Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

Abstract

Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy. Patients received once-daily olodaterol 5 or 10 μg, twice-daily formoterol 12 μg, or placebo. Co-primary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0–3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George’s Respiratory Questionnaire. Overall, 904 (Study 1222.13) and 934 (Study 1222.14) patients received treatment. Olodaterol significantly improved FEV1 area under the curve from 0–3 hours versus placebo in both studies (with olodaterol 5 μg, 0.151 L and 0.129 L; with olodaterol 10 μg, 0.165 L and 0.154 L; for all comparisons P<0.0001) and FEV1 trough responses versus placebo (0.053–0.085 L; P<0.01), as did formoterol. Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo. Post hoc analysis using pattern mixture modeling (accounting for discontinuations) demonstrated statistical significance for olodaterol versus placebo. St George’s Respiratory Questionnaire total score was significantly improved with olodaterol, but not formoterol, versus placebo. No safety signals were identified from adverse-event or other safety data. Once-daily olodaterol 5 μg and 10 μg is efficacious in patients with moderate to very severe chronic obstructive pulmonary disease on usual-care maintenance therapy, with a satisfactory safety profile.

The 24-h lung-function profile of once-daily tiotropium and olodaterol fixed-dose combination in chronic obstructive pulmonary disease

“…Olodaterol is a novel once-daily long-acting b 2 -agonist (LABA) that is highly selective with nearly full intrinsic activity at b 2 receptors [7,8]. Phase III trials have demonstrated that olodaterol is effective at improving lung function over 24 h in patients with COPD [9e12] and, importantly, also provides improvements in patient-reported symptoms [11].…”

CTS position statement: Pharmacotherapy in patients with COPD—An update

“…We recommend the use of an inhaled long-acting bronchodilator, either LAMA or LABA monotherapy, to reduce dyspnea, improve exercise tolerance, and improve health status in stable COPD patients 32,33,37,38,40,44,[49][50][51][52][53][54][55][56][57][58][59][60] (Grade 1A). 2.…”

▼Olodaterol—another LABA for COPD

“…Four phase III clinical studies (trials 1222.11 to 1222.14) of long-term efficacy and safety were used to support licensing applications in the USA and Europe 18–20. In addition, four studies examined the effect on 24-hour lung function over 6 weeks of treatment (trials 1222.24, 1222.25, 1222.39 and 1222.40) 13,21.…”

“…The pivotal phase III randomised double-blind placebo-controlled parallel group studies compared olodaterol 5μg and 10μg with placebo19,20 and inhaled formoterol 12μg twice daily20 over 48 weeks. Although the prespecified primary outcome in each study was between olodaterol and placebo, the final sample size was based on the requirements for the comparison between olodaterol and formoterol.…”

“…Although the prespecified primary outcome in each study was between olodaterol and placebo, the final sample size was based on the requirements for the comparison between olodaterol and formoterol. The primary outcome measures assessed lung function, FEV 1 between 0–3 hours expressed as the area under the time-FEV 1 curve (FEV 1 AUC 0–3 ) and trough FEV 1 at 12 weeks or 24 weeks 19,20. In addition, two trials included the Transitional Dyspnoea Index (TDI) focal score at 24 weeks as a primary outcome and the St. George's Respiratory Questionnaire (SGRQ) total score as a key secondary outcome 20.…”