Inventi Impact: Pulmonology

Inventi:hln/17305/15

Randomised, Double-blind, Placebocontrolled Crossover Study to Investigate Different Dosing\nRegimens of Olodaterol Delivered via Respimat® in Patients with Moderate to Severe Persistent\nAsthma

Background: A Phase II, multicentre, randomised, double-blind, placebo-controlled, crossover trial comparing the\n24-h forced expiratory volume in 1 s (FEV1) time profile after 3 weeksââ?¬â?¢ treatment with once-daily (QD) or twice-daily\n(BID) olodaterol (at the same total daily dose) versus placebo delivered via RespimatÃ?® in patients with moderate to\nsevere asthma.\nMethods: Patients were randomised to different sequences of olodaterol with 2-week washout, either as a total\ndaily dose of 5 ?g (5 ?g QD [AM] or 2.5 ?g BID) or placebo, or 10 ?g (10 ?g QD [AM] or 5 ?g BID) or placebo.\nPrimary end point was FEV1 area under the curve from 0 to 24 h (AUC0ââ?¬â??24) response (defined as change from study\nbaseline FEV1) after 3 weeks. Key secondary end points were FEV1 AUC0ââ?¬â??12 and AUC12ââ?¬â??24 responses.\nResults: Two hundred and six patients received treatment. All olodaterol treatments demonstrated statistically\nsignificant improvements in FEV1 AUC0ââ?¬â??24 response at 3 weeks versus placebo (p < 0.0001); adjusted mean treatment\ndifference versus placebo was 0.191 L for olodaterol 2.5 ?g BID (95 % confidence interval [CI] 0.152, 0.229), 0.150 L for\n5 ?g QD (95 % CI 0.111, 0.189), 0.228 L for 5 ?g BID (95 % CI 0.190, 0.266) and 0.209 L for 10 ?g QD (95 % CI 0.170,\n0.247). These results were supported by the key secondary end points. Olodaterol 5 ?g QD provided numerically lower\nmean values for 24-h bronchodilation than olodaterol 2.5 ?g BID (p = 0.0465), with no statistically significant difference\nbetween treatment with olodaterol 10 ?g QD and 5 ?g BID. No relevant differences in morning and evening peak\nexpiratory flow or Asthma Control Questionnaire scores at 3 weeks were observed between different doses and\nregimens. Adverse events were generally mild to moderate and comparable between groups.\nConclusions: All doses and dose frequencies provided adequate 24-h bronchodilation superior to placebo. Based on\nthe results of this study, it would be reasonable to include both posologies of 5 ?g olodaterol daily (5 ?g QD or 2.5 ?g\nBID, both delivered in two puffs per dose from the RespimatÃ?® inhaler) in subsequent studies. Further studies are\nnecessary to confirm the optimum dosing regimen in asthma. No safety concerns were identified.