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

Phase 2CompletedNCT02030535

Boehringer Ingelheim53 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

olodaterolDRUG

free combination with tiotropium

tiotropiumDRUG

free combination with olodaterol

PlaceboDRUG

tiotropiumDRUG

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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

Locations (6)

1237.7.49004 Boehringer Ingelheim Investigational Site

Berlin, Germany

1237.7.49005 Boehringer Ingelheim Investigational Site

Berlin, Germany

1237.7.49007 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

1237.7.49002 Boehringer Ingelheim Investigational Site

Großhansdorf, Germany

Outcomes

Primary Outcomes

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.

Time frame: 1 hour (h) and 10 min pre-dose and at 15 min, 30 min, 1 h, 2 h and 3 h post-dose

Secondary Outcomes

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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Data from ClinicalTrials.gov

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fixed dose combination with olodaterol

olodaterolDRUG

fixed dose combination with tiotropium

1237.7.49003 Boehringer Ingelheim Investigational Site

Hamburg, Germany

1237.7.49001 Boehringer Ingelheim Investigational Site

Weinheim, Germany

Heart Rate Change From Patient Baseline at Individual Post-dose Time Points

Heart rate change from patient baseline at individual post-dose time points

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose