Efficacy and Safety of 4 Weeks of Treatment With Inhaled BI 1744 CL in Patients With Asthma
- Conditions
- Asthma
- Registration Number
- NCT00467740
- Lead Sponsor
- Boehringer Ingelheim
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 296
- All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions
- Male or female patients, 18 years of age or older
- Diagnosis of asthma (GINA)
- Pre-bronchodilator FEV1 greater than or equal to 60% predicted and <90% predicted (ECSC);
- Increase in FEV1 greater than or equal to 12% and 200 ml 15 minutes after 400µg salbutamol (albuterol) at Visit 1
- 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.
- 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
- Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler (MDI).
- Patients with a smoking history of more than 10 pack years
- 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)
- 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
- Patients who have undergone thoracotomy with pulmonary resection
- Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)
- Pregnant or nursing women
- 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
- Patients 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Trough FEV1 Response After 4 Weeks Baseline and 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.
- Secondary Outcome Measures
Name Time Method Weekly Mean Pre-dose Morning PEFR After 4 Weeks Baseline and 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.
Trough FEV1 Response After 1 Week Baseline and 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.
Trough FEV1 Response After 2 Weeks Baseline and 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.
Trough FVC Response After 1 Week Baseline and 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.
Trough FVC Response After 2 Weeks Baseline and 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.
Trough FVC Response After 4 Weeks Baseline and 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.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 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 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.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1 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 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.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4 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 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.
Peak FEV1 (0-3h) Response At Day 1 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 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.
Peak FEV1 (0-3h) Response After 1 Week 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 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.
Peak FEV1 (0-3h) Response After 2 Weeks 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 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.
Peak FEV1 (0-3h) Response After 4 Weeks 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 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.
Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4 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 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.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1 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 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.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2 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 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.
Peak FVC (0-3h) Response At Day 1 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 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.
Peak FVC (0-3h) Response After 1 Week 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 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.
Peak FVC (0-3h) Response After 2 Weeks 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 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.
Peak FVC (0-3h) Response After 4 Weeks 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 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.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4 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 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.
Weekly Mean Evening PEFR After 4 Weeks Baseline and 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.
PEFR Variability After 4 Weeks 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.
Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks 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+).
Area Under Curve From 0 to 3 Hours (AUC0-3) 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration 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
Maximum Concentration (Cmax) 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.
Time From Dosing to the Maximum Concentration (Tmax) 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma.
Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss) 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration 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.
Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss) 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration 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.
Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss) 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration 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.
Maximum Concentration at Steady State (Cmax,ss) 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state.
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state.
Total Score in Asthma Control Questionnaire After 4 Weeks 4 weeks Adequacy of asthma control was assessed using a scale of: 0=totally controlled, to 6=Severely uncontrolled.
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination 4 weeks Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events.
Laboratory Testing: Average Change From Baseline of Potassium Baseline and 29 days Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value.
Trial Locations
- Locations (37)
1222.6.004 Boehringer Ingelheim Investigational Site
🇨🇦Saskatoon, Saskatchewan, Canada
1222.6.006 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
1222.6.073 Boehringer Ingelheim Investigational Site
🇺🇸Wheat Ridge, Colorado, 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
1222.6.067 Northeast Medical Research Associates, Inc
🇺🇸North Darthmouth, Massachusetts, United States
1222.6.068 National Jewish Medical Center
🇺🇸Denver, Colorado, United States
1222.6.072 Boehringer Ingelheim Investigational Site
🇺🇸Kileen, Texas, United States
1222.6.038 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1222.6.016 Boehringer Ingelheim Investigational Site
🇨🇦Winnipeg, Manitoba, Canada
1222.6.011 Boehringer Ingelheim Investigational Site
🇨🇦Hamilton, Ontario, Canada
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
1222.6.3301A 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, France
1222.6.032 Boehringer Ingelheim Investigational Site
🇩🇪Rüdersdorf, Germany
1222.6.031 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.6.036 Boehringer Ingelheim Investigational Site
🇩🇪Wiesloch, Germany
1222.6.062 Boehringer Ingelheim Investigational Site
🇺🇸Los Angeles, California, United States
1222.6.064 Arthur F. Gelb Medical Corporation, Lakewood
🇺🇸Lakewood, California, United States
1222.6.017 Boehringer Ingelheim Investigational Site
🇨🇦Calgary, Alberta, Canada
1222.6.071 Pulmonary Consultants
🇺🇸Tacoma, Washington, United States
1222.6.012 Boehringer Ingelheim Investigational Site
🇨🇦Winnipeg, Manitoba, Canada
1222.6.003 Boehringer Ingelheim Investigational Site
🇨🇦Mississauga, Ontario, Canada
1222.6.009 Boehringer Ingelheim Investigational Site
🇨🇦Toronto, Ontario, Canada
1222.6.007 Boehringer Ingelheim Investigational Site
🇨🇦Sherbrooke, Quebec, Canada
1222.6.008 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
1222.6.015 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
1222.6.002 Boehringer Ingelheim Investigational Site
🇨🇦Ste-Foy, Quebec, Canada
1222.6.3306A Boehringer Ingelheim Investigational Site
🇫🇷Lille, France
1222.6.034 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.6.037 Boehringer Ingelheim Investigational Site
🇩🇪Gauting, Germany
1222.6.005 Boehringer Ingelheim Investigational Site
🇨🇦Toronto, Ontario, Canada
1222.6.013 Boehringer Ingelheim Investigational Site
🇨🇦Ottawa, Ontario, Canada
1222.6.061 Center for Human Genomics
🇺🇸Winston-Salem, North Carolina, United States