Pulmonary Disease, Chronic ObstructivePhase 2NCT00696020
Combination of Orally Inhaled BI1744CL/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease ( COPD)
A Phase 2 study testing BI 1744 CL/tiotropium bromide fixed dose combination, tiotropium bromide and Respimat® Inhaler in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 37 sites in 3 countries.
Trial summary
The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL administered with 5 micrograms tiotropium bromide solution for inhalation, delivered by the Respimat inhaler, once daily for four weeks in patients with chronic obstructive pulmonary disease (COPD). Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- BI 1744 CL/tiotropium bromide fixed dose combination, tiotropium bromide and Respimat® Inhaler
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 37 sitesin 3 countries
- Study dates
- Jun 2008to Feb 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions
- All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
- Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 greater or equal 30% of predicted normal and <80% of predicted normal and a post-bronchodilator FEV1 / FVC <70% at Visit 1
- Male or female patients, 40 years of age or older
- Patients must be current or ex-smokers with a smoking history of more than 10 pack years
- 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).
- Further inclusion criteria apply
Who cannot join
- Patients with a significant disease other than COPD
- Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
- Patients with a history of asthma or a total blood eosinophil count >= 600/mm3.
- 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 QTcF* 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, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years, 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
Show all 13Show fewer
- Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
- Pregnant or nursing women
- Women of childbearing potential not using two effective method of birth control (one barrier and one non-barrier). 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 two 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
- Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit
- Further exclusion criteria apply
Trial locations and contacts
37 sites in 3 countries.
37 sites in 3 countries
United States22 sites
1237.4.0111 Boehringer Ingelheim Investigational Site
Charleston, South Carolina
1237.4.0105 Boehringer Ingelheim Investigational Site
Clearwater, Florida
1237.4.0104 Boehringer Ingelheim Investigational Site
Coeur d'Alene, Idaho
1237.4.0110 Boehringer Ingelheim Investigational Site
DeLand, Florida
1237.4.0120 Boehringer Ingelheim Investigational Site
Edina, Minnesota
1237.4.0122 Boehringer Ingelheim Investigational Site
Killeen, Texas
1237.4.0123 Boehringer Ingelheim Investigational Site
Knoxville, Tennessee
1237.4.0112 Boehringer Ingelheim Investigational Site
Minneapolis, Minnesota
1237.4.0101 Boehringer Ingelheim Investigational Site
Morgantown, West Virginia
1237.4.0109 Boehringer Ingelheim Investigational Site
New Braunfels, Texas
1237.4.0102 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania
1237.4.0114 Boehringer Ingelheim Investigational Site
Raleigh, North Carolina
1237.4.0108 Boehringer Ingelheim Investigational Site
Richmond, Virginia
1237.4.0118 Boehringer Ingelheim Investigational Site
Riverside, California
1237.4.0119 Boehringer Ingelheim Investigational Site
Saint Charles, Missouri
1237.4.0103 Boehringer Ingelheim Investigational Site
San Diego, California
1237.4.0106 Boehringer Ingelheim Investigational Site
Spartanburg, South Carolina
1237.4.0107 Boehringer Ingelheim Investigational Site
Spartanburg, South Carolina
1237.4.0116 Boehringer Ingelheim Investigational Site
Spokane, Washington
1237.4.0121 Boehringer Ingelheim Investigational Site
Tacoma, Washington
1237.4.0117 Boehringer Ingelheim Investigational Site
Tampa, Florida
1237.4.0115 Boehringer Ingelheim Investigational Site
Wheat Ridge, Colorado
Canada8 sites
1237.4.0201 Boehringer Ingelheim Investigational Site
Mississauga, Ontario
1237.4.0206 Boehringer Ingelheim Investigational Site
Sainte-Foy, Quebec
1237.4.0207 Boehringer Ingelheim Investigational Site
Saskatoon, Saskatchewan
1237.4.0204 Boehringer Ingelheim Investigational Site
Sherbrooke, Quebec
1237.4.0202 Boehringer Ingelheim Investigational Site
Toronto, Ontario
1237.4.0205 Boehringer Ingelheim Investigational Site
Toronto, Ontario
1237.4.0208 Boehringer Ingelheim Investigational Site
Toronto, Ontario
1237.4.0203 Boehringer Ingelheim Investigational Site
Winnipeg, Manitoba
Germany7 sites
1237.4.4903 Boehringer Ingelheim Investigational Site
Berlin
1237.4.4907 Boehringer Ingelheim Investigational Site
Erfurt
1237.4.4902 Boehringer Ingelheim Investigational Site
Gauting
1237.4.4908 Boehringer Ingelheim Investigational Site
Halle
1237.4.4906 Boehringer Ingelheim Investigational Site
Neuruppin
1237.4.4904 Boehringer Ingelheim Investigational Site
Rüdersdorf
1237.4.4901 Boehringer Ingelheim Investigational Site
Weinheim
About this study
Official title: Randomised, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of 3 Doses of Orally Inhaled BI 1744 CL, Each in Fixed Dose Combination With 5 Microgram Tiotropium Bromide (Delivered by the Respimat Inhaler) Compared With 5 Microgram Tiotropium Bromide Monoproduct (Delivered by the Respimat Inhaler) in Patients With COPD
The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL administered with 5 micrograms tiotropium bromide solution for inhalation, delivered by the Respimat inhaler, once daily for four weeks in patients with chronic obstructive pulmonary disease (COPD).
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- BI 1744 CL/tiotropium bromide fixed dose combination, tiotropium bromide, Respimat® Inhaler
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 1744 CL/tiotropium bromide fixed dose combinationDrug
BI 1744 CL plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
tiotropium bromideDrug
tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation
Respimat® InhalerDevice
| Study group | Role | What they receive |
|---|---|---|
| BI 1744 CL low dose/tiotropium bromide | Experimental | BI 1744 CL low dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation Receives: Drug: BI 1744 CL/tiotropium bromide fixed dose combination; Device: Respimat® Inhaler |
| BI1744CL medium dose/tiotropium bromide | Experimental | BI 1744 CL medium dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation Receives: Drug: BI 1744 CL/tiotropium bromide fixed dose combination; Device: Respimat® Inhaler |
| BI 1744 CL high dose/tiotropium bromide | Experimental | BI 1744 CL high dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation Receives: Drug: BI 1744 CL/tiotropium bromide fixed dose combination; Device: Respimat® Inhaler |
| tiotropium bromide | Experimental | tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation Receives: Drug: tiotropium bromide; Device: Respimat® Inhaler |
What is being measured
The primary outcome is the main question the study is designed to answer.
Trough FEV1 Response [L] After 4 Weeks of Treatment
Trough FEV1 (Forced expiratory volume in 1 second) was defined as the mean of the two FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
Measured: Baseline and 4 weeks
Secondary outcomes (26)
Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.
Trough FEV1 (forced expiratory volume in 1 second) was defined as the mean of the 2 FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 15.
Measured: Baseline, 1 week and 2 weeks
Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment
Trough FVC (forced vital capacity) was defined as the mean of the 2 FVC values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FVC response was defined as the change from baseline in trough FVC. Baseline FVC was defined as the mean of the 2 pre-treatment FVC values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: Baseline, 1 week, 2 weeks and 4 weeks
FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
Response is defined as change from the baseline value. AUC(0-3h) (area under the curve) was calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks
FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.
FVC (forced vital capacity) AUC(0-3h) response is defined as change from the baseline value. AUC(0-3h) was calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres. Baseline FVC was defined as the mean of the 2 pre-treatment FVC values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks
PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.
PEF (peak expiratory flow rate L/min) AUC(0-3h) response is defined as change from the baseline value. AUC(0-3h) will be calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres/min. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks
FEV1 AUC(0-6h) Response [L] After 4 Weeks of Treatment
FEV1 (forced expiratory volume in 1 second) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
Measured: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
FVC AUC(0-6h) Response [L] After 4 Weeks of Treatment
FVC (forced vital capacity) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Measured: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
PEF AUC(0-6h) Response [L] After 4 Weeks of Treatment
PEF (peak expiratory flow rate L/min) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Measured: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
FEV1 Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
FEV1 (forced expiratory volume in 1 second) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
FVC Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
FVC (forced vital capacity) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
PEF Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
PEF (peak expiratory flow rate L/min) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
FEV1 and PEF (Unsupervised) AUC(0-6h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
AUC(0-6h) for FEV1, and PEF (unsupervised) were not studied because the pertinent information from the unsupervised pulmonary function tests was for the time interval from 9 to 12 hours post-dosing.
Measured: After first administration, 1 week, 2 weeks and 4 weeks
FEV1 (Unsupervised) AUC(6-12h) Response [L] After First Administration and 1,2 and 4 Weeks of Treatment
FEV1 (forced expiratory volume in 1 second) AUC(6-12h) response is defined as change from the baseline value. AUC(6-12h) will be calculated as the area under the curve from 6 to 12 hours on the various test days using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: 6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
PEF (Unsupervised) AUC(6-12h) Response [L/Min] After First Administration and 1,2 and 4 Weeks of Treatment
PEF (peak expiratory flow rate L/min) AUC(6-12h) response is defined as change from the baseline value. AUC(6-12h) will be calculated as the area under the curve from 6 to 12 hours on the various test days using the trapezoidal rule, divided by the full duration (6 hours) to report in litres/min. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.
The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
Comparisons between groups are presented for Day 29.
Measured: 6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
Weekly Mean Pre-dose Morning PEF [L/Min]
The patient will record twice daily peak flow measurements using an Asthma Monitor®Am2+ (AM2+) device. Morning measurements will be performed immediately upon arising after the patient has cleared out mucus, prior to administration of trial and/or rescue medication.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Measured: Throughout the 4 week treatment period
Weekly Mean Evening PEF [L/Min]
The patient will record twice daily peak flow measurements using an AM2+ device. The evening measurement will be performed at bedtime.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Measured: Throughout the 4 weeks treatment period
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day
The means are adjusted, Based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Measured: Throughout the 4 weeks treatment period
Physician's Global Evaluation
Measured a 8-point scale, from 1 (poor) to 8 (excellent), as judged by the physician, over 4 weeks of treatment.
The physician made a global evaluation at the end of the Baseline Period (Test Day 1) and at each visit thereafter. These assessments were made prior to pulmonary function testing and reflected the physician's opinion of the patient's overall clinical condition. This evaluation was based on the need for concomitant medication, number and severity of COPD exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, and other relevant clinical observations.
The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).
Measured: 1 week, 2 weeks and 4 weeks
Patient's Global Rating
Patient's Global Rating at the end of the 4 week treatment period.
Patients rated their health (respiratory condition) at Day 29 (compared to the day before they commenced treatment with study medication) on a 7-point scale as "very much better (1), much better (2), a little better (3), no change (4), a little worse (5), much worse (6), or very much worse (7)". The assessment was made prior to pulmonary function testing and all other study procedures. The Patient's Global Rating was also completed before the Physician's Global Evaluation.
The means are adjusted, based on an ANCOVA with terms for treatment, centre (centre random, treatment effect fixed).
Measured: 4 weeks
Clinically Significant Anormalities (Laboratory Data); Marked Changes From Baseline for Vital Signs, Notable Change in ECG and New Onset of ECG Abnormalities
Possible clinically significant anormalities (laboratory data); marked changes from baseline for vital signs, notable change in ECG and new onset of ECG abnormalities. New abnormal findings or worsening of baseline conditions were reported as Adverse Events (AEs).
All AEs with an onset after the first dose of study medication up to 21 days after the last dose of study medication were to have been assigned to the Treatment Period.
Measured: From first dose up to 21 days after last dose of study medication.
Cmax,ss Olodaterol [pg/mL]
Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss) after 4 weeks of treatment.
No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.
Measured: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Tmax,ss Olodaterol [h]
Time from last dosing to maximum concentration of Olodaterol in plasma at steady state (tmax,ss) after 4 weeks treatment.
No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.
Measured: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
AUC(0-1h,ss) Olodaterol [pg*h/mL]
Area under the concentration-time curve of Olodaterol in plasma at steady state (AUC(0-1h,ss)) from 0 to 1 hour post dosing after 4 weeks of treatment.
No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure.
Measured: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Cmax,ss Tiotropium [pg/mL]
Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss) after 4 weeks treatment.
Measured: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Tmax,ss Tiotropium [h]
Time from last dosing to maximum concentration of Tiotropium in plasma at steady state (tmax,ss) after 4 weeks of treatment.
Measured: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
AUC(0-3h,ss) Tiotropium [pg*h/mL]
Area under the concentration-time curve of Tiotropium at steady state (AUC(0-3h,ss)) from 0 to 3 hours post dosing after 4 weeks of treatment.
Measured: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00696020
- Sponsor's protocol ID
- 1237.4
- Other IDs
- EudraCT No: 2007-005087-26
- Status last verified
- Jul 2015
- First submitted
- 10 Jun 2008
- Last updated
- 13 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Maltais F, Hamilton A, Voss F, Maleki-Yazdi MR. Dose Determination for a Fixed-Dose Drug Combination: A Phase II Randomized Controlled Trial for Tiotropium/Olodaterol Versus Tiotropium in Patients with COPD. Adv Ther. 2019 Apr;36(4):962-968. doi: 10.1007/s12325-019-00911-y. Epub 2019 Mar 6.
PubMed 30843141
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of 3 Doses of Orally Inhaled BI 1744 CL, Each in Fixed Dose Combination With 5 Microgram Tiotropium Bromide (Delivered by the Respimat Inhaler) Compared With 5 Microgram Tiotropium Bromide Monoproduct (Delivered by the Respimat Inhaler) in Patients With COPD
- ClinicalTrials.gov ID
- NCT00696020
- Acronym / sponsor ID
- 1237.4
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 360 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- Feb 2009 (actual)
- First posted
- 12 Jun 2008 (estimated)
- Results
- Posted 13 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL administered with 5 micrograms tiotropium bromide solution for inhalation, delivered by the Respimat inhaler, once daily for four weeks in patients with chronic obstructive pulmonary disease (COPD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BI 1744 CL low dose/tiotropium bromide | Experimental | Drug: BI 1744 CL/tiotropium bromide fixed dose combination, Device: Respimat® InhalerBI 1744 CL low dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation |
| BI1744CL medium dose/tiotropium bromide | Experimental | Drug: BI 1744 CL/tiotropium bromide fixed dose combination, Device: Respimat® InhalerBI 1744 CL medium dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation |
| BI 1744 CL high dose/tiotropium bromide | Experimental | Drug: BI 1744 CL/tiotropium bromide fixed dose combination, Device: Respimat® InhalerBI 1744 CL high dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation |
| tiotropium bromide | Experimental | Drug: tiotropium bromide, Device: Respimat® Inhalertiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions
- All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
- Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 greater or equal 30% of predicted normal and <80% of predicted normal and a post-bronchodilator FEV1 / FVC <70% at Visit 1
- Male or female patients, 40 years of age or older
- Patients must be current or ex-smokers with a smoking history of more than 10 pack years
Key exclusion criteria (13 listed)
- Patients with a significant disease other than COPD
- Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
- Patients with a history of asthma or a total blood eosinophil count >= 600/mm3.
- 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 QTcF* 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, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years, a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, a history of significant alcohol or drug abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 1744 CL/tiotropium bromide fixed dose combinationBI 1744 CL plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation | Drug | BI 1744 CL high dose/tiotropium bromide, BI 1744 CL low dose/tiotropium bromide, BI1744CL medium dose/tiotropium bromide |
| tiotropium bromidetiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation | Drug | tiotropium bromide |
| Respimat® Inhaler | Device | BI 1744 CL high dose/tiotropium bromide, BI 1744 CL low dose/tiotropium bromide, BI1744CL medium dose/tiotropium bromide, tiotropium bromide |
Primary outcome
Trough FEV1 Response [L] After 4 Weeks of Treatment
Time frame: Baseline and 4 weeks
Trough FEV1 (Forced expiratory volume in 1 second) was defined as the mean of the two FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).
26 secondary outcomes
Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.
Time frame: Baseline, 1 week and 2 weeks
Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment
Time frame: Baseline, 1 week, 2 weeks and 4 weeks
FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
Time frame: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks
FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.
Time frame: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks
PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.
Time frame: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks
FEV1 AUC(0-6h) Response [L] After 4 Weeks of Treatment
Time frame: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
FVC AUC(0-6h) Response [L] After 4 Weeks of Treatment
Time frame: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
PEF AUC(0-6h) Response [L] After 4 Weeks of Treatment
Time frame: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
FEV1 Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
Time frame: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
FVC Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
Time frame: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
PEF Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
Time frame: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
FEV1 and PEF (Unsupervised) AUC(0-6h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
Time frame: After first administration, 1 week, 2 weeks and 4 weeks
FEV1 (Unsupervised) AUC(6-12h) Response [L] After First Administration and 1,2 and 4 Weeks of Treatment
Time frame: 6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
PEF (Unsupervised) AUC(6-12h) Response [L/Min] After First Administration and 1,2 and 4 Weeks of Treatment
Time frame: 6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
Weekly Mean Pre-dose Morning PEF [L/Min]
Time frame: Throughout the 4 week treatment period
Weekly Mean Evening PEF [L/Min]
Time frame: Throughout the 4 weeks treatment period
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day
Time frame: Throughout the 4 weeks treatment period
Physician's Global Evaluation
Time frame: 1 week, 2 weeks and 4 weeks
Patient's Global Rating
Time frame: 4 weeks
Clinically Significant Anormalities (Laboratory Data); Marked Changes From Baseline for Vital Signs, Notable Change in ECG and New Onset of ECG Abnormalities
Time frame: From first dose up to 21 days after last dose of study medication.
Cmax,ss Olodaterol [pg/mL]
Time frame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Tmax,ss Olodaterol [h]
Time frame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
AUC(0-1h,ss) Olodaterol [pg*h/mL]
Time frame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Cmax,ss Tiotropium [pg/mL]
Time frame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Tmax,ss Tiotropium [h]
Time frame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
AUC(0-3h,ss) Tiotropium [pg*h/mL]
Time frame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30843141Maltais F, Hamilton A, Voss F, Maleki-Yazdi MR. Dose Determination for a Fixed-Dose Drug Combination: A Phase II Randomized Controlled Trial for Tiotropium/Olodaterol Versus Tiotropium in Patients with COPD. Adv Ther. 2019 Apr;36(4):962-968. doi: 10.1007/s12325-019-00911-y. Epub 2019 Mar 6.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
37 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BI 1744 CL/tiotropium bromide fixed dose combination, tiotropium bromide and Respimat® Inhaler in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 37 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States, Canada, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Trough FEV1 Response [L] After 4 Weeks of Treatment (time frame: Baseline and 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00696020, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2015.