A Study to Compare the Efficacy and Safety of Different Dosings of Olodaterol Administered With the Respimat® Inhaler in Patients With Moderate to Severe Asthma
- Conditions
- Asthma
- Interventions
- Registration Number
- NCT01311661
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
This study will compare efficacy and safety of different regimens of olodaterol administration in asthma (once daily, twice daily) with placebo in a complete cross-over design each within one of the two daily dose groups (medium or high daily dose).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 206
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Olodaterol medium daily dose Olodaterol low daily dose twice daily Olodaterol medium daily dose given either as once daily or split into two low doses daily or placebo only in randomised sequence of three cross-over treatment phases Olodaterol medium daily dose Placebo twice daily Olodaterol medium daily dose given either as once daily or split into two low doses daily or placebo only in randomised sequence of three cross-over treatment phases Olodaterol high daily dose Placebo twice daily Olodaterol high daily dose given either as once daily or split into two medium doses daily or placebo only in randomised sequence of three cross-over treatment phases Olodaterol high daily dose Olodaterol medium daily dose twice daily Olodaterol high daily dose given either as once daily or split into two medium doses daily or placebo only in randomised sequence of three cross-over treatment phases Olodaterol high daily dose Olodaterol high daily dose once daily and placebo Olodaterol high daily dose given either as once daily or split into two medium doses daily or placebo only in randomised sequence of three cross-over treatment phases Olodaterol medium daily dose Olodaterol medium daily dose once daily and placebo Olodaterol medium daily dose given either as once daily or split into two low doses daily or placebo only in randomised sequence of three cross-over treatment phases
- 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, 6 h, 8 h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 Hours (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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 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 Hours (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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 morning trial drug inhalation at the end of each 3 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 morning dose after 3 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 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 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.
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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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.
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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 morning trial drug inhalation at the end of each 3 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 morning dose after 3 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 FVC values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 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, 6 h, 8h, 10 h, 11 h 50 min related to morning dose after 3 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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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.
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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 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 morning trial drug inhalation at the end of each 3 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 morning dose after 3 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 PEF values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline.
Mean Pre-dose Morning PEF (PEF a.m.) 0-3 weeks PEF a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Mean Pre-dose Evening PEF (PEF p.m.) 0-3 weeks PEF p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
PEF Daily Variability 0-3 weeks PEF daily variability was assessed by patients at home using the AM3 device (overall means obtained during each period of randomised treatment 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.
Mean Pre-dose Morning FEV1 (FEV1 a.m.) 0-3 weeks FEV1 a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Mean Pre-dose Evening FEV1 (FEV1 p.m.) 0-3 weeks FEV1 p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Mean Number of Puffs of Rescue Medication During the Whole Day 0-3 weeks Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM3 device (overall mean number obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline.
Percentage of Asthma Symptom Free Days 0-3 weeks Percentage of asthma-symptom free days 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 AM3 device.
Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall) 0-3 weeks Assessed by patients at home using the AM3 device during each period of randomised treatment.
Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall) 0-3 weeks Assessed by patients at home using the AM3 device during each period of randomised treatment .
Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall) 0-3 weeks Assessed by patients at home using the AM3 device during each period of randomised treatment.
Total Asthma Control Questionnaire (ACQ) Score 3 weeks Control of asthma as assessed by the ACQ at the end of each 3-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.
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG 3 weeks + 12 days 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. Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period.
Trial Locations
- Locations (36)
1222.29.49006 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.29.11012 Boehringer Ingelheim Investigational Site
🇺🇸Wheat Ridge, Colorado, United States
1222.29.36003 Boehringer Ingelheim Investigational Site
🇭🇺Nyiregyhaza, Hungary
1222.29.11003 Boehringer Ingelheim Investigational Site
🇺🇸Raleigh, North Carolina, United States
1222.29.11008 Boehringer Ingelheim Investigational Site
🇺🇸Canton, Ohio, United States
1222.29.11001 Boehringer Ingelheim Investigational Site
🇺🇸Centennial, Colorado, United States
1222.29.11002 Boehringer Ingelheim Investigational Site
🇺🇸Overland Park, Kansas, United States
1222.29.11005 Boehringer Ingelheim Investigational Site
🇺🇸Spartanburg, South Carolina, United States
1222.29.49002 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt, Germany
1222.29.11004 Boehringer Ingelheim Investigational Site
🇺🇸North Dartmouth, Massachusetts, United States
1222.29.11010 Boehringer Ingelheim Investigational Site
🇺🇸Richmond, Virginia, United States
1222.29.49010 Boehringer Ingelheim Investigational Site
🇩🇪Großhansdorf, Germany
1222.29.36002 Boehringer Ingelheim Investigational Site
🇭🇺Mosonmagyarovar, Hungary
1222.29.36001 Boehringer Ingelheim Investigational Site
🇭🇺Sopron, Hungary
1222.29.43003 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
1222.29.43001 Boehringer Ingelheim Investigational Site
🇦🇹Thalheim bei Wels, Austria
1222.29.43004 Boehringer Ingelheim Investigational Site
🇦🇹Wels, Austria
1222.29.38002 Boehringer Ingelheim Investigational Site
🇸🇮Kamnik, Slovenia
1222.29.49008 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.29.49003 Boehringer Ingelheim Investigational Site
🇩🇪Lübeck, Germany
1222.29.49005 Boehringer Ingelheim Investigational Site
🇩🇪Rüdersdorf, Germany
1222.29.49001 Boehringer Ingelheim Investigational Site
🇩🇪Wiesbaden, Germany
1222.29.49009 Boehringer Ingelheim Investigational Site
🇩🇪Wiesloch, Germany
1222.29.11011 Boehringer Ingelheim Investigational Site
🇺🇸St. Louis, Missouri, United States
1222.29.11006 Boehringer Ingelheim Investigational Site
🇺🇸Huntington Beach, California, United States
1222.29.11007 Boehringer Ingelheim Investigational Site
🇺🇸Cincinnati, Ohio, United States
1222.29.11009 Boehringer Ingelheim Investigational Site
🇺🇸Skillman, New Jersey, United States
1222.29.49007 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.29.49004 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1222.29.36004 Boehringer Ingelheim Investigational Site
🇭🇺Zalaegerszeg, Hungary
1222.29.43002 Boehringer Ingelheim Investigational Site
🇦🇹Schlüsslberg, Austria
1222.29.42001 Boehringer Ingelheim Investigational Site
🇸🇰Bardejov, Slovakia
1222.29.42004 Boehringer Ingelheim Investigational Site
🇸🇰Nitra, Slovakia
1222.29.38003 Boehringer Ingelheim Investigational Site
🇸🇮Golnik, Slovenia
1222.29.42002 Boehringer Ingelheim Investigational Site
🇸🇰Martin, Slovakia
1222.29.42003 Boehringer Ingelheim Investigational Site
🇸🇰Spisska Nova Ves, Slovakia