Clinical trial NCT02254226: Pharmacokinetics of Salmeterol (Serevent®) After Inhalation With Metered Dose Inhaler (MDI) and Diskus® in Healthy Male Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-01
Enrollment: 26
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 1. 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
2. To test a system of ordered null hypotheses regarding the exposure of two dose levels of Serevent ® Diskus ® and Serevent ® MDI
3. To get data about the systemic drug exposure of 25 μg Serevent ® MDI and of 50 μg Serevent ® Diskus ®


Eligibility criteria: Inclusion Criteria:

1. 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
2. Age ≥21 and ≤50 years
3. BMI ≥18.5 and \<30 kg/m2 (Body Mass Index)
4. 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:

1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
2. Surgery of gastrointestinal tract (except appendectomy)
3. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
4. History of relevant orthostatic hypotension, fainting spells or blackouts.
5. Chronic or relevant acute infections
6. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
7. 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.
8. 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.
9. Participation in another trial with an investigational drug within 2 months prior to administration or during the trial.
10. Smoker (more than 10 cigarettes or three cigars or three pipes per day)
11. Inability to refrain from smoking on trial days
12. Alcohol abuse (more than 60 g/day)
13. Drug abuse
14. Blood donation (more than 100 mL within 4 weeks prior to administration or during the trial)
15. Excessive physical activities (within 1 week prior to administration or during the trial)
16. Any laboratory value outside the reference range that is of clinical relevance
17. Inability to comply with dietary regimen of study centre

    Exclusion criterion specific for this study:
18. Asthma or history of pulmonary hyperreactivity
19. Allergy / hypersensitivity to Lactose monohydrate
20. Hyperthyrosis
21. Allergic rhinitis in need of treatment
22. Cardiac arrhythmia
23. Paroxysmal tachycardia (\> 100 beats per minute)
24. Aortic stenosis

Primary outcomes:
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: Up to 6 hours after drug administration
measure: Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: Up to 6 hours after drug administration
Secondary outcomes:
measure: 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)
timeFrame: Up to 6 hours after drug administration
measure: AUCt1-t2 (Area under the concentration time curve of the analyte in plasma over the time interval t1 to t2)
timeFrame: Up to 6 hours after inhalation
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma)
timeFrame: Up to 6 hours after drug administration
measure: λz (terminal rate constant in plasma)
timeFrame: Up to 6 hours after drug administration
measure: t½ (terminal half-life of the analyte in plasma)
timeFrame: Up to 6 hours after drug administration
measure: MRTinh (mean residence time of the analyte in the body after inhalational administration)
timeFrame: Up to 6 hours after drug administration
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
timeFrame: Up to 6 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
timeFrame: Up to 6 hours after drug administration
measure: Aet1-t2 (amount of analyte that was eliminated in urine from the time interval t1 to t2)
timeFrame: Up to 6 hours after inhalation
measure: fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)
timeFrame: Up to 6 hours after inhalation
measure: CLR,t1-t2 (renal clearance of the analyte in plasma from the time point t1 to t2)
timeFrame: Up to 6 hours after inhalation
measure: Number of participants with abnormal findings in physical examination
timeFrame: Up to 15 days after last drug administration
measure: Number of participants with clinically significant changes in vital signs
timeFrame: Up to 15 days after last drug administration
measure: Number of participants with abnormal findings in ECG
timeFrame: Up to 15 days after last drug administration
measure: Number of participants with abnormal changes in clinical laboratory parameters
timeFrame: Up to 15 days after last drug administration
measure: Number of participants with adverse events
timeFrame: Up to 15 days after last drug administration
Other outcomes:
Locations:
Study officials:
References: