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.

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 Handihaler ¹ alone [TIO _mono group], or combined with formoterol 12 µg twice-daily by Aerolizer ² [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 FEV ₁ and FVC over a 24-h period; bronchodilator response (100 ml improvement in FEV ₁ ) in the first 30 min; maximum changes in FEV ₁ 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 FEV ₁ over a 24-h period. Results: Changes in AUC _0-24h for FEV ₁ 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 FEV ₁ 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 (FEV ₁ : 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 Discair ³ 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.