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 mu g administered via a dry-powder inhaler, Discair) [TIO/FORMfixed group] vs a single-dose of tiotropium (18 mu g) by Handihaler(1) alone [TIOmono group], or combined with formoterol 12 mu g twice-daily by Aerolizer(2) [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 AUC(0-24h) 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 mu g once-daily by Discair(3) was non-inferior to a combination of tiotropium 18 mu g by Handihaler plus formoterol 12 mu g twice-daily by Aerolizer, and superior to tiotropium 18 mu g monotherapy by Handihaler.