Tiotropium Respimat Pharmacokinetic Study in COPD
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Registration Number
- NCT01222533
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The purpose of this study is compare the effect of different doses of tiotropium delivered by the HandiHaler and Respimat device on lung function. Additionally, the study will investigate the pharmacokinetic profile of these different doses. Studying the pharmacokinetic profile shows what happens to the medication in the body over a period of hours and provides information on potential effects of the medication.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 154
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Tiotropium low Tiotropium low Tiotropium inhalation solution low dose Tiotropium medium Tiotropium medium Tiotropium inhalation solution medium dose Tiotropium high Tiotropium high Tiotropium inhalation solution high dose Tiotropium 18mcg Tiotropium 18mcg Tiotropium inhalation powder 18mcg Tiotropium placebo Tiotropium placebo Placebo inhalation solution
- Primary Outcome Measures
Name Time Method Area Under the Curve 0 to 6 Hours at Steady-state (AUC0-6h,ss) Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing. AUC0-6h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 6 hours post-dose at steady-state. AUC0-6h,ss was calculated using the linear up/log down algorithm.
Maximum Plasma Concentration at Steady-state (Cmax,ss) Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing. Cmax,ss is the maximum measured concentration of tiotropium in plasma at steady-state.
- Secondary Outcome Measures
Name Time Method Trough Forced Expiratory Volume in One Second (FEV1) at the End of Each Treatment Period 4 weeks Defined as FEV1 measured just prior to the last administration of the morning dose of the randomised treatment. Means are adjusted for sequence, patients within sequences, period and treatment.
FEV1 Area Under the Curve 0 to 6 Hours (AUC0-6h) at the End of Each Treatment Period 4 weeks FEV1 AUC0-6h calculated from zero time to 6 hours using the trapezoidal rule divided by 6 hours. Trough FEV1 will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.
FEV1 Area Under the Curve 0 to 3 Hours (AUC0-3h) at the End of Each Treatment Period 4 weeks FEV1 AUC0-3h calculated from zero time to 3 hours using the trapezoidal rule divided by 3 hours. Trough FEV1 will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.
Trough Forced Vital Capacity (FVC) at the End of Each Treatment Period 4 weeks Defined as the pre-dose FVC measured just prior to the last administration of the morning dose of the randomised treatment. Means are adjusted for sequence, patients within sequences, period and treatment.
FVC AUC0-6h at the End of Each Treatment Period 4 weeks FVC AUC0-6h calculated from zero time to 6 hours using the trapezoidal rule divided by 6 hours. Trough FVC will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.
FEV1 at Each Planned Time at the End of Each Treatment Period 4 weeks Means are adjusted for period, planned time, period\*planned time, patient\*planned time and patient\*treatment\*planned time.
FVC at Each Planned Time at the End of Each Treatment Period 4 weeks Means are adjusted for period, planned time, period\*planned time, patient\*planned time and patient\*treatment\*planned time.
Area Under the Curve 0 to 1 Hour at Steady-state (AUC0-1h,ss) Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing. AUC0-1h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 1 hour post-dose at steady-state. AUC0-1h,ss was calculated using the linear up/log down algorithm.
Time to Maximum Plasma Concentration at Steady-state (Tmax,ss) Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 min before first dosing of study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 h, 2 h, 4 h and 6 h post dosing. Tmax,ss is the time from dosing to the maximum concentration of tiotropium in plasma-venous blood at steady-state.
Amount of Drug Eliminated in Urine at Steady-state (Ae0-6h,ss) Based on urine sampling for PK assessments done at 4 weeks in the following intervals: -1 to 0 hour (h), 0 to 2 h and 2 to 6 h post-dosing. Total quantity of the analyte that is excreted in urine over the time interval 0 to 6 hours at steady state.
Pre-dose Plasma Concentration at Steady-state (Cpre,ss) Based on blood sampling for PK assessments done at 4 weeks at the following time point: 5 minutes (min) before first dosing of study drug (baseline) Cpre,ss is the measured concentration of tiotropium in plasma before dosing at steady-state.
Renal Clearance at Steady-state (CL R,0-6h,ss) Based on blood and urine sampling for PK assessments done at 4 weeks over 6 h post dosing. Renal clearance of the drug over the time interval 0 to 6 hours at steady-state. CL R,0-6h,ss was calculated as the quotient of Ae0-6h,ss and AUC0-6h,ss.
Minimum Plasma Concentration at Steady-state (Cmin,ss) Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 min before first dosing of study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 h, 2 h, 4 h and 6 h post dosing. Cmin,ss is the minimum measured concentration of tiotropium in plasma at steady-state.
FVC AUC0-3h at the End of Each Treatment Period 4 weeks FVC AUC0-3h calculated from zero time to 3 hours using the trapezoidal rule divided by 3 hours. Trough FVC will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.
Trial Locations
- Locations (11)
205.458.32002 Boehringer Ingelheim Investigational Site
🇧🇪Hasselt, Belgium
205.458.49001 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany
205.458.32003 Boehringer Ingelheim Investigational Site
🇧🇪Genk, Belgium
205.458.32001 Boehringer Ingelheim Investigational Site
🇧🇪Gent, Belgium
205.458.35802 Boehringer Ingelheim Investigational Site
🇫🇮Tampere, Finland
205.458.31001 Atrium Medisch Centrum Parkstad
🇳🇱Heerlen, Netherlands
205.458.31002 Ommelander ziekenhuis groep, locatie Lucas
🇳🇱Winschoten, Netherlands
205.458.45001 Boehringer Ingelheim Investigational Site
🇩🇰Copenhagen K, Denmark
205.458.45003 Boehringer Ingelheim Investigational Site
🇩🇰København NV, Denmark
205.458.45002 Boehringer Ingelheim Investigational Site
🇩🇰Odense C, Denmark
205.458.35801 Boehringer Ingelheim Investigational Site
🇫🇮Helsinki, Finland