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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00467740
• Other study ID #: 1222.6
• Secondary ID: EUDRACT 2006-004
• Status: Completed
• Phase: Phase 2
• First received: April 30, 2007
• Last updated: June 17, 2014
• Start date: May 2007

Study information

• Verified date: June 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Therapeutic Products DirectorateFrance: Agence Française de Sécurité Sanitaire des Produits de SantéGermany: BfArM Bundesinstitut fuer Arzneimittel und MedizinprodukteUnited 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 asthma. 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: 296
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 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. Male or female patients, 18 years of age or older

3. Diagnosis of asthma (GINA)

4. Pre-bronchodilator FEV1 greater than or equal to 60% predicted and <90% predicted (ECSC);

5. Increase in FEV1 greater than or equal to 12% and 200 ml 15 minutes after 400µg salbutamol (albuterol) at Visit 1

6. Patient must have been taking Inhaled Corticosteroids for at least 12 weeks prior to screening, and must have been receiving a stable low/moderate dose for at least 6 weeks prior to screening.

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

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

Exclusion Criteria:

1. Patients with a smoking history of more than 10 pack years

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, a history of cor pulmonale, 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 have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)

6. Pregnant or nursing women

7. Women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least 2 years

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

9. Patients who are unable to comply with pulmonary medication restrictions prior to randomization

Study Design

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• BI 1744 CL

Locations

Country	Name	City	State
Canada	1222.6.017 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1222.6.011 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1222.6.003 Boehringer Ingelheim Investigational Site	Mississauga	Ontario
Canada	1222.6.008 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1222.6.015 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1222.6.013 Boehringer Ingelheim Investigational Site	Ottawa	Ontario
Canada	1222.6.004 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan
Canada	1222.6.007 Boehringer Ingelheim Investigational Site	Sherbrooke	Quebec
Canada	1222.6.002 Boehringer Ingelheim Investigational Site	Ste-Foy	Quebec
Canada	1222.6.005 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1222.6.009 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1222.6.006 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Canada	1222.6.012 Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba
Canada	1222.6.016 Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba
France	1222.6.3303A Boehringer Ingelheim Investigational Site	Bethune Cedex
France	1222.6.3308A Boehringer Ingelheim Investigational Site	Briancon
France	1222.6.3302A Boehringer Ingelheim Investigational Site	Grenoble
France	1222.6.3306A Boehringer Ingelheim Investigational Site	Lille
France	1222.6.3301A Boehringer Ingelheim Investigational Site	Montpellier
France	1222.6.3304A Boehringer Ingelheim Investigational Site	Nîmes
France	1222.6.3305A Boehringer Ingelheim Investigational Site	Saint-Pierre Cedex - La Réunion
Germany	1222.6.031 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.6.034 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.6.037 Boehringer Ingelheim Investigational Site	Gauting
Germany	1222.6.038 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1222.6.032 Boehringer Ingelheim Investigational Site	Rüdersdorf
Germany	1222.6.036 Boehringer Ingelheim Investigational Site	Wiesloch
United States	1222.6.068 National Jewish Medical Center	Denver	Colorado
United States	1222.6.072 Boehringer Ingelheim Investigational Site	Kileen	Texas
United States	1222.6.064 Arthur F. Gelb Medical Corporation, Lakewood	Lakewood	California
United States	1222.6.062 Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	1222.6.067 Northeast Medical Research Associates, Inc	North Darthmouth	Massachusetts
United States	1222.6.066 Allergy & Asthma Medical Group and Rsrch Ctr, APC	San Diego	California
United States	1222.6.069 Allergy Associates Medical Group	San Diego	California
United States	1222.6.071 Pulmonary Consultants	Tacoma	Washington
United States	1222.6.073 Boehringer Ingelheim Investigational Site	Wheat Ridge	Colorado
United States	1222.6.061 Center for Human Genomics	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough FEV1 Response After 4 Weeks	Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.	Baseline and 4 weeks	No
Secondary	Weekly Mean Pre-dose Morning PEFR After 4 Weeks	Response was defined as change from baseline. Baseline peak expiratory flow response (PEFR) was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment.	Baseline and 4 weeks	No
Secondary	Trough FEV1 Response After 1 Week	Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.	Baseline and 1 week	No
Secondary	Trough FEV1 Response After 2 Weeks	Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation at the end of the dosing interval.	Baseline and 2 weeks	No
Secondary	Trough FVC Response After 1 Week	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.	Baseline and 1 week	No
Secondary	Trough FVC Response After 2 Weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.	Baseline and 2 weeks	No
Secondary	Trough FVC Response After 4 Weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation at the end of the dosing interval.	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. 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	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. 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	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. 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 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. 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. 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	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) 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. 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 4	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.	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 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. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after 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 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.	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	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.	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	Peak FVC (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 FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after 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 1 weeks	No
Secondary	Peak FVC (0-3h) Response After 1 Week	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after 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 1 weeks	No
Secondary	Peak FVC (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 FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after 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 2 weeks	No
Secondary	Peak FVC (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 FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after 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 6-12 h (AUC 6-12h) 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. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.	1 hour (h) prior to dose on first day of randomized treatment (baseline) and 1h, 3h, 6h, 9h, 12h relative to dose at Week 4	No
Secondary	Weekly Mean Evening PEFR After 4 Weeks	Response was defined as change from baseline. Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment.	Baseline and 4 weeks	No
Secondary	PEFR Variability After 4 Weeks	PEFR variability represents the absolute difference between the highest morning PEFR value and the highest evening PEFR value of 1 day, divided by the arithmetic mean of these 2 PEFR values and expressed as a percent, weekly means.	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]) as assessed by the e-Diary (e-Diary incorporated in AM2+).	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 (a metabolite of olodaterol) in plasma from 0 to time t=3	30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration	No
Secondary	Maximum Concentration (Cmax)	Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.	30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration	No
Secondary	Time From Dosing to the Maximum Concentration (Tmax)	tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.	30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration	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 (a metabolite of olodaterol) in plasma from 0 to time t=3 at steady state.	30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration	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 (a metabolite of olodaterol) in plasma from 0 to time t=6 at steady state.	30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration	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 (a metabolite of olodaterol) in plasma from 0 to time t=24 at steady state.	30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration	No
Secondary	Maximum Concentration at Steady State (Cmax,ss)	Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state.	30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration	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 (a metabolite of olodaterol) in plasma at steady state.	30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration	No
Secondary	Total Score in Asthma Control Questionnaire After 4 Weeks	Adequacy of asthma control was assessed using a scale of: 0=totally controlled, to 6=Severely uncontrolled.	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 29 days	No

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