Study to Evaluate the Effect on Lung Function and ECG When a Combination of Tiotropium Plus Olodaterol is Administered to Patients With COPD Either From a Single Inhaler or Each Compound is Administered After Each Other From Two Different Inhalers

A Randomised, Placebo-controlled, Double-blind, Single Dose, Cross-over Study to Evaluate the Efficacy and Safety of Orally Inhaled Tiotropium + Olodaterol as Both a Fixed Dose Combination and a Free Combination (Both Delivered by the Respimat® Inhaler) in Patients With Chronic Obstructive Pulmonary Disease (COPD)

The primary objective of this study is to evaluate the efficacy and safety of orally inhaled tiotropium and olodaterol as both a fixed dose combination and a free combination with respect to lung function and ECG parameters

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • 1237.7.49004 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1237.7.49005 Boehringer Ingelheim Investigational Site
  • Frankfurt, Germany
    • 1237.7.49007 Boehringer Ingelheim Investigational Site
  • Großhansdorf, Germany
    • 1237.7.49002 Boehringer Ingelheim Investigational Site
  • Hamburg, Germany
    • 1237.7.49003 Boehringer Ingelheim Investigational Site
  • Weinheim, Germany
    • 1237.7.49001 Boehringer Ingelheim Investigational Site

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:

• patients must sign informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.
• Patients must have a diagnosis of COPD and must meet the following spirometric criteria:

Patients must have relatively stable airway obstruction with a post-bronchodilator (10 to 45 minutes after 400mcg salbutamol) FEV1>30% and < 80% of predicted normal (ECSC, GOLD II - III) and a post-bronchodilator FEV1/FVC <70% at Visit 1

• Male or female patients, 40 years of age or older.
• Patients must be current or ex-smokers with a smoking history of more than 10 pack years.
• Patients who have never smoked cigarettes must be excluded.
• Patients must be able to perform technically acceptable pulmonary function tests according to ATS/ERS guidelines and maintain records in a paper diary
• Patients must be able to inhale medication in a competent manner from the RESPIMAT inhaler and from a metered dose inhaler (MDI).

Exclusion criteria:

• Significant disease other than COPD
• Clinically relevant abnormal lab values.
• History of asthma.
• Diagnosis of thyrotoxicosis
• Diagnosis of paroxysmal tachycardia
• History of myocardial infarction within 1 year of screening visit
• Unstable or life-threatening cardiac arrhythmia
• Hospitalization for heart failure within the past year
• Known active tuberculosis
• Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
• History of life-threatening pulmonary obstruction and patients with chronic respiratory failure
• History of cystic fibrosis
• Clinically evident bronchiectasis
• History of significant alcohol or drug abuse
• Thoracotomy with pulmonary resection
• Patients treated with oral or patch ß-adrenergics
• Patients treated with oral corticosteroid medication at unstable doses or at doses in excess of 10mg prednisolone per day or equivalent
• Regular use of daytime oxygen therapy for more than one hour per day
• Pulmonary rehabilitation program in the six weeks prior to the screening visit or patients currently in a pulmonary rehabilitation program
• Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
• Known hypersensitivity to ß-adrenergic and/or anticholinergic drugs, BAC, EDTA
• Pregnant or nursing women
• Women of childbearing potential not using a highly effective method of birth control
• Patient who have previously been randomized in this study or are currently participating in another study
• Patients who are unable to comply with pulmonary medication restrictions prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tiotropium/Olodaterol FDC; patient will receive tiotropium and olodaterol in a fixed dose combination	Drug: olodaterol; free combination with tiotropium; Drug: tiotropium; free combination with olodaterol; Drug: tiotropium; fixed dose combination with olodaterol; Drug: olodaterol; fixed dose combination with tiotropium
EXPERIMENTAL: Tiotropium and Olodaterol FC; patient will receive tiotropium and olodaterol in a free combination	Drug: olodaterol; free combination with tiotropium; Drug: tiotropium; free combination with olodaterol; Drug: tiotropium; fixed dose combination with olodaterol; Drug: olodaterol; fixed dose combination with tiotropium
PLACEBO_COMPARATOR: Placebo; patient will receive placebo	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3hours) Response After Single-dose Administration	The response was defined as the change from patient baseline. Patient baseline was the average of the mean pre-dose values (period baseline) on each test day (Visit 2 (Day 1), Visit 3 (Day 22 (±7days)), and Visit 4 (Day 43±7days)). For patients who did not complete all periods, patient baseline was the average of the available period baselines. The means presented are the adjusted means.	1 hour (h) and 10 min pre-dose and at 15 min, 30 min, 1 h, 2 h and 3 h post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean (Heart Rate Corrected QT Interval (Using Fredericia Adjustment)) QTcF Interval Change From Patient Baseline Over All Post-dose Time Points	Mean QTcF interval change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Peak QTcF Interval Change From Patient Baseline Over All Post-dose Time Points	Peak QTcF interval change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Mean Heart Rate Change From Patient Baseline Over All Post-dose Time Points	Mean heart rate change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Peak Heart Rate Change From Patient Baseline Over All Post-dose Time Points	Peak heart rate change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Heart Rate Change From Patient Baseline at Individual Post-dose Time Points	Heart rate change from patient baseline at individual post-dose time points	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Mean RR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points	Mean RR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Peak RR Change From Patient Baseline Over All Post-dose Time Points	Peak RR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
RR Change From Patient Baseline at Individual Post-dose Time Points	RR change from patient baseline at individual post-dose time points	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Mean QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points	Mean QT change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Peak QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points	Peak QT change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
QT Change From Patient Baseline at Individual Post-dose Time Points	QT change from patient baseline at individual post-dose time points	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Mean QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points	Mean QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment))change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Peak QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points	Peak QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment))change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
QTcB Change From Patient Baseline at Individual Post-dose Time Points	QTcB change from patient baseline at individual post-dose time points	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Mean PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points	Mean PR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Peak PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points	Peak PR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
PR Change From Patient Baseline at Individual Post-dose Time Points	PR change from patient baseline at individual post-dose time points	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Mean QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points	Mean QRS change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Peak QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points	Peak QRS change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min)	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
QRS Change From Patient Baseline at Individual Post-dose Time Points	QRS change from patient baseline at individual post-dose time points	40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: January 7, 2014
• First Submitted That Met QC Criteria: January 7, 2014
• First Posted (ESTIMATE): January 8, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 16, 2015
• Last Update Submitted That Met QC Criteria: June 19, 2015
• Last Verified: June 1, 2015

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: 1237.7; 2013-002652-32 (EUDRACT_NUMBER: EudraCT)