Efficacy and safety of combining olodaterol Respimat^® and tiotropium HandiHaler^® in patients with COPD: results of two randomized, double-blind, active-controlled studies

Abstract

Background

Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD). We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β₂-agonist olodaterol.

Methods

Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT1694771] and ANHELTO 2 [NCT1696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat^®) combined with tiotropium 18 μg once daily (via HandiHaler^®) versus tiotropium 18 μg once daily (via HandiHaler^®) combined with placebo (via Respimat^®) in patients with moderate to severe COPD. Primary efficacy end points were area under the curve from 0–3 hours of forced expiratory volume in 1 second (FEV₁ AUC_0–3) and trough FEV₁ after 12 weeks (for the individual trials). A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).

Results

Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV₁ AUC_0–3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV₁ (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points. These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001). The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.

Conclusion

These studies demonstrated that olodaterol (Respimat^®) and tiotropium (HandiHaler^®) provided bronchodilatory effects above tiotropium alone in patients with COPD. In general, both treatments were well tolerated.

Keywords:

• bronchodilator
• long-acting beta2-agonist
• long-acting muscarinic antagonist
• olodaterol Respimat^®
• tiotropium HandiHaler^®

Disclosure

Richard ZuWallack and Roger Abrahams received no compensation related to the development of the manuscript. Lisa Allen, Gemzel Hernandez, and Naitee Ting are employees of Boehringer Ingelheim Pharmaceuticals Inc. This work was supported by Boehringer Ingelheim Pharmaceuticals Inc. Medical writing assistance was provided by Rob Kite, BSc, of Complete HealthVizion, which was contracted and compensated by Boehringer Ingelheim Pharmaceuticals Inc. The authors declare no other conflicts of interest in this work.