = 1030	n = 1029
Total AEs	76.6	73.4	73.3	74.7	74.0
Serious AEs	17.4	15.1	16.7	16.3	16.4
Fatal AEs	1.3	1.2	1.6	1.4	1.7
Cardiac disorders*	5.7	5.8	5.3	5.8	4.5
Respiratory, thoracic and mediastinal disorders*	45.3	43.9	42.7	38.2	39.4

In general, AEs, serious AEs and fatal AEs were balanced across treatment groups. In particular, frequencies of AEs in the cardiac disorders System Organ Class (SOC) and respiratory disorders SOC were similar.

Conclusions: T+O FDCs were safe and well tolerated. In comparison to the individual components, there was no notable increase in AEs with T+O FDCs.

Funding: Boehringer Ingelheim.

Presented at ERS congress meeting 2014