Pharmacokinetics of Salmeterol Via HandiHaler® in Healthy Male Volunteers

Study Overview
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Brief Summary
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The objective of this study is to investigate if the systemic drug exposure of at least 25 μg and perhaps 50 μg salmeterol presented as inhalation powder in PE capsules and administered via HandiHaler® 2 does not exceed that of 50 μg Serevent® Diskus® and to investigate safety and tolerability of salmeterol presented as inhalation powder in PE capsules and administered via HandiHaler® 2

Official Title
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A Randomised, Open-label Three-way Crossover Study to Evaluate the Pharmacokinetics of Salmeterol After Inhalation of a 25 μg and 50 μg Single Dose (Inhalation Powder, Hard PE Capsule for HandiHaler®2) and a 50 μg Single Dose (Serevent® Diskus®) in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Salmeterol capsule - low
* Drug: Salmeterol capsule - high
* Drug: Salmeterol via Serevent® Diskus®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male based upon a complete medical history, including the physical examination, regarding vital signs ((Blood Pressure (BP), Pulse Rate (PR)), 12-lead ECG measurement, and clinical laboratory tests. There is no finding deviating from normal and of clinical relevance. There is 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: Any finding of the medical examination (including BP, PR, and ECG measurements) deviating from normal and of clinical relevance Evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 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 relevant allergy/hypersensitivity (including allergy to the drug or its excipients) as judged clinically relevant 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 randomization 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 randomization Participation in another trial with an investigational drug within 2 months prior to randomization Smoker (>10 cigarettes or >3 cigars or >3 pipes/day) Inability to refrain from smoking on trial days as judged by the investigator Alcohol abuse (more than 60 g alcohol a day) Drug abuse Blood donation (more than 100 mL blood within 4 weeks prior to randomization or during the trial) Excessive physical activities within 1 week prior to randomization or during the trial Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of the study centre The following exclusion criteria are specific for this study due to the known class side effect profile of ß2-mimetics: Asthma or history of pulmonary hyperreactivity Hyperthyrosis Allergic rhinitis in need of treatment Clinically relevant cardiac arrhythmia Paroxysmal tachycardia (>100 beats per minute)

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 capsule via Handihaler - low<br> | Drug: Salmeterol capsule - low<br> <br> |
| Experimental: Salmeterol capsule via Handihaler - high<br> | Drug: Salmeterol capsule - high<br> <br> |
| Active Comparator: Salmeterol via Serevent® Diskus®<br> | Drug: Salmeterol via Serevent® Diskus®<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 salmeterol in blood plasma over the time interval from 0 extrapolated to infinity) |  | up to 8 hours after drug administration | 
| Cmax (maximum measured concentration of salmeterol in blood plasma) |  | up to 8 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz (area under the concentration-time curve of salmeterol in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | up to 8 hours after drug administration | 
| AUCt1-t2 (area under the concentration time curve of salmeterol in plasma over the time interval t1 to t2) |  | up to 8 hours after drug administration | 
| tmax (time from dosing to the maximum concentration of salmeterol in plasma) |  | up to 8 hours after drug administration | 
| λz (terminal rate constant in plasma) |  | up to 8 hours after drug administration | 
| t½ (terminal half-life of salmeterol in plasma) |  | up to 8 hours after drug administration | 
| MRTih (mean residence time of salmeterol in the body after inhalational administration) |  | up to 8 hours after drug administration | 
| CL/F (apparent clearance of salmeterol in the plasma after extravascular administration) |  | up to 8 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase (λz) following an extravascular dose) |  | up to 8 hours after drug administration | 
| Number of patients with abnormal changes in laboratory parameters |  | up to 14 days following the last drug administration | 
| Number of patients with clinically significant changes in vital signs | Blood Pressure, Pulse Rate | up to 14 days following the last drug administration | 
| Number of patients with clinically significant changes in 12-lead ECG parameters |  | up to 14 days following the last drug administration | 
| Number of patients with adverse events |  | up to 14 days following the last drug administration | 
| Assessment of tolerability by investigator on a 4-point scale |  | 14 days following the last drug administration |