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/FORMfixed group] vs a single-dose of tiotropium (18 µg) by Handihaler1 alone [TIOmono group], or combined with formoterol 12 µg twice-daily by Aerolizer2 [TIO/FORMbid group] was compared in patients with moderate-to-severe stable COPD.Methods: COPD patients were randomized (28 patients/group) to receive TIO/FORMfixed, TIOmono, or TIO/FORMbid.  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/FORMfixed vs TIO/FORMbid in terms of the AUC for the changes in FEV1 over a 24-h period. Results: Changes in AUC0-24h for FEV1 and FVC were similar for TIO/FORMfixed and TIO/FORMbid, and were superior to TIOmono (p < 0.001).  A positive bronchodilator response at 30 min was demonstrated in 50%, 64%, and 71% of patients in the TIOmono, TIO/FORMbid, and TIO/FORMfixed 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 TIOmono, TIO/FORMbid, and TIO/FORMfixed, respectively (FEV1: TIO/FORMfixed vs TIOmono, p = 0.0017 and TIO/FORMfixed vs TIO/FORMbid, p = 0.4846); no differences were recorded between the combination groups. Conclusions: The 24-h bronchodilator efficacy of TIO/FORMfixed 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.