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

doi:10.1183/09031936.00136014

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

Eur Respir J. 2015 Apr;45(4):969-79. doi: 10.1183/09031936.00136014. Epub 2015 Jan 8.

Authors

Roland Buhl¹, François Maltais², Roger Abrahams³, Leif Bjermer⁴, Eric Derom⁵, Gary Ferguson⁶, Matjaž Fležar⁷, Jacques Hébert⁸, Lorcan McGarvey⁹, Emilio Pizzichini¹⁰, Jim Reid¹¹, Antony Veale¹², Lars Grönke¹³, Alan Hamilton¹⁴, Lawrence Korducki¹⁵, Kay Tetzlaff¹⁶, Stella Waitere-Wijker¹⁷, Henrik Watz¹⁸, Eric Bateman¹⁹

Affiliations

¹ Pulmonary Department, Mainz University Hospital, Mainz, Germany r.buhl@3-med.klinik.uni-mainz.de.
² Département de Médecine, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada.
³ Department of Clinical Research, Morgantown Pulmonary Associates, Morgantown, WV, USA.
⁴ Department of Respiratory Medicine and Allergology, Lund University, Lund, Sweden.
⁵ Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
⁶ Pulmonary Research Institute of Southeast Michigan, Livonia, MI, USA.
⁷ Klinika Golnik, Golnik, Slovenia.
⁸ Department of Medicine, Centre de Recherche Appliquée en Allergie de Québec (CRAAQ), Québec, Canada.
⁹ Department of Medicine, Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
¹⁰ Department of Pulmonology, NUPAIVA (Asthma Research Centre), Universidade Federal de Santa Catarina, Santa Catarina, Brazil.
¹¹ Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
¹² Department of Respiratory Medicine, The Queen Elizabeth Hospital, Adelaide, Australia.
¹³ Department of Medical Affairs Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
¹⁴ Medical Department, Boehringer Ingelheim, Burlington, Ontario, Canada.
¹⁵ Department of Biostatistics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
¹⁶ Department of Medical Affairs Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Department of Sports Medicine, Medical Clinic V, University of Tübingen, Tübingen, Germany.
¹⁷ Medical Department, Boehringer Ingelheim B.V., Alkmaar, The Netherlands.
¹⁸ Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany.
¹⁹ Division of Pulmonology, Department of Medicine, University of Cape Town Lung Institute, Cape Town, South Africa.

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.

Publication types

Clinical Trial, Phase III
Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Inhalation
Aged
Benzoxazines / administration & dosage*
Bronchodilator Agents / administration & dosage*
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Drug Therapy, Combination
Female
Follow-Up Studies
Humans
Internationality
Male
Maximum Tolerated Dose
Metered Dose Inhalers*
Middle Aged
Pulmonary Disease, Chronic Obstructive / diagnosis
Pulmonary Disease, Chronic Obstructive / drug therapy*
Risk Assessment
Severity of Illness Index
Spirometry
Tiotropium Bromide / administration & dosage*
Treatment Outcome

Substances

Benzoxazines
Bronchodilator Agents
olodaterol
Tiotropium Bromide

Associated data

ClinicalTrials.gov/NCT01431274
ClinicalTrials.gov/NCT01431287