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.

Keywords:

• COPD
• formoterol
• tiotropium
• bronchodilator efficacy
• fixed-dose combination

Transparency

Declaration of funding

This study was funded by Neutec Ar-Ge San & Tic A.S., Turkey (who developed the formulation Tioform, administered by Discair inhaler and manufactured by Neutec Inhaler Ilac San. Tic. A.S.).

Declaration of financial/other relationships

The authors received research support from Neutec Ar-Ge San. & Tic. A.S. (Turkey). None of the authors have received personal funding (salary) from Neutec. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors thank Neutec Ar-Ge San & Tic A.S. Clinical Research Department and Content Ed Net who provided help with medical writing funded by Neutec Ar-Ge San & Tic A.S (Turkey).

Notes

1 Handihaler, Boehringer Ingelheim Pharma GmbH & Co., KG Ingelheim am Rhein, Germany.

2 Aerolizer, Novartis Pharma Stein AG, Switzerland.

3 Discair, Neutec inhaler ilac San. ve Tic. A.S., Adapazari, Turkey.