Tiotropium and Salmeterol PK Study in COPD Patients

Study Overview
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Brief Summary
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The primary objective of this study is to characterize the pharmacokinetics (i.e. systemic exposure to tiotropium and salmeterol) of tiotropium qd + salmeterol qd or bid versus tiotropium qd and salmeterol bid following 4-week treatment periods in patients with chronic obstructive pulmonary disease (COPD).

Official Title
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A Randomised, Open-label, 4-way Crossover Study to Characterize the Pharmacokinetics, Safety and Efficacy of FDC Tiotropium/Salmeterol, Tiotropium, Salmeterol and a Free Combination of Tiotropium Plus Salmeterol Following 4-week Treatment Periods in Patients With COPD.

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium+Salmeterol
* Drug: Salmeterol
* Drug: Tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD patients of >= 40 years old with moderate to severe COPD who are current or ex-smokers with a smoking history of at least 10 pack-years Exclusion Criteria: Recent history of myocardial infarction, life-threatening cardiac arrhythmia or hospitalisation for cardiac failure History of asthma Malignancy requiring treatment within past 5 years Life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis Known active tuberculosis Pregnant or nusing women Known hypersensitivity to components of the study medication

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
Intervention Model: Crossover Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tiotropium+Salmeterol|nan|
|Drug: Salmeterol|nan|
|Drug: Tiotropium|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve (AUC0-∞ ) of tiotropium in plasma |  | 16 weeks | 
| Maximum measured concentration of tiotropium in plasma (Cmax) |  | 16 weeks | 
| Amount of tiotropium that was eliminated in urine (Ae0-8) from time point 0 to 8 hours post-inhalation |  | 16 weeks | 
| AUC0-∞ of salmeterol in plasma |  | 16 weeks | 
| Cmax salmeterol in plasma |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration time curve (AUCt1-t2) of tiotropium and salmeterol in plasma over the time interval t1 to t2 for time intervals 0 to 4, 0 to 6, and 0 to 8 hours after inhalation (AUC0-4, AUC0-6, and AUC0-8) |  | 16 weeks | 
| Time from dosing to the maximum concentration of tiotropium and salmeterol in plasma (tmax) |  | 16 weeks | 
| Terminal rate constant in plasma (λz) |  | 16 weeks | 
| Terminal half-life (t½) of tiotropium and salmeterol in plasma) |  | 16 weeks | 
| Mean residence time (MRTih) of tiotropium and salmeterol in the body after inhalational administration |  | 16 weeks | 
| Apparent clearance (CL/F) of tiotropium and salmeterol in plasma after extravascular administration) |  | 16 weeks | 
| Apparent volume of distribution (Vz/F) during the terminal phase (λz) following an extravascular dose) |  | 16 weeks | 
| Amount of tiotropium that is eliminated in urine from the time point t1 to time point t2 (Aet1-t2) (Ae0-2, Ae2-4, Ae4-8, Ae0-8) |  | 16 weeks | 
| Fraction of tiotropium eliminated in urine from time point t1 to time point t2 (fet1-t2) (fe0-2, fe2-4, fe4-8, fe0-8) |  | 16 weeks | 
| Renal clearance of tiotropium from the time point t1 until the time point t2 (CLR,t1-t2) (CLR,0-2, CLR, 2-4, CLR,4-8, CLR,0-8) |  | 16 weeks | 
| All adverse events |  | 20 weeks | 
| Blood pressure (seated) recorded in conjunction with 12-lead ECG recordings pre-dose and following the morning dose of randomized treatment |  | 20 weeks | 
| Number of patients with abnormalities in routine blood chemistry, haematology and urinalysis |  | 16 weeks | 
| Trough forced expiratory volume in one second (FEV1) |  | 16 weeks | 
| Trough forced vital capacity (FVC) |  | 16 weeks | 
| FEV1 area under the curve 0 to 8 hours (FEV1 AUC0-8h) |  | 16 weeks | 
| FVC area under the curve 0 to 8 hours (FVC AUC0-8h) |  | 16 weeks | 
| Individual FEV1and FVC measurements at each time point at the end of each 4-week treatment period. |  | 16 weeks |