Determining Optimal Free Dose Combination of Tiotropium Bromide and BI 1744 CL in Chronic Obstructive Pulmonary Disease (COPD)

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Randomised, Double-blind, 8 Treatments, 4 Periods, Incomplete Crossover Study to Determine the Optimal Free Dose Combination of BI 1744 CL and Tiotropium Bromide (Both Delivered by the Respimat® Inhaler) After 4 Weeks Once Daily Treatment in Patients With COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01040403
• Other study ID #: 1237.18
• Secondary ID: 2009-014880-38
• Status: Completed
• Phase: Phase 2
• First received: December 28, 2009
• Last updated: June 19, 2015
• Start date: January 2010

Study information

• Verified date: June 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesNetherlands: Central Committee Research Involving Human SubjectsSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the optimum once daily dose of BI 1744 CL and tiotropium in free dose combination (delivered by the Respimat inhaler) after four week treatment in patients with COPD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion criteria:

1. All patients must sign an informed consent

2. All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) must meet the following spirometric criteria:

a post-bronchodilator forced expiratory flow in 1 second (FEV1) =<30% of predicted normal and <80% of predicted normal and a post bronchodilator FEV1 / forced vital capacity (FVC) <70% at Visit 1 4. Male or female patients, 40 years of age or older. 5. Patients must be current or ex-smokers with a smoking history of more than 10 pack years

Exclusion criteria:

• Patients with a significant disease other than COPD;

• Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;

• Patients with a history of asthma or a total blood eosinophil count >=600/mm3.

• Patients with any of the following conditions:

a diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists) a diagnosis of paroxysmal tachycardia - Patients with any of the following conditions: a history of myocardial infarction within 1 year of screening visit a diagnosis of clinically relevant cardiac arrhythmia a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years

• Patients who have undergone thoracotomy with pulmonary resection

• Patients being treated with the following concomitant medications:

medications that prolong the QT/QTc interval oral Beta-adrenergics oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day

• Pregnant or nursing women

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 (BI 1744) low
olodaterol (BI 1744) low
• low tiotropium bromide
low tiotropium bromide
• olodaterol (BI 1744) high
olodaterol (BI 1744) high
• medium tiotropium bromide
medium tiotropium bromide
• high tiotropium bromide
high tiotropium bromide
• Placebo
Placebo

Device:
• Respimat
Respimat inhaler

Locations

Country	Name	City	State
Canada	1237.18.02005 Boehringer Ingelheim Investigational Site	Grimsby	Ontario
Canada	1237.18.02001 Boehringer Ingelheim Investigational Site	Mississauga	Ontario
Canada	1237.18.02002 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1237.18.02003 Boehringer Ingelheim Investigational Site	Point Claire	Quebec
Canada	1237.18.02009 Boehringer Ingelheim Investigational Site	Quebec
Canada	1237.18.02011 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan
Canada	1237.18.02007 Boehringer Ingelheim Investigational Site	Sherbrooke	Quebec
Canada	1237.18.02008 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1237.18.02004 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Germany	1237.18.49009 Boehringer Ingelheim Investigational Site	Aschaffenburg
Germany	1237.18.49012 Boehringer Ingelheim Investigational Site	Bamberg
Germany	1237.18.49005 Boehringer Ingelheim Investigational Site	Berlin
Germany	1237.18.49004 Boehringer Ingelheim Investigational Site	Frankfurt
Germany	1237.18.49011 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1237.18.49010 Boehringer Ingelheim Investigational Site	Koblenz
Germany	1237.18.49007 Boehringer Ingelheim Investigational Site	Mannheim
Germany	1237.18.49001 Boehringer Ingelheim Investigational Site	Potsdam
Germany	1237.18.49006 Boehringer Ingelheim Investigational Site	Rodgau-Dudenhofen
Germany	1237.18.49002 Boehringer Ingelheim Investigational Site	Rüdersdorf
Germany	1237.18.49003 Boehringer Ingelheim Investigational Site	Weinheim
Germany	1237.18.49008 Boehringer Ingelheim Investigational Site	Wiesloch
Netherlands	1237.18.31004 Boehringer Ingelheim Investigational Site	Almelo
Netherlands	1237.18.31006 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1237.18.31008 Boehringer Ingelheim Investigational Site	Eindhoven
Netherlands	1237.18.31001 Boehringer Ingelheim Investigational Site	Groningen
Netherlands	1237.18.31007 Boehringer Ingelheim Investigational Site	Hengelo
Netherlands	1237.18.31005 Boehringer Ingelheim Investigational Site	Hoorn
Netherlands	1237.18.31002 Boehringer Ingelheim Investigational Site	Veldhoven
Netherlands	1237.18.31003 Boehringer Ingelheim Investigational Site	Zutphen
Sweden	1237.18.46003 Boehringer Ingelheim Investigational Site	Boden
Sweden	1237.18.46002 Boehringer Ingelheim Investigational Site	Göteborg
Sweden	1237.18.46001 Boehringer Ingelheim Investigational Site	Lund
Sweden	1237.18.46004 Boehringer Ingelheim Investigational Site	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Canada,  Germany,  Netherlands,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough FEV1 Response	Adjusted means of the trough forced expiratory volume in one second (FEV1) response (L) after four weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29	No
Secondary	Trough Forced Vital Capacity (FVC) Response	Adjusted means of trough FVC (forced vital capacity) response [L] after 4 weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29	No
Secondary	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	Adjusted means of forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-3 hour and AUC 0-6 hour responses [L] after 4 weeks treatment calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29	No
Secondary	FEV1 AUC 0-3h Response After the First Dose	Adjusted means of Forced Expiratory Volume in One Second (FEV1) Area Under Curve (AUC) 0-3h response [L] after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	No
Secondary	FEV1 Peak 0-3h Response	Adjusted means of the FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response [L] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29	No
Secondary	FEV1 Peak 0-3h Response After the First Dose	Adjusted means of the FEV1 peak 0-3h response [L] after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	No
Secondary	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	Adjusted means of the FVC AUC 0-3h and AUC 0-6h responses [L] after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29	No
Secondary	FVC AUC 0-3h Response After First Dose	Adjusted means of the FVC AUC 0-3h response [L] after first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on days 1	No
Secondary	FVC Peak 0-3h Response	Adjusted means of the FVC peak 0-3h response [L] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29	No
Secondary	FVC Peak 0-3h Response After the First Dose	Adjusted mean of the FVC peak 0-3h response [L] after the first dose. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	No
Secondary	PEF AUC 0-3h and AUC 0-6h Responses	Adjusted means of the Peak Expiratory Flow (PEF) AUC 0-3h and AUC 0-6h responses in Litres / minute (L/min) after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29	No
Secondary	PEF AUC 0-3h Response After the First Dose	Adjusted means of the Area under the curve from 0 to 3 h response in Litres / minutes of the peak expiratory flow after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	No
Secondary	PEF Peak 0-3h Response	Adjusted means of the peak expiratory flow from 0 to 3 hours (PEF peak 0-3h) response in L/min after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29	No
Secondary	PEF Peak 0-3h Response After the First Dose	Adjusted means of the Peak Expiratory flow from 0 to 3 hours response in L/min after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	No
Secondary	Individual FEV1 Measurements at Each Time Point on Day 29	Adjusted means of the FEV1 measurements [L] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29	No
Secondary	Individual FVC Measurements at Each Time Point on Day 29	Adjusted means of the FVC measurements [L] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29	No
Secondary	Individual PEF Measurements at Each Time Point on Day 29	Adjusted means of the PEF measurements [L/min] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.	Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29	No
Secondary	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Adjusted means of the weekly mean number of puffs of rescue medication during the whole day : the rescue medication was a salbutamol [albuterol] dose (100 mcg per puff).	Weeks 1 and 4	No
Secondary	Physicians Global Evaluation	Adjusted means of the Physicians Global Evaluation of the patient's respiratory condition on days 1 and 29.; The score was evaluated on a 8-points scale : Poor : 1,2; Fair : 3,4; Good : 5,6; Excellent : 7,8	Days 1 and 29	No
Secondary	Patients Global Rating	Adjusted means of the Global Rating of the patients' health (respiratory condition) on day 29.; The score was evaluated on a 7-point scale : 1 : very much better; 2 : much better; 3 : a little better; 4 : no change; 5 : a little worse; 6 : much worse; 7 : very much worse	Day 29	No
Secondary	Pulse Rate Recorded in Conjunction With Spirometry	Pulse rate recorded in conjunction with spirometry change from baseline at 30 minutes post-dose on day 29 in beats per minute (bpm).	Baseline and 30 min post-dose on day 29	No
Secondary	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic and diastolic blood pressure recorded in conjunction with spirometry change from baseline on day 29 in millimetres of mercury (mmHg).	Baseline and 30 min post-dose on day 29	No

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