Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4)

Roland Buhl, François Maltais, Roger Abrahams, Leif Bjermer, Eric Derom, Gary Ferguson, Matjaž Fležar, Jacques Hébert, Lorcan McGarvey, Emilio Pizzichini, Jim Reid, Antony Veale, Lars Grönke, Alan Hamilton, Lawrence Korducki, Kay Tetzlaff, Stella Waitere-Wijker, Henrik Watz, Eric Bateman, Roland Buhl, François Maltais, Roger Abrahams, Leif Bjermer, Eric Derom, Gary Ferguson, Matjaž Fležar, Jacques Hébert, Lorcan McGarvey, Emilio Pizzichini, Jim Reid, Antony Veale, Lars Grönke, Alan Hamilton, Lawrence Korducki, Kay Tetzlaff, Stella Waitere-Wijker, Henrik Watz, Eric Bateman

Abstract

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies. Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg. Incidence of adverse events was comparable between the FDCs and the mono-components. These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.

Trial registration: ClinicalTrials.gov NCT01431274 NCT01431287.

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside the online version of this article at erj.ersjournals.com

Copyright ©ERS 2015.

Figures

FIGURE 1
FIGURE 1
Study design (Study 1237.5: NCT01431274; Study 1237.6: NCT0143 1287). R: randomisation; FDC: fixed- dose combination. #: primary end-point assessment.
FIGURE 2
FIGURE 2
Patient disposition and flow in (a) Study 1237.5 and (b) Study 1237.6. Tio: tiotropium; Olo: olodaterol; FDC: fixed-dose combination. #: not due to adverse event.
FIGURE 3
FIGURE 3
Lung function end points (combined data set) over 52 weeks: full analysis set. a) adjusted mean trough forced expiratory volume in 1 s (FEV1); all comparisons of Tio+Olo 5/5 μg and 2.5/5 μg versus the monotherapies were statistically significant (p<0.001). b) FEV1 area under the curve from 0 to 3 h (AUC0–3); all comparisons of Tio+Olo 5/5 μg and 2.5/5 μg versus the monotherapies were statistically significant (p<0.01). Tio: tiotropium; Olo: olodaterol.

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