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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Salmeterol capsule via Handihaler - low | Experimental |
| |
| Salmeterol capsule via Handihaler - high | Experimental |
| |
| Salmeterol via Serevent® Diskus® | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Salmeterol capsule - low | Drug |
| ||
| Salmeterol capsule - high |
| 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 |
| 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) |
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Inclusion Criteria:
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)
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| ID | Term |
|---|---|
| D000068299 | Salmeterol Xinafoate |
| ID | Term |
|---|---|
| D000420 | Albuterol |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 |
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| Drug |
|
| Salmeterol via Serevent® Diskus® | Drug |
|
| 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 |
| Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |