M Reza Maleki-Yazdi1, Ekkehard Beck2, Alan L Hamilton3, Lawrence Korducki4, Paul Koker4, Charles Fogarty5. 1. Division of Respiratory Medicine, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address: maleki.pccrc@on.aibn.com. 2. Medical Department, Institut für Gesundheitsförderung, Rüdersdorf, Brandenburg, Germany. 3. Boehringer Ingelheim (Canada) Ltd, Burlington, Ontario, Canada. 4. Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA. 5. Spartanburg Medical Research, Spartanburg, SC, USA.
Abstract
BACKGROUND: Olodaterol is a novel long-acting β2-agonist (LABA) with ≥24-h duration of action in preclinical and clinical studies. OBJECTIVE: This Phase II, multicentre, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study evaluated four doses of once-daily olodaterol over 4 weeks in patients with chronic obstructive pulmonary disease (COPD), based on efficacy, safety and pharmacokinetic parameters. METHODS: Patients received olodaterol inhalation solution or placebo via Respimat® Soft Mist™ inhaler once daily for 4 weeks. Pulmonary function testing was performed pre-dose (trough) and up to 3 or 6 h post-dose, depending on visit. Primary end point was change from baseline in trough forced expiratory volume in 1 s (FEV1) after 4 weeks' treatment. Secondary end points included change from baseline in peak FEV1 and FEV1 area under the curve from 0 to 6 h. RESULTS:405 patients with COPD were randomised and assigned to treatment. Mean baseline post-bronchodilator FEV1 was 1.50 L (54% predicted). All olodaterol doses provided statistically significant increases in trough FEV1 compared to placebo (2 μg: 0.061 L [p = 0.0233]; 5 μg: 0.097 L [p = 0.0003]; 10 μg: 0.123 L [p < 0.0001]; 20 μg: 0.132 L [p < 0.0001]). A clear dose-response relationship was demonstrated regarding pulmonary function; the two highest olodaterol doses (10 and 20 μg) formed the plateau of the dose-response curve. All olodaterol doses were well tolerated, with no dose-dependent safety effects. CONCLUSION: Once-daily olodaterol demonstrated 24-h bronchodilator efficacy, confirming its potential as a once-daily LABA for the management of COPD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00452400.
RCT Entities:
BACKGROUND:Olodaterol is a novel long-acting β2-agonist (LABA) with ≥24-h duration of action in preclinical and clinical studies. OBJECTIVE: This Phase II, multicentre, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study evaluated four doses of once-daily olodaterol over 4 weeks in patients with chronic obstructive pulmonary disease (COPD), based on efficacy, safety and pharmacokinetic parameters. METHODS:Patients received olodaterol inhalation solution or placebo via Respimat® Soft Mist™ inhaler once daily for 4 weeks. Pulmonary function testing was performed pre-dose (trough) and up to 3 or 6 h post-dose, depending on visit. Primary end point was change from baseline in trough forced expiratory volume in 1 s (FEV1) after 4 weeks' treatment. Secondary end points included change from baseline in peak FEV1 and FEV1 area under the curve from 0 to 6 h. RESULTS: 405 patients with COPD were randomised and assigned to treatment. Mean baseline post-bronchodilator FEV1 was 1.50 L (54% predicted). All olodaterol doses provided statistically significant increases in trough FEV1 compared to placebo (2 μg: 0.061 L [p = 0.0233]; 5 μg: 0.097 L [p = 0.0003]; 10 μg: 0.123 L [p < 0.0001]; 20 μg: 0.132 L [p < 0.0001]). A clear dose-response relationship was demonstrated regarding pulmonary function; the two highest olodaterol doses (10 and 20 μg) formed the plateau of the dose-response curve. All olodaterol doses were well tolerated, with no dose-dependent safety effects. CONCLUSION: Once-daily olodaterol demonstrated 24-h bronchodilator efficacy, confirming its potential as a once-daily LABA for the management of COPD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00452400.
Authors: Stefan Andreas; Ulrich Bothner; Alberto de la Hoz; Isabel Kloer; Matthias Trampisch; Peter Alter Journal: Int J Chron Obstruct Pulmon Dis Date: 2020-08-10