Combination of Orally Inhaled BI1744CL/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease ( COPD)

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).

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: BI 1744 CL/tiotropium bromide fixed dose combination; Device: Respimat® Inhaler; Drug: tiotropium bromide

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • 1237.4.0203 Boehringer Ingelheim Investigational Site
  • Ontario
    • Mississauga, Ontario, Canada
      • 1237.4.0201 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1237.4.0202 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1237.4.0205 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1237.4.0208 Boehringer Ingelheim Investigational Site
  • Quebec
    • Sainte-Foy, Quebec, Canada
      • 1237.4.0206 Boehringer Ingelheim Investigational Site
    • Sherbrooke, Quebec, Canada
      • 1237.4.0204 Boehringer Ingelheim Investigational Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • 1237.4.0207 Boehringer Ingelheim Investigational Site
• Germany
  • Berlin, Germany
    • 1237.4.4903 Boehringer Ingelheim Investigational Site
  • Erfurt, Germany
    • 1237.4.4907 Boehringer Ingelheim Investigational Site
  • Gauting, Germany
    • 1237.4.4902 Boehringer Ingelheim Investigational Site
  • Halle, Germany
    • 1237.4.4908 Boehringer Ingelheim Investigational Site
  • Neuruppin, Germany
    • 1237.4.4906 Boehringer Ingelheim Investigational Site
  • Rüdersdorf, Germany
    • 1237.4.4904 Boehringer Ingelheim Investigational Site
  • Weinheim, Germany
    • 1237.4.4901 Boehringer Ingelheim Investigational Site
• United States
  • California
    • Riverside, California, United States
      • 1237.4.0118 Boehringer Ingelheim Investigational Site
    • San Diego, California, United States
      • 1237.4.0103 Boehringer Ingelheim Investigational Site
  • Colorado
    • Wheat Ridge, Colorado, United States
      • 1237.4.0115 Boehringer Ingelheim Investigational Site
  • Florida
    • Clearwater, Florida, United States
      • 1237.4.0105 Boehringer Ingelheim Investigational Site
    • Deland, Florida, United States
      • 1237.4.0110 Boehringer Ingelheim Investigational Site
    • Tampa, Florida, United States
      • 1237.4.0117 Boehringer Ingelheim Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States
      • 1237.4.0104 Boehringer Ingelheim Investigational Site
  • Minnesota
    • Edina, Minnesota, United States
      • 1237.4.0120 Boehringer Ingelheim Investigational Site
    • Minneapolis, Minnesota, United States
      • 1237.4.0112 Boehringer Ingelheim Investigational Site
  • Missouri
    • St. Charles, Missouri, United States
      • 1237.4.0119 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States
      • 1237.4.0114 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • 1237.4.0102 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States
      • 1237.4.0111 Boehringer Ingelheim Investigational Site
    • Spartanburg, South Carolina, United States
      • 1237.4.0106 Boehringer Ingelheim Investigational Site
    • Spartanburg, South Carolina, United States
      • 1237.4.0107 Boehringer Ingelheim Investigational Site
  • Tennessee
    • Knoxville, Tennessee, United States
      • 1237.4.0123 Boehringer Ingelheim Investigational Site
  • Texas
    • Killeen, Texas, United States
      • 1237.4.0122 Boehringer Ingelheim Investigational Site
    • New Braunfels, Texas, United States
      • 1237.4.0109 Boehringer Ingelheim Investigational Site
  • Virginia
    • Richmond, Virginia, United States
      • 1237.4.0108 Boehringer Ingelheim Investigational Site
  • Washington
    • Spokane, Washington, United States
      • 1237.4.0116 Boehringer Ingelheim Investigational Site
    • Tacoma, Washington, United States
      • 1237.4.0121 Boehringer Ingelheim Investigational Site
  • West Virginia
    • Morgantown, West Virginia, United States
      • 1237.4.0101 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions

2. 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

3. Male or female patients, 40 years of age or older
4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years
5. 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
6. 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

Exclusion Criteria:

1. Patients with a significant disease other than COPD
2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
3. Patients with a history of asthma or a total blood eosinophil count >= 600/mm3.
4. 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)
5. 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
6. Patients who have undergone thoracotomy with pulmonary resection
7. 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.
8. Pregnant or nursing women
9. 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
10. Patients who have previously been randomized in this study or are currently participating in another study
11. Patients who are unable to comply with pulmonary medication restrictions prior to randomization
12. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 1744 CL low dose/tiotropium bromide; BI 1744 CL low dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation	Drug: BI 1744 CL/tiotropium bromide fixed dose combination; BI 1744 CL plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation; Device: Respimat® Inhaler
Experimental: BI1744CL medium dose/tiotropium bromide; BI 1744 CL medium dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation	Drug: BI 1744 CL/tiotropium bromide fixed dose combination; BI 1744 CL plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation; Device: Respimat® Inhaler
Experimental: BI 1744 CL high dose/tiotropium bromide; BI 1744 CL high dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation	Drug: BI 1744 CL/tiotropium bromide fixed dose combination; BI 1744 CL plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation; Device: Respimat® Inhaler
Experimental: tiotropium bromide; tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation	Device: Respimat® Inhaler; Drug: tiotropium bromide; tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline and 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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).	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).	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).	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.	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.	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.	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.	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.	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.	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).	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).	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).	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).	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).	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.	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.	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.	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.	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.	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.	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.	Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: June 10, 2008
• First Submitted That Met QC Criteria: June 11, 2008
• First Posted (Estimate): June 12, 2008

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: July 20, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides; Olodaterol
• Other Study ID Numbers: 1237.4; EudraCT No: 2007-005087-26