Determining Optimal Free Dose Combination of Tiotropium Bromide and BI 1744 CL in Chronic Obstructive Pulmonary Disease (COPD)
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Registration Number
- NCT01040403
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study is to determine the optimum once daily dose of BI 1744 CL and tiotropium in free dose combination (delivered by the Respimat inhaler) after four week treatment in patients with COPD.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 233
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description olodaterol (BI 1744) low and placebo olodaterol (BI 1744) low low dose inhaled olodaterol orally once daily from the Respimat inhaler olodaterol (BI 1744) low and placebo Placebo low dose inhaled olodaterol orally once daily from the Respimat inhaler olodaterol (BI 1744) low and placebo Respimat low dose inhaled olodaterol orally once daily from the Respimat inhaler olodaterol (BI 1744) low and low tio low tiotropium bromide low dose inhaled olodaterol and low dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) low and low tio Respimat low dose inhaled olodaterol and low dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) low and medium tio medium tiotropium bromide low dose inhaled olodaterol and medium dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) low and medium tio Respimat low dose inhaled olodaterol and medium dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) low and high tio high tiotropium bromide low dose inhaled olodaterol and high dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) low and high tio Respimat low dose inhaled olodaterol and high dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) high and placebo Placebo high dose inhaled olodaterol orally once daily from the Respimat inhaler Olodaterol (BI 1744) high and high tio high tiotropium bromide high dose inhaled olodaterol and high dose inhaled tiotropium, both from the Respimat inhaler and once daily Olodaterol (BI 1744) high and high tio Respimat high dose inhaled olodaterol and high dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) high and placebo Respimat high dose inhaled olodaterol orally once daily from the Respimat inhaler Olodaterol (BI 1744) high and low tio low tiotropium bromide high dose inhaled olodaterol and low dose inhaled tiotropium, both from the Respimat inhaler and once daily Olodaterol (BI 1744) high and low tio Respimat high dose inhaled olodaterol and low dose inhaled tiotropium, both from the Respimat inhaler and once daily Olodaterol (BI 1744) high and medium tio medium tiotropium bromide high dose inhaled olodaterol and medium dose inhaled tiotropium, both from the Respimat inhaler and once daily Olodaterol (BI 1744) high and medium tio Respimat high dose inhaled olodaterol and medium dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) low and low tio olodaterol (BI 1744) low low dose inhaled olodaterol and low dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) low and medium tio olodaterol (BI 1744) low low dose inhaled olodaterol and medium dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) low and high tio olodaterol (BI 1744) low low dose inhaled olodaterol and high dose inhaled tiotropium, both from the Respimat inhaler and once daily olodaterol (BI 1744) high and placebo olodaterol (BI 1744) high high dose inhaled olodaterol orally once daily from the Respimat inhaler Olodaterol (BI 1744) high and low tio olodaterol (BI 1744) high high dose inhaled olodaterol and low dose inhaled tiotropium, both from the Respimat inhaler and once daily Olodaterol (BI 1744) high and medium tio olodaterol (BI 1744) high high dose inhaled olodaterol and medium dose inhaled tiotropium, both from the Respimat inhaler and once daily Olodaterol (BI 1744) high and high tio olodaterol (BI 1744) high high dose inhaled olodaterol and high dose inhaled tiotropium, both from the Respimat inhaler and once daily
- Primary Outcome Measures
Name Time Method Trough FEV1 Response Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29 Adjusted means of the trough forced expiratory volume in one second (FEV1) response (L) after four weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
- Secondary Outcome Measures
Name Time Method Trough Forced Vital Capacity (FVC) Response Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29 Adjusted means of trough FVC (forced vital capacity) response \[L\] after 4 weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FEV1 AUC 0-3h and FEV1 AUC 0-6h Response Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29 Adjusted means of forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-3 hour and AUC 0-6 hour responses \[L\] after 4 weeks treatment calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FEV1 AUC 0-3h Response After the First Dose Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1 Adjusted means of Forced Expiratory Volume in One Second (FEV1) Area Under Curve (AUC) 0-3h response \[L\] after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FEV1 Peak 0-3h Response Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29 Adjusted means of the FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response \[L\] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FEV1 Peak 0-3h Response After the First Dose Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1 Adjusted means of the FEV1 peak 0-3h response \[L\] after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FVC AUC 0-3h and FEV1 AUC 0-6h Responses Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29 Adjusted means of the FVC AUC 0-3h and AUC 0-6h responses \[L\] after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FVC AUC 0-3h Response After First Dose Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on days 1 Adjusted means of the FVC AUC 0-3h response \[L\] after first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FVC Peak 0-3h Response Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29 Adjusted means of the FVC peak 0-3h response \[L\] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FVC Peak 0-3h Response After the First Dose Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1 Adjusted mean of the FVC peak 0-3h response \[L\] after the first dose. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
PEF AUC 0-3h and AUC 0-6h Responses Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29 Adjusted means of the Peak Expiratory Flow (PEF) AUC 0-3h and AUC 0-6h responses in Litres / minute (L/min) after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
PEF AUC 0-3h Response After the First Dose Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1 Adjusted means of the Area under the curve from 0 to 3 h response in Litres / minutes of the peak expiratory flow after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
PEF Peak 0-3h Response Baseline 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29 Adjusted means of the peak expiratory flow from 0 to 3 hours (PEF peak 0-3h) response in L/min after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
PEF Peak 0-3h Response After the First Dose Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1 Adjusted means of the Peak Expiratory flow from 0 to 3 hours response in L/min after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Individual FEV1 Measurements at Each Time Point on Day 29 Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29 Adjusted means of the FEV1 measurements \[L\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Individual FVC Measurements at Each Time Point on Day 29 Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29 Adjusted means of the FVC measurements \[L\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Individual PEF Measurements at Each Time Point on Day 29 Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29 Adjusted means of the PEF measurements \[L/min\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Weekly Mean Number of Puffs of Rescue Medication Used Per Day Weeks 1 and 4 Adjusted means of the weekly mean number of puffs of rescue medication during the whole day : the rescue medication was a salbutamol \[albuterol\] dose (100 mcg per puff).
Physicians Global Evaluation Days 1 and 29 Adjusted means of the Physicians Global Evaluation of the patient's respiratory condition on days 1 and 29.
The score was evaluated on a 8-points scale :
* Poor : 1,2
* Fair : 3,4
* Good : 5,6
* Excellent : 7,8Patients Global Rating Day 29 Adjusted means of the Global Rating of the patients' health (respiratory condition) on day 29.
The score was evaluated on a 7-point scale :
* 1 : very much better
* 2 : much better
* 3 : a little better
* 4 : no change
* 5 : a little worse
* 6 : much worse
* 7 : very much worsePulse Rate Recorded in Conjunction With Spirometry Baseline and 30 min post-dose on day 29 Pulse rate recorded in conjunction with spirometry change from baseline at 30 minutes post-dose on day 29 in beats per minute (bpm).
Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry Baseline and 30 min post-dose on day 29 Systolic and diastolic blood pressure recorded in conjunction with spirometry change from baseline on day 29 in millimetres of mercury (mmHg).
Trial Locations
- Locations (33)
1237.18.49005 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1237.18.02003 Boehringer Ingelheim Investigational Site
🇨🇦Point Claire, Quebec, Canada
1237.18.46003 Boehringer Ingelheim Investigational Site
🇸🇪Boden, Sweden
1237.18.49004 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt, Germany
1237.18.49011 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1237.18.31008 Boehringer Ingelheim Investigational Site
🇳🇱Eindhoven, Netherlands
1237.18.49012 Boehringer Ingelheim Investigational Site
🇩🇪Bamberg, Germany
1237.18.46002 Boehringer Ingelheim Investigational Site
🇸🇪Göteborg, Sweden
1237.18.02009 Boehringer Ingelheim Investigational Site
🇨🇦Quebec, Canada
1237.18.49008 Boehringer Ingelheim Investigational Site
🇩🇪Wiesloch, Germany
1237.18.46001 Boehringer Ingelheim Investigational Site
🇸🇪Lund, Sweden
1237.18.31004 Boehringer Ingelheim Investigational Site
🇳🇱Almelo, Netherlands
1237.18.31001 Boehringer Ingelheim Investigational Site
🇳🇱Groningen, Netherlands
1237.18.31006 Boehringer Ingelheim Investigational Site
🇳🇱Amsterdam, Netherlands
1237.18.31007 Boehringer Ingelheim Investigational Site
🇳🇱Hengelo, Netherlands
1237.18.31005 Boehringer Ingelheim Investigational Site
🇳🇱Hoorn, Netherlands
1237.18.31002 Boehringer Ingelheim Investigational Site
🇳🇱Veldhoven, Netherlands
1237.18.31003 Boehringer Ingelheim Investigational Site
🇳🇱Zutphen, Netherlands
1237.18.49007 Boehringer Ingelheim Investigational Site
🇩🇪Mannheim, Germany
1237.18.49003 Boehringer Ingelheim Investigational Site
🇩🇪Weinheim, Germany
1237.18.02005 Boehringer Ingelheim Investigational Site
🇨🇦Grimsby, Ontario, Canada
1237.18.02001 Boehringer Ingelheim Investigational Site
🇨🇦Mississauga, Ontario, Canada
1237.18.02004 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
1237.18.02002 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
1237.18.02008 Boehringer Ingelheim Investigational Site
🇨🇦Toronto, Ontario, Canada
1237.18.02007 Boehringer Ingelheim Investigational Site
🇨🇦Sherbrooke, Quebec, Canada
1237.18.02011 Boehringer Ingelheim Investigational Site
🇨🇦Saskatoon, Saskatchewan, Canada
1237.18.49009 Boehringer Ingelheim Investigational Site
🇩🇪Aschaffenburg, Germany
1237.18.49010 Boehringer Ingelheim Investigational Site
🇩🇪Koblenz, Germany
1237.18.49002 Boehringer Ingelheim Investigational Site
🇩🇪Rüdersdorf, Germany
1237.18.49001 Boehringer Ingelheim Investigational Site
🇩🇪Potsdam, Germany
1237.18.49006 Boehringer Ingelheim Investigational Site
🇩🇪Rodgau-Dudenhofen, Germany
1237.18.46004 Boehringer Ingelheim Investigational Site
🇸🇪Stockholm, Sweden