A randomised, placebo-controlled, Phase II, dose-ranging trial of once-daily treatment with olodaterol, a novel long-acting β2-agonist, for 4 weeks in patients with chronic obstructive pulmonary disease.

Abstract

BACKGROUND:

Olodaterol is a novel long-acting β2-agonist (LABA) with ≥24-h duration of action in preclinical and clinical studies.

OBJECTIVE:

This Phase II, multicentre, randomised, double-blind, placebo-controlled, parallel-group, dose-finding study evaluated four doses of once-daily olodaterol over 4 weeks in patients with chronic obstructive pulmonary disease (COPD), based on efficacy, safety and pharmacokinetic parameters.

METHODS:

Patients received olodaterol inhalation solution or placebo via Respimat® Soft Mist™ inhaler once daily for 4 weeks. Pulmonary function testing was performed pre-dose (trough) and up to 3 or 6 h post-dose, depending on visit. Primary end point was change from baseline in trough forced expiratory volume in 1 s (FEV1) after 4 weeks' treatment. Secondary end points included change from baseline in peak FEV1 and FEV1 area under the curve from 0 to 6 h.

RESULTS:

405 patients with COPD were randomised and assigned to treatment. Mean baseline post-bronchodilator FEV1 was 1.50 L (54% predicted). All olodaterol doses provided statistically significant increases in trough FEV1 compared to placebo (2 μg: 0.061 L [p = 0.0233]; 5 μg: 0.097 L [p = 0.0003]; 10 μg: 0.123 L [p < 0.0001]; 20 μg: 0.132 L [p < 0.0001]). A clear dose-response relationship was demonstrated regarding pulmonary function; the two highest olodaterol doses (10 and 20 μg) formed the plateau of the dose-response curve. All olodaterol doses were well tolerated, with no dose-dependent safety effects.

CONCLUSION:

Once-daily olodaterol demonstrated 24-h bronchodilator efficacy, confirming its potential as a once-daily LABA for the management of COPD.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT00452400.

• Authors: M Reza Maleki-Yazdi, Ekkehard Beck, Alan L Hamilton, Lawrence Korducki, Paul Koker, Charles Fogarty
• Journal: Respiratory medicine (Respir Med) Vol. 109 Issue 5 Pg. 596-605 (May 2015) ISSN: 1532-3064 [Electronic] England
• PMID: 25829298 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Adrenergic beta-2 Receptor Agonists
• Benzoxazines
• Bronchodilator Agents
• olodaterol

Topics

• Administration, Inhalation
• Adrenergic beta-2 Receptor Agonists (administration & dosage, adverse effects, pharmacokinetics)
• Aged
• Benzoxazines (administration & dosage, adverse effects, pharmacokinetics)
• Bronchodilator Agents (administration & dosage, adverse effects, pharmacokinetics)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Forced Expiratory Volume (drug effects)
• Humans
• Male
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (drug therapy, metabolism)
• Respiratory Function Tests