Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Patients With COPD.

Asthma Clinical Trial

Official title:

Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Treatment of Orally Inhaled BI 1744 CL (3 - 4 Doses) Delivered by the Respimat® Inhaler in Patients With COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00452400
• Other study ID #: 1222.5
• Status: Completed
• Phase: Phase 2
• First received: March 26, 2007
• Last updated: June 17, 2014
• Start date: March 2007

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Therapeutic Products DirectorateGermany: BfArM Bundesinstitut fuer Arzneimittel und MedizinprodukteNetherlands: Central Committee on Research Involving Human Subjects (CCMO)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL inhalation solution delivered by the Respimat® inhaler for four weeks in patients with chronic obstructive pulmonary disease (COPD). The selection of the optimum dose(s) will be based on bronchodilator efficacy (how well it helps your breathing), safety evaluations and pharmacokinetic evaluations (the amount of the medication found in your blood).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 409
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions

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

Patients must have relatively stable, moderate to severe airway obstruction with a post-bronchodilator FEV1  30% of predicted normal and < 80% of predicted normal and a post-bronchodilator FEV1 / FVC < 70% at Visit 1

3. Male or female patients, 40 years of age or older

4. 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

5. Patients must be able to perform technically acceptable pulmonary function tests and PEFR measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol

6. Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler (MDI).

Exclusion Criteria:

Selection of relevant exclusion criteria:

1. Patients with a history of asthma or a total blood eosinophil count 600/mm3.

2. Patients with any of the following conditions:

• a diagnosis of thyrotoxicosis

• a diagnosis of paroxysmal tachycardia (>100 beats per minute)

• a marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms).

• a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)

3. Patients with any of the following conditions:

• a history of myocardial infarction within 1 year of screening visit (Visit 1)

• a diagnosis of clinically relevant cardiac arrhythmia

• known active tuberculosis

• a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed)

• a history of life-threatening pulmonary obstruction

• a history of cystic fibrosis

• clinically evident bronchiectasis

• a history of significant alcohol or drug abuse

4. Patients who have undergone thoracotomy with pulmonary resection

5. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits

6. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the Screening Visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program

7. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)

8. Pregnant or nursing women

9. Women of childbearing potential not using a highly effective method of birth control

10. Patients who have previously been randomized in this study or are currently participating in another study

11. Patients who are unable to comply with medication restrictions.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Chronic Disease
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• BI 1744CL

Locations

Country	Name	City	State
Canada	1222.5.038 Courtice Health Centre	Courtice	Ontario
Canada	1222.5.032 Division of Respirology	Halifax	Nova Scotia
Canada	1222.5.037 Kingston General Hospital	Kingston	Ontario
Canada	1222.5.031 Alpha Medical Research Inc.	Mississauga	Ontario
Canada	1222.5.036 Department of Respiratory Medicine	Saskatoon	Saskatchewan
Canada	1222.5.033 Centre de Recherche Clinique -CHUS	Sherbrooke	Quebec
Canada	1222.5.035 Hopital Laval	Ste-Foy	Quebec
Canada	1222.5.034 Pulmonary Care Clinic and Research Centre	Toronto	Ontario
Canada	1222.5.040 Respiratory Research Lab	Toronto	Ontario
Canada	1222.5.039 St. Boniface General Hospital & Health Science Centre	Winnipeg	Manitoba
Germany	1222.5.046 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.5.049 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.5.052 Boehringer Ingelheim Investigational Site	Gauting
Germany	1222.5.051 Boehringer Ingelheim Investigational Site	Großhansdorf
Germany	1222.5.047 Boehringer Ingelheim Investigational Site	Rüdersdorf
Germany	1222.5.048 Boehringer Ingelheim Investigational Site	Wiesbaden
Netherlands	1222.5.058 Boehringer Ingelheim Investigational Site	Almelo
Netherlands	1222.5.056 Boehringer Ingelheim Investigational Site	Breda
Netherlands	1222.5.059 Boehringer Ingelheim Investigational Site	Eindhoven
Netherlands	1222.5.057 Boehringer Ingelheim Investigational Site	Heerlen
United States	1222.5.03 Boehringer Ingelheim Investigational Site	Birmingham	Alabama
United States	1222.5.08 Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	1222.5.19 Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	1222.5.04 Boehringer Ingelheim Investigational Site	Coeur D'Alene	Idaho
United States	1222.5.14 Boehringer Ingelheim Investigational Site	Denver	Colorado
United States	1222.5.05 Boehringer Ingelheim Investigational Site	Hershey	Pennsylvania
United States	1222.5.21 Boehringer Ingelheim Investigational Site	Kileen	Texas
United States	1222.5.07 Boehringer Ingelheim Investigational Site	Lakewood	California
United States	1222.5.10 Boehringer Ingelheim Investigational Site	Medford	Oregon
United States	1222.5.24 Boehringer Ingelheim Investigational Site	New York	New York
United States	1222.5.15 Boehringer Ingelheim Investigational Site	Panama City	Florida
United States	1222.5.02 Boehringer Ingelheim Investigational Site	Philadelphia	Pennsylvania
United States	1222.5.12 Boehringer Ingelheim Investigational Site	Raleigh	North Carolina
United States	1222.5.11 Boehringer Ingelheim Investigational Site	Reno	Nevada
United States	1222.5.23 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	1222.5.01 Boehringer Ingelheim Investigational Site	San Antonio	Texas
United States	1222.5.22 Boehringer Ingelheim Investigational Site	Shreveport	Louisiana
United States	1222.5.06 Boehringer Ingelheim Investigational Site	Spartanburg	South Carolina
United States	1222.5.18 Boehringer Ingelheim Investigational Site	Stamford	Connecticut
United States	1222.5.20 Boehringer Ingelheim Investigational Site	Tacoma	Washington
United States	1222.5.17 Boehringer Ingelheim Investigational Site	Wheat Ridge	Colorado
United States	1222.5.13 Boehringer Ingelheim Investigational Site	WheatRidge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough FEV1 Response After 4 Weeks	Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.	Baseline and 4 weeks	No
Secondary	Trough FEV1 Response After 1 Week	Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.	Baseline and 1 week	No
Secondary	Trough FEV1 Response After 2 Weeks	Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.	Baseline and 2 weeks	No
Secondary	Trough FVC Response After 1 Week	Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.	Baseline and 1 week	No
Secondary	Trough FVC Response After 2 Weeks	Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.	Baseline and 2 weeks	No
Secondary	Trough FVC Response After 4 Weeks	Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.	Baseline and 4 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4	No
Secondary	Peak FEV1 (0-3h) Response After 4 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks	No
Secondary	Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4	No
Secondary	Peak FVC (0-3h) Response After 4 Weeks	Peak (0-3h) will be the maximum post-dose value during the first 3 hours. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours postdose using the trapezoidal rule, divided by the observation time (3h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at day 1	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2	No
Secondary	Peak FEV1 (0-3h) Response At Day 1	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.Means are adjusted using a mixed effects model with baseline,treatment and centre (centre random, all other effects fixed).	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose at day 1	No
Secondary	Peak FEV1 (0-3h) Response After 1 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 week	No
Secondary	Peak FEV1 (0-3h) Response After 2 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	baseline and day1	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	Baseline and 1 week	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	Baseline and 2 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	Baseline and 4 weeks	No
Secondary	Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks	Baseline PEFR was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment.	4 weeks	No
Secondary	Weekly Mean Evening PEFR After 4 Weeks	Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment.	4 weeks	No
Secondary	Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks	Weekly mean number of occasions of rescue therapy used per day (PRN salbutamol (albuterol))	4 weeks	No
Secondary	Area Under Curve From 0 to 3 Hours (AUC0-3)	AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3.	Baseline and 4 weeks	No
Secondary	Maximum Concentration (Cmax)	Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma.	Baseline and 4 weeks	No
Secondary	Time From Dosing to the Maximum Concentration (Tmax)	tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma.	Baseline and 4 weeks	No
Secondary	Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)	AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3 at steady state.	Baseline and 4 weeks	No
Secondary	Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)	AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=6 at steady state.	Baseline and 4 weeks	No
Secondary	Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)	AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=24 at steady state.	Baseline and 4 weeks	No
Secondary	Maximum Concentration at Steady State (Cmax,ss)	Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.	Baseline and 4 weeks	No
Secondary	Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)	tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.	Baseline and 4 weeks	No
Secondary	Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination	Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events.	4 weeks	No
Secondary	Laboratory Testing: Average Change From Baseline of Potassium	Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value.	Baseline and day 29	No