A Study of the Safety and Efficacy of 4 Doses of BI 1744 CL Delivered Via the Respimat in Patients With Asthma.
- Conditions
- Asthma
- Interventions
- Registration Number
- NCT01013753
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study is to determine the efficacy and safety of 4 doses of BI 1744 CL inhalation solution delivered by the Respimat® inhaler once daily for four weeks in patients with asthma in comparison to placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 198
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Olodaterol (BI 1744) low Olodaterol (BI 1744) low Low dose inhaled orally once daily from the Respimat inhaler Olodaterol (BI 1744) high Olodaterol (BI 1744) high High dose inhaled orally once daily from the Respimat inhaler Olodaterol (BI 1744) medium Olodaterol (BI 1744) medium Medium dose inhaled orally once daily from the Respimat inhaler Formoterol 12 mcg Formoterol 12 mcg 12mcg inhaled twice daily from the Aerolizer inhaler Olodaterol (BI 1744) very low Olodaterol (BI 1744) very low Very low dose inhaled orally once daily from the Respimat inhaler Placebo Placebo Olodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler
- Primary Outcome Measures
Name Time Method Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening 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 at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.
- Secondary Outcome Measures
Name Time Method FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response at the End of Each Treatment Period 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min related to evening 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 at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response at the End of Each Treatment Period 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening 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 at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Peak FEV1 Within 24 Hours Post-dose Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening 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 at the randomisation visit. Peak FEV1 within 24 hours post dose measured following the evening trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Trough FEV1 Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening 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 at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h , 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Peak FVC Within 24 Hours Post-dose Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC within 24 hours post dose measured following the trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Trough FVC Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds.
FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 min, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
PEF Daily Variability 2-4 weeks PEF daily variability was assessed by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). PEF daily variability is the absolute difference between the morning and the evening PEF value divided by the mean of these two values, expressed as a percent. Means are adjusted for treatment, period, patient and study baseline.
Peak PEF Within 24 Hours Post-dose Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Peak PEF within 24 hours post-dose measured following the evening trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Trough PEF Response 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Mean Pre-dose Morning PEF (PEF a.m.) 2-4 weeks PEF a.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Mean Pre-dose Evening PEF (PEF p.m.) 2-4 weeks PEF p.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Mean Pre-dose Morning FEV1 (FEV1 a.m.) 2-4 weeks FEV1 a.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Mean Pre-dose Evening FEV1 (FEV1 p.m.) 2-4 weeks FEV1 p.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Mean Number of Puffs of Rescue Medication During the Whole Day 2-4 weeks Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline.
Percentage of Asthma Symptom Free Days 2-4 weeks Percentage of asthma-symptom free days after the first 2 weeks of each treatment period was calculated as the number of symptom-free days divided by the number of days on treatment multiplied by 100. A symptom-free day was defined as a day in which no asthma symptoms were recorded, no rescue medication was recorded, activities during the day were not at all limited due to asthma, no shortness of breath during the day was recorded, no wheezing or coughing during the day and no night-time awakenings due to asthma were recorded. Assessed by patients at home using the AM2+ device.
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) 2-4 weeks Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment.
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) 2-4 weeks Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment.
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) 2-4 weeks Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment.
Total Asthma Quality of Life Questionnaire (AQLQ(s)) Score 4 weeks Total score from the Standardised Asthma Quality of Life Questionnaire (AQLQ (s)) at the end of each 4 week treatment period. The AQLQ(s) contains 32 questions, each question has a 7 point scale from 1 (highest intensity) till 7 (no symptoms). Total score was defined as the sum of all items divided by the number of items.
Total Asthma Control Questionnaire (ACQ) Score 4 weeks Control of asthma as assessed by the ACQ at the end of each 4-week treatment period.The ACQ contains 7 questions, each question has a 7 point scale from 0 (no symptoms) till 6 (highest intensity). Total score was defined as the sum of all items divided by the number of items.
Potassium 1 Hour Pre-dose 4 weeks Effect on potassium evaluated 1 hour pre-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale.
Potassium 1 Hour Post-dose 4 weeks Effect on potassium evaluated 1 hour post-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale.
Potassium 3 Hours Post-dose 4 weeks Effect on potassium evaluated 3 hours post-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale.
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG 4 weeks Clinical relevant abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.
Trial Locations
- Locations (27)
1222.27.43004 Boehringer Ingelheim Investigational Site
🇦🇹Schlüsslberg, Austria
1222.27.48001 Boehringer Ingelheim Investigational Site
🇵🇱Lodz, Poland
1222.27.48004 Boehringer Ingelheim Investigational Site
🇵🇱Proszowice, Poland
1222.27.40002 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
1222.27.40003 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
1222.27.42101 Boehringer Ingelheim Investigational Site
🇸🇰Bardejov, Slovakia
1222.27.42103 Boehringer Ingelheim Investigational Site
🇸🇰Lucenec, Slovakia
1222.27.42104 Boehringer Ingelheim Investigational Site
🇸🇰Martin, Slovakia
1222.27.42102 Boehringer Ingelheim Investigational Site
🇸🇰Spisska Nova Ves, Slovakia
1222.27.38601 Boehringer Ingelheim Investigational Site
🇸🇮Golnik, Slovenia
1222.27.38603 Boehringer Ingelheim Investigational Site
🇸🇮Hoce, Slovenia
1222.27.38605 Boehringer Ingelheim Investigational Site
🇸🇮Kamnik, Slovenia
1222.27.38604 Boehringer Ingelheim Investigational Site
🇸🇮Topolsica, Slovenia
1222.27.49002 Boehringer Ingelheim Investigational Site
🇩🇪Lübeck, Germany
1222.27.49010 Boehringer Ingelheim Investigational Site
🇩🇪Wiesloch, Germany
1222.27.43002 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
1222.27.43003 Boehringer Ingelheim Investigational Site
🇦🇹Wien, Austria
1222.27.49004 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.27.43001 Boehringer Ingelheim Investigational Site
🇦🇹Thalheim bei Wels, Austria
1222.27.49003 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.27.49009 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.27.49011 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt, Germany
1222.27.48002 Boehringer Ingelheim Investigational Site
🇵🇱Lodz, Poland
1222.27.48003 Boehringer Ingelheim Investigational Site
🇵🇱Poznan, Poland
1222.27.49008 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany
1222.27.49007 Boehringer Ingelheim Investigational Site
🇩🇪Rüdersdorf, Germany
1222.27.49006 Boehringer Ingelheim Investigational Site
🇩🇪Wiesbaden, Germany