Pharmacokinetics of the Fixed Dose Combination of Tiotropium Plus BI 54903 Versus the Combination of the Monoproducts of Tiotropium and BI 54903 in Healthy Volunteers

Study Overview
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Brief Summary
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The primary objective is to compare the systemic exposure to tiotropium and CD 1857 after treatment with the fixed dose combination (fixed dose combination (FDC), Treatment A) of tiotropium plus BI 54903 (ethanolic solution for inhalation (EIS), Respimat (RMT) B) with the systemic exposure following inhalation of the free combination (Treatment B) of tiotropium (aqueous solution for inhalation (AIS), RMT A) plus BI 54903 (EIS, RMT B), when administered once-daily over 21 days via Respimat(R) (RMT). The secondary objectives are: to compare the systemic exposure to tiotropium and CD 1857 after single dose administration of FDC and of the free combination of tiotropium/BI 54903 to compare the systemic exposure to BI 54903 after a single dose and at steady state after multiple doses of the FDC and of the free combination of tiotropium/BI 54903 to compare the safety and tolerability of tiotropium and BI 54903 when administered as FDC and as free dose combination, respectively

Official Title
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An Open Label, Randomised, Two-way Crossover Phase I Study to Assess Safety, Tolerability and Pharmacokinetics of the Fixed Dose Combination of Tiotropium Plus BI 54903 Via Respimat® B Versus the Combination of the Monoproducts of Tiotropium Via Respimat® A and BI 54903 Via Respimat® B in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tiotropium
* Drug: Tiotropium
* Drug: BI 54903
* Drug: BI 54903


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests. Age 21 to 50 years. Exclusion criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders History or evidence of relevant psychiatric disorders or neurological disorders History or evidence of relevant autonomic dysfunction (orthostatic hypotension, fainting spells or blackouts) Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) Intake of any prescription drugs or over-the-counter (over the counter (OTC)) medication (vitamins, herbal supplements, dietary supplements) with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (more than 10 cigarettes daily)

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: Tiotropium medium dose<br>Oral inhalation daily for 21 days | Drug: Tiotropium<br>* Medium dose of oral inhalation<br>|
| Experimental: Treatment A: BI 54903 high dose<br>Oral inhalation daily for 21 days | Drug: BI 54903<br>* Medium dose of oral inhalation<br>|
| Experimental: Treatment B: Tiotropium medium dose<br>Oral inhalation daily for 21 days | Drug: Tiotropium<br>* Medium dose of oral inhalation<br>|
| Experimental: Treatment C: BI 54903 high dose<br>Oral inhalation daily for 21 days | Drug: BI 54903<br>* Medium dose of oral inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration time curve of CD 1857 in plasma over a uniform dosing interval τ (AUCτ,ss) |  | on several time points until day 22 | 
| Maximum concentration of CD 1857 in plasma at steady state (Cmax,ss) |  | on several time points until day 22 | 
| AUCτ,ss for Tiotropium |  | on several time points until day 22 | 
| Cmax,ss for Tiotropium |  | on several time points until day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCτ,ss for BI 54903 |  | on several time points until day 22 | 
| Cmax,ss for BI 54903 |  | on several time points until day 22 | 
| Ae0-24 (Amount of analyte that is eliminated in urine) for tiotropium |  | on Day 1 and 21 | 
| Change in physical examination |  | 9 weeks | 
| Change in vital signs |  | 9 weeks | 
| Change in 12-lead electrocardiogram |  | 9 weeks | 
| Change in clinical laboratory tests |  | 9 weeks | 
| Occurrence of Adverse Events |  | 9 weeks | 
| Assessment of tolerability by the investigator |  | 9 weeks |