Single Dose Ranging Study of BI 1744 CL (Olodaterol) in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Primary objective: To investigate bronchodilator effect and safety of single doses of BI 1744 CL inhaled via Respimat inhaler, Secondary objective: to characterize pharmacokinetics of BI 1744 CL. Olodaterol dose 40 mcg was investigated only in the open-label extension part for additional PK assessments which are not defined as primary or secondary endpoints.

Official Title
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Single Dose Preliminary Dose-ranging and Safety in Patients With COPD

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: single dose of 5 mcg
* Drug: single dose of placebo
* Drug: single dose of 40 mcg
* Drug: single dose of 20 mcg
* Drug: single dose of 2 mcg
* Drug: single dose of 10 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of chronic obstructive pulmonary disease Smoking history of more than 10-pack years Exclusion criteria: History of asthma, allergic rhinitis, myocardial infarction or unstable of life-threatening cardiac arrhythmias Marked baseline prolongation of QT/QTc interval

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: olodaterol 2 mcg<br>solution for inhalation | Drug: single dose of 2 mcg<br>* solution for inhalation<br>|
| Experimental: olodaterol 5 mcg<br>solution for inhalation | Drug: single dose of 5 mcg<br>* solution for inhalation<br>|
| Experimental: olodaterol 10 mcg<br>solution for inhalation | Drug: single dose of 10 mcg<br>* solution for inhalation<br>|
| Experimental: olodaterol 20 mcg<br>solution for inhalation | Drug: single dose of 20 mcg<br>* solution for inhalation<br>|
| Experimental: olodaterol 40 mcg<br>solution for inhalation | Drug: single dose of 40 mcg<br>* solution for inhalation<br>|
| Placebo Comparator: placebo<br>solution for inhalation | Drug: single dose of placebo<br>* solution for inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in One Second (FEV1) at 24 Hours After a Single-dose of Study Treatment | Forced expiratory volume in one second (FEV1) at 24 hours after a single-dose of study treatment. Means are adjusted with test-day baseline, patient, treatment, and period as fixed effects. Test-day baseline value was defined as the value at 10 minutes before inhalation of study medication. | 24 hours post-dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC 0 - 3 Hours | The FEV1 AUC was calculated as the area under the curve above zero as the horizontal axis from zero time to 3 hours, using the trapezoidal rule divided by 3 hours to give the results in litres. The test-day baseline (defined as the pulmonary function test (PFT) at 10 minutes before inhalation of study medication) was assigned to time zero. | -10 minutes (min), 30min, 1 hour (h), 2h and 3h post-dosing | 
| FEV1 AUC 0 - 12 Hours | The FEV1 AUC was calculated as the area under the curve above zero as the horizontal axis from zero time to 12 hours, using the trapezoidal rule divided by 12 hours to give the results in litres. The test-day baseline (defined as the pulmonary function test (PFT) at 10 minutes before inhalation of study medication) was assigned to time zero. | -10 minutes (min), 30min, 1 hour (h), 2h, 3h, 4h, 6h, 8h, 10h and 12h post-dosing | 
| FEV1 AUC 0 - 24 Hours | The FEV1 AUC was calculated as the area under the curve above zero as the horizontal axis from zero time to 24 hours, using the trapezoidal rule divided by 24 hours to give the results in litres. The test-day baseline (defined as the pulmonary function test (PFT) at 10 minutes before inhalation of study medication) was assigned to time zero. | -10 minutes (min), 30min, 1 hour (h), 2h, 3h, 4h, 6h, 8h, 10h, 12h, 14h, 22h, 23h and 24h post-dosing | 
| FEV1 AUC 12 - 24 Hours | The FEV1 AUC was calculated as the area under the curve above zero as the horizontal axis from 12 hours to 24 hours, using the trapezoidal rule divided by 12 hours to give the results in litres. The test-day baseline (defined as the pulmonary function test (PFT) at 10 minutes before inhalation of study medication) was assigned to time zero. | 12h, 14h, 22h, 23h and 24h post-dosing | 
| Peak FEV1 From 0 to 3 Hours | Peak FEV1 was defined as the maximum values of FEV1 from 0 to 3 hours. | 0 to 3 hours post-dosing | 
| Peak Forced Vital Capacity (FVC) From 0 to 3 Hours | Peak FVC was defined as the maximum values of FVC from 0 to 3 hours. | 0 to 3 hours post-dosing | 
| Time to Peak Bronchodilator Response | A bronchodilator response was considered to have been achieved if an FEV1 measurement of at least 12% greater than the test-day baseline value was recorded at any time during the first 3 hours of observation after dosing. | 0 to 3 hours post-dosing | 
| Time to Onset of Response | Onset of the bronchodilator response after a single dose of study treatment was defined as the linear interpolation of the time of the first bronchodilator response and the time of the observation just prior to the first bronchodilator response (even if that is the baseline observation). If none of the FEV1 values in the first 3 hours after dosing exceeded 12% of the pre-dose value, then the onset was set to 3 hours plus 1 minute. | 0 to 3 hours post-dosing | 
| Number of Patients Requiring Rescue Medication on a Test-day | Number of Patients Requiring Rescue Medication on a Test-day. Salbutamol inhalation aerosol MDI (Ventolin®, 100 μg/actuation) was provided for use as rescue medication. Administration of rescue medication can occur at any point during the pulmonary function testing as deemed necessary by the patient or the investigator. | Visits 1,2,4,5,6 | 
| Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG | Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events (cardiac disorders and investigations). | 2 weeks | 
| Laboratory Testing: Average Change From Baseline of Potassium and Calcium | Laboratory testing: Average change from baseline of potassium and calcium measured on test-days | Baseline and Visit 6 |