Randomised, double-blind, placebo-controlled crossover study to investigate different dosing regimens of olodaterol delivered via Respimat® in patients with moderate to severe persistent asthma. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Beeh, Kai-Michael; LaForce, Craig; Gahlemann, Martina; Wenz, Arne; Toorawa, Robert; Fležar, Matjaž
• Is Part Of: Respiratory research. Volume 16:Issue 1(2015)
• Page Start: 1
• Page End: 12
• Publication Date: 2015-12
• Subjects: Olodaterol -- Long-acting beta-2-agonist -- Asthma; Respiratory organs -- Diseases -- Periodicals; 616.2005
• DOI: 10.1186/s12931-015-0243-1
• Languages: English
• ISSNs: 1465-993X

Abstract

Abstract Background A Phase II, multicentre, randomised, double-blind, placebo-controlled, crossover trial comparing the 24-h forced expiratory volume in 1 s (FEV1 ) time profile after 3 weeks' treatment with once-daily (QD) or twice-daily (BID) olodaterol (at the same total daily dose) versus placebo delivered via Respimat® in patients with moderate to severe asthma. Methods Patients were randomised to different sequences of olodaterol with 2-week washout, either as a total daily dose of 5 μg (5 μg QD [AM] or 2.5 μg BID) or placebo, or 10 μg (10 μg QD [AM] or 5 μg BID) or placebo. Primary end point was FEV1 area under the curve from 0 to 24 h (AUC0–24 ) response (defined as change from study baseline FEV1 ) after 3 weeks. Key secondary end points were FEV1 AUC0–12 and AUC12–24 responses. Results Two hundred and six patients received treatment. All olodaterol treatments demonstrated statistically significant improvements in FEV1 AUC0–24 response at 3 weeks versus placebo (p < 0.0001); adjusted mean treatment difference versus placebo was 0.191 L for olodaterol 2.5 μg BID (95 % confidence interval [CI] 0.152, 0.229), 0.150 L for 5 μg QD (95 % CI 0.111, 0.189), 0.228 L for 5 μg BID (95 % CI 0.190, 0.266) and 0.209 L for 10 μg QD (95 % CI 0.170, 0.247). These results were supported by the key secondary end points. Olodaterol 5 μg QD provided numerically lower mean values for 24-h bronchodilation than olodaterol 2.5 μg BID (p = 0.0465), with no statistically significant difference between treatment with olodaterol 10 μg QD and 5 μg BID. No relevant differences in morning and evening peak expiratory flow or Asthma Control Questionnaire scores at 3 weeks were observed between different doses and regimens. Adverse events were generally mild to moderate and comparable between groups. Conclusions All doses and dose frequencies provided adequate 24-h bronchodilation superior to placebo. Based on the results of this study, it would be reasonable to include both posologies of 5 μg olodaterol daily (5 μg QD or 2.5 μg BID, both delivered in two puffs per dose from the Respimat® inhaler) in subsequent studies. Further studies are necessary to confirm the optimum dosing regimen in asthma. No safety concerns were identified. Trial registration ClinicalTrials.govNCT01311661