Randomized, Double-Blind, Dose-Finding Study for Tiotropium when Added to Olodaterol, Administered via the Respimat® Inhaler in Patients with Chronic Obstructive Pulmonary Disease.

Abstract

INTRODUCTION:

Combining long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) is beneficial in chronic obstructive pulmonary disease (COPD), as the two classes of bronchodilator have complementary modes of action. The optimal dose for the fixed-dose combination of the LAMA tiotropium and the LABA olodaterol needed to be determined. In this phase II trial, the dose response of tiotropium on top of olodaterol was investigated in a free-dose combination, while other phase II studies have explored different doses of olodaterol on top of tiotropium, with both drugs delivered using the Respimat(®) inhaler.

METHODS:

This was a double-blind incomplete crossover trial in which 233 patients with moderate or severe COPD were randomized to receive four out of eight free-dose combinations of olodaterol (5 or 10 µg) and tiotropium (1.25, 2.5, or 5 µg) or placebo for 4 weeks each. Primary end point was trough forced expiratory volume in 1 s (FEV1) change from baseline (response) after 4 weeks.

RESULTS:

Addition of tiotropium 1.25, 2.5, and 5 µg to olodaterol 5 µg increased mean trough FEV1 response by 0.054, 0.065, and 0.084 L, respectively; addition of tiotropium 1.25, 2.5, and 5 µg to olodaterol 10 µg increased mean trough FEV1 response by 0.051, 0.083, and 0.080 L, respectively. All treatments were well tolerated and incidence of adverse events was similar with all treatments.

CONCLUSIONS:

Overall, a dose response for tiotropium on top of both doses of olodaterol was observed, with increasing improvements in trough FEV1 compared to olodaterol alone as the tiotropium dose was increased.

FUNDING:

Boehringer Ingelheim.

TRIAL REGISTRATION:

ClinicalTrials.gov number, NCT01040403.

• Authors: René Aalbers, M Reza Maleki-Yazdi, Alan Hamilton, Stella Waitere-Wijker, Yihua Zhao, Valeria C Amatto, Olaf Schmidt, Leif Bjermer
• Journal: Advances in therapy (Adv Ther) Vol. 32 Issue 9 Pg. 809-22 (Sep 2015) ISSN: 1865-8652 [Electronic] United States
• PMID: 26404912 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzoxazines
• Bronchodilator Agents
• olodaterol
• Tiotropium Bromide

Topics

• Aged
• Benzoxazines (administration & dosage)
• Bronchodilator Agents (administration & dosage)
• Cross-Over Studies
• Double-Blind Method
• Female
• Forced Expiratory Volume
• Humans
• Male
• Middle Aged
• Nebulizers and Vaporizers
• Pulmonary Disease, Chronic Obstructive (drug therapy, physiopathology)
• Tiotropium Bromide (administration & dosage)
• Treatment Outcome