A Study to Test the Combination of Tiotropium and Olodaterol Using the Respimat® Inhaler in People With Chronic Obstructive Pulmonary Disease (COPD) Who Have Different Abilities to Inhale

A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel Group Study to Compare the Efficacy of Inhaled Tiotropium + Olodaterol, Fixed Dose Combination (5 mcg/5mcg) vs. Placebo Delivered by Respimat Inhaler in Patients With Moderate to Severe COPD, Stratified by Peak Inspiratory Flow Rate [TRONARTO].

To demonstrate the efficacy of inhaled tiotropium + olodaterol via Respimat® on lung function in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) with optimal and sub-optimal Peak Inspiratory Flow Rate (PIFR). Disease severity (moderate to severe) is based on the Global Initiative for Chronic Lung Disease (GOLD) guidelines (GOLD 2 - 3)

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Tiotropium + olodaterol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10787
    • Klinische Forschung Berlin GbR
  • Frankfurt, Germany, 60596
    • IKF Pneumologie GmbH & Co. KG
  • Grosshansdorf, Germany, 22927
    • Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
  • Hamburg, Germany, 20354
    • Hamburger Institut für Therapieforschung GmbH (HIT)
  • Lübeck, Germany, 23552
    • KLB Gesundheitsforschung Lubeck GmbH
• United States
  • Alabama
    • Andalusia, Alabama, United States, 36420
      • SEC Lung
    • Jasper, Alabama, United States, 35501
      • Jasper Summit Research, LLC
  • Florida
    • Brandon, Florida, United States, 33511
      • Meris Clinical Research
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
    • Kissimmee, Florida, United States, 34746
      • Clinical Research Specialists LLC
    • Tampa, Florida, United States, 33606
      • Clinical Research of West Florida, Inc.
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Best Clinical Trials, LLC
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Infinity Medical Research
  • Michigan
    • Farmington Hills, Michigan, United States, 48152
      • Pulmonary Rsrch Inst of SE MI
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Lung Center and Sleep Institute
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Lung Center
  • New Hampshire
    • Claremont, New Hampshire, United States, 03743
      • Valley Regional Hospital
  • New York
    • Bronx, New York, United States, 10455
      • CHEAR Center LLC
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Rsrch Ctr
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Lowcountry Lung and Critical Care
    • Clinton, South Carolina, United States, 29325
      • Carolina Medical Research
    • Gaffney, South Carolina, United States, 29340
      • VitaLink Research -Gaffney
    • Spartanburg, South Carolina, United States, 29303
      • Vitalink Research - Spartansburg
  • Texas
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed and dated written informed consent in accordance with International Council on Harmonisation Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
• Male or female patients, 40 years of age or older.
• All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) >30% and <80% of predicted normal (European Coal and Steel Community (ECSC), [R94-1408]); and a postbronchodilator FEV1/ Functional Residual Capacity (FVC) <70%, at the screening visit.
• Patients must be current or ex-smokers with a smoking history of more than 10 pack years
• Patients should meet the peak inspiratory flow rate criteria (optimal or sub-optimal) at the time of randomization depending on which strata is available for inclusion in the study.
• Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

• Patients are expected to be able to perform, according to investigator's judgment, all trial related procedures including:

  • Technically acceptable pulmonary function tests (spirometry)
  • Use of In-Check DIAL G16 device to measure peak inspiratory flow rate.
  • Inhale medication in a competent manner (in the opinion of the investigator) from the Respimat® device
  • Perform technically acceptable body plethysmography measurements. This is applicable only to patients who will consent to the optional trial procedure at the selected sites.

Exclusion Criteria:

• Patients with a significant disease other than chronic obstructive pulmonary disease; a significant disease defined as a disease which, in the opinion of the investigator, and referring to the warnings to be observed as quoted in the locally applicable SmPC or prescribing information, could (i) put the patient at risk because of participation in the trial, (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.
• Patients who have had a chronic obstructive pulmonary disease exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to screening visit or during the screening period.
• Patients who experienced two or more moderate chronic obstructive pulmonary disease exacerbations (exacerbation that required treatment with antibiotics and/or oral corticosteroids), or one or more exacerbation leading to hospitalization within a year prior to visit 1.
• Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma.
• Patients taking inhaled corticosteroids (including combinations, e.g. inhaled corticosteroids / Long-Acting β2-agonist) in the 6 months prior to screening visit.
• Patients being treated with oral corticosteroid medication due to reasons other than chronic obstructive pulmonary disease exacerbation within 6 weeks prior to the screening visit.
• Patients who have completed a pulmonary rehabilitation program in the 6 weeks prior to screening visit or patients who are currently in a pulmonary rehabilitation program.
• Further criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Arm; Tiotropium + Olodaterol Fixed Dose Combination (FDC) via Respimat	Drug: Tiotropium + olodaterol; Oral Inhalation
Placebo Comparator: Placebo Arm; Matching placebo via Respimat	Drug: Placebo; Oral Inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment.	FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters. Mean is adjusted mean. A hierarchical testing procedure was used to test the primary endpoint. Each of the tests were considered confirmatory only if all previous tests were successful.	At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) After 4 Weeks of Treatment	Change from baseline in trough Forced Expiratory Volume in one second (FEV1) after 4 weeks of treatment.	At baseline and at week 4.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2020
• Primary Completion (Actual): September 7, 2020
• Study Completion (Actual): September 29, 2020

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 18, 2021
• Last Update Submitted That Met QC Criteria: October 20, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Olodaterol
• Other Study ID Numbers: 1237-0095; 2019-001719-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No