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

Abstract

Richard ZuWallack,1 Lisa Allen,2 Gemzel Hernandez,2 Naitee Ting,2 Roger Abrahams3 1Saint Francis Hospital and Medical Center, Hartford, CT, USA; 2Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 3Morgantown Pulmonary Associates, Morgantown, WV, USABackground: 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 [NCT01694771] and ANHELTO 2 [NCT01696058]) 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 AUC0–3) 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 AUC0–3 (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®