Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2-4 COPD: results from two replicate 48-week studies

Abstract

Background: Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile. Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy.

Methods: Patients received olodaterol 5 μg or 10 μg or placebo once daily for 48 weeks. Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response (change from baseline), and trough FEV1 response at 12 weeks. Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks.

Results: Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively. In both studies, olodaterol 5 μg and 10 μg significantly improved the FEV1 AUC0-3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo. Secondary end points supported the efficacy of olodaterol.

Conclusion: These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 μg and 10 μg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy.

Trial registration: ClinicalTrials.gov NCT00782210 NCT00782509.

Keywords: bronchodilator; chronic obstructive pulmonary disease; olodaterol.

Figure 1

Trial design for studies 1222.11 and 1222.12. Abbreviation: QD, once daily.

Figure 2

Participant flow in study 1222.11 (A) and study 1222.12 (B). Notes: ^aOne patient not treated because electrocardiogram was reviewed after randomization and was abnormal; ^bone patient was excluded due to lack of Health Insurance Portability and Accountability Act authorization; one patient discontinued prior to first drug dose. Abbreviation: QD, once daily.

Figure 3

FEV₁ AUC_0–3 (A) and trough FEV₁ (B) over 48 weeks in study 1222.11 and study 1222.12. Abbreviations: FEV₁, forced expiratory volume in 1 second; AUC_0–3, area under the curve from 0–3 hours.

Figure 4

FEV₁ over time from 1 hour pre-dose to 3 hours post-dose in study 1222.11 and study 1222.12 at day 1 (A) and week 12 (B). Abbreviations: FEV₁, forced expiratory volume in 1 second; h, hours.