Bronchodilator efficacy of tiotropium/formoterol (18/12 µg once daily via a Discair inhaler), tiotropium alone (18 µg by Handihaler) or combined with formoterol (12 µg twice daily by Aerolizer) in adults with moderate-to-severe stable COPD

Abstract

Objectives: The bronchodilator efficacy of a once-daily fixed-dose combination of tiotropium/formoterol (18/12 µg administered via a dry-powder inhaler, Discair) [TIO/FORM_fixed group] vs a single-dose of tiotropium (18 µg) by Handihaler¹ alone [TIO_mono group], or combined with formoterol 12 µg twice-daily by Aerolizer² [TIO/FORM_bid group] was compared in patients with moderate-to-severe stable COPD. Methods: COPD patients were randomized (28 patients/group) to receive TIO/FORM_fixed, TIO_mono, or TIO/FORM_bid. AUC for the changes in FEV₁ and FVC over a 24-h period; bronchodilator response (100 ml improvement in FEV₁) in the first 30 min; maximum changes in FEV₁ and FVC; and safety data were recorded. The primary endpoint was to confirm the non-inferiority of TIO/FORM_fixed vs TIO/FORM_bid in terms of the AUC for the changes in FEV₁ over a 24-h period. Results: Changes in AUC_0–24h for FEV₁ and FVC were similar for TIO/FORM_fixed and TIO/FORM_bid, and were superior to TIO_mono (p < 0.001). A positive bronchodilator response at 30 min was demonstrated in 50%, 64%, and 71% of patients in the TIO_mono, TIO/FORM_bid, and TIO/FORM_fixed groups, respectively (NS). Maximum FEV₁ and FVC changes were measured as 0.25/0.41 L, 0.32/0.49 L, and 0.37/0.53 L, for TIO_mono, TIO/FORM_bid, and TIO/FORM_fixed, respectively (FEV₁: TIO/FORM_fixed vs TIO_mono, p = 0.0017 and TIO/FORM_fixed vs TIO/FORM_bid, p = 0.4846); no differences were recorded between the combination groups. Conclusions: The 24-h bronchodilator efficacy of TIO/FORM_fixed 18/12 µg once-daily by Discair³ was non-inferior to a combination of tiotropium 18 µg by Handihaler plus formoterol 12 µg twice-daily by Aerolizer, and superior to tiotropium 18 µg monotherapy by Handihaler. Trial registration: ClinicalTrials.gov identifier: NCT02988869.