Clinical trial NCT02030535: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-01-08
Enrollment: 53
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3hours) Response After Single-dose Administration
timeFrame: 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:
measure: Mean (Heart Rate Corrected QT Interval (Using Fredericia Adjustment)) QTcF Interval Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Peak QTcF Interval Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Mean Heart Rate Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Peak Heart Rate Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Heart Rate Change From Patient Baseline at Individual Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Mean RR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Peak RR Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: RR Change From Patient Baseline at Individual Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Mean QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Peak QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: QT Change From Patient Baseline at Individual Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Mean QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Peak QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: QTcB Change From Patient Baseline at Individual Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Mean PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Peak PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: PR Change From Patient Baseline at Individual Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Mean QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: Peak QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
measure: QRS Change From Patient Baseline at Individual Post-dose Time Points
timeFrame: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: 1237.7.49004 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1237.7.49005 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1237.7.49007 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 1237.7.49002 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1237.7.49003 Boehringer Ingelheim Investigational Site
city: Weinheim
country: Germany
facility: 1237.7.49001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: