Pharmacokinetics of Salmeterol (Serevent®) After Inhalation With Metered Dose Inhaler (MDI) and Diskus® in Healthy Male Volunteers

Study Overview
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Brief Summary
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To compare the systemic drug exposure of 100 μg Serevent ® Diskus ® with that of 50 μg Serevent ® MDI with sufficient precision so that in combination with a second trial it can be demonstrated that the systemic drug exposure of a new formulation of salmeterol xinafoate is not superior to that of Serevent ® MDI To test a system of ordered null hypotheses regarding the exposure of two dose levels of Serevent ® Diskus ® and Serevent ® MDI To get data about the systemic drug exposure of 25 μg Serevent ® MDI and of 50 μg Serevent ® Diskus ®

Official Title
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A Randomised, Open-label Four-way Crossover Study to Evaluate Pharmacokinetics of Salmeterol (Serevent®) After Inhalation of a 25 μg and 50 μg Single Dose (Metered Dose Inhaler) and a 50 μg and 100 μg Single Dose (Diskus®) in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Salmeterol Diskus low
* Drug: Salmeterol Diskus high
* Drug: Salmeterol MDI low
* Drug: Salmeterol MDI high


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males 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 ECG (electrocardiogram) , clinical laboratory tests 1.1 No finding deviating from normal and of clinical relevance 1.2 No evidence of a clinically relevant concomitant disease Age ≥21 and ≤50 years BMI ≥18.5 and <30 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation. Exclusion Criteria: Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts. Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (>24 hours) within at least 1 month or less than 10 half-lives of the respective drug prior to administration or during the trial. Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial. Participation in another trial with an investigational drug within 2 months prior to administration or during the trial. Smoker (more than 10 cigarettes or three cigars or three pipes per day) Inability to refrain from smoking on trial days Alcohol abuse (more than 60 g/day) Drug abuse Blood donation (more than 100 mL within 4 weeks prior to administration or during the trial) Excessive physical activities (within 1 week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of study centre Exclusion criterion specific for this study: Asthma or history of pulmonary hyperreactivity Allergy / hypersensitivity to Lactose monohydrate Hyperthyrosis Allergic rhinitis in need of treatment Cardiac arrhythmia Paroxysmal tachycardia (> 100 beats per minute) Aortic stenosis

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

Sexes Eligible for Study
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Male

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: Salmeterol MDI low<br> | Drug: Salmeterol MDI low<br> <br> |
| Active Comparator: Salmeterol MDI high<br> | Drug: Salmeterol MDI high<br> <br> |
| Experimental: Salmeterol Diskus low<br> | Drug: Salmeterol Diskus low<br> <br> |
| Experimental: Salmeterol Diskus high<br> | Drug: Salmeterol Diskus high<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | Up to 6 hours after drug administration | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | Up to 6 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | Up to 6 hours after drug administration | 
| AUCt1-t2 (Area under the concentration time curve of the analyte in plasma over the time interval t1 to t2) |  | Up to 6 hours after inhalation | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | Up to 6 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | Up to 6 hours after drug administration | 
| t½ (terminal half-life of the analyte in plasma) |  | Up to 6 hours after drug administration | 
| MRTinh (mean residence time of the analyte in the body after inhalational administration) |  | Up to 6 hours after drug administration | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) |  | Up to 6 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | Up to 6 hours after drug administration | 
| Aet1-t2 (amount of analyte that was eliminated in urine from the time interval t1 to t2) |  | Up to 6 hours after inhalation | 
| fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2) |  | Up to 6 hours after inhalation | 
| CLR,t1-t2 (renal clearance of the analyte in plasma from the time point t1 to t2) |  | Up to 6 hours after inhalation | 
| Number of participants with abnormal findings in physical examination |  | Up to 15 days after last drug administration | 
| Number of participants with clinically significant changes in vital signs |  | Up to 15 days after last drug administration | 
| Number of participants with abnormal findings in ECG |  | Up to 15 days after last drug administration | 
| Number of participants with abnormal changes in clinical laboratory parameters |  | Up to 15 days after last drug administration | 
| Number of participants with adverse events |  | Up to 15 days after last drug administration |