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

Pulmonary Disease, Chronic Obstructive Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02030535
• Other study ID #: 1237.7
• Secondary ID: 2013-002652-32
• Status: Completed
• Phase: Phase 2
• First received: January 7, 2014
• Last updated: June 19, 2015
• Start date: January 2014
• Est. completion date: June 2014

Study information

• Verified date: June 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• olodaterol
free combination with tiotropium
• tiotropium
free combination with olodaterol
• Placebo

• tiotropium
fixed dose combination with olodaterol
• olodaterol
fixed dose combination with tiotropium

Locations

Country	Name	City	State
Germany	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	1237.7.49003 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1237.7.49001 Boehringer Ingelheim Investigational Site	Weinheim

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

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