Relative Bioavailability of of Olodaterol and Ketoconazole

Study Overview
=================
Brief Summary
-----------------
This clinical trial is intended to investigate a possible effect of the p-gp inhibitor ketoconazole on the bioavailability of olodaterol

Official Title
-----------------
Relative Bioavailability of 10 mcg Olodaterol (Solution for Inhalation Administered With the Respimat) at Steady State Alone or in Combination With Multiple Doses of 400 mg q.d. Ketoconazole (Tablet) in Healthy Male and Female Volunteers (an Open Label, Fixed Sequence, Phase I Study)

Conditions
-----------------
Healthy, Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
-----------------
* Drug: BI 1744
* Drug: BI 1744
* Drug: Ketoconazole
* Drug: Ketoconazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Healthy male and female volunteers Exclusion criteria

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 1744 10 mcg<br>solution for oral inhalation | Drug: BI 1744<br>* 10 mcg solution for oral inhalation<br>Drug: Ketoconazole<br>* 400 mg tablet<br>|
| Experimental: Ketoconazole 400 mg<br>tablet | Drug: BI 1744<br>* 10 mcg solution for oral inhalation<br>Drug: Ketoconazole<br>* 400 mg tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Curve From 0 to 1 Hour at Steady State (AUC0-1,ss) | AUC0-1,ss represents the area under the concentration curve of olodaterol in plasma from 0 to time t=1 hour at steady state, where t is defined as the latest time-point where at least 2/3 of the subjects in both treatment periods reveal quantifiable plasma concentrations of olodaterol. The geometric mean is actually the adjusted geometric mean. The geometric coefficient of variation (gCV) is the intra-individual gCV. | Day 8 of period 1 and day 14 of period 2 | 
| Maximum Concentration at Steady State (Cmax,ss) | Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state. The geometric mean is actually the adjusted geometric mean. The geometric coefficient of variation (gCV) is the intra-individual gCV. | Day 8 of period 1 and day 14 of period 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) | tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state. | Day 8 of period 1 and day 14 of period 2 | 
| Fraction of Urine Excretion From 0 to 24 Hours at Steady State (fe0-24,ss) | fe0-24,ss represents the fraction of olodaterol eliminated in urine from time point 0 to 24 hours after administration at steady state. | Day 8 of period 1 and day 14 of period 2 | 
| Amount of the Analyte Excreted in Urine From 0 to 24 Hours at Steady State (Ae0-24,ss) | Ae0-24,ss represents the amount of olodaterol and olodaterol glucuronide that is eliminated in urine from the time 0 to 24h after administration at steady state. The geometric mean is actually the adjusted geometric mean. The geometric coefficient of variation (gCV) is the intra-individual gCV. | Day 8 of period 1 and day 14 of period 2 | 
| Area Under Curve From 0 to 8 Hours at Steady State (AUC0-8,ss) | AUC0-8,ss represents the area under the concentration curve of olodaterol glucuronide in plasma from 0 to time t=8 at steady state, where t is defined as the latest time-point where at least 2/3 of the subjects in both treatment periods reveal quantifiable plasma concentrations of the analyte. The geometric mean is actually the adjusted geometric mean. The geometric coefficient of variation (gCV) is the intra-individual gCV. | Day 8 of period 1 and day 14 of period 2 | 
| 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 worsening of baseline conditions were reported as treatment-induced Adverse Events. | First administration of trial medication until 6 days after last administration of trial medication | 
| Assessment of Tolerability by the Investigator | The investigator assessed tolerability based on adverse events and the laboratory evaluation at the end-of-trial examination. The investigator classified the overall tolerability according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'. | End of period 1 and end of period 2 |