Healthy
Conditions
Brief summary
Assessment of the relative bioavailability of a fixed dose combination of tiotropium and salmeterol compared to a free dose combination of the marketed products of tiotropium and salmeterol (Spiriva® and Serevent® Diskus®). Assessment of the relative bioavailability of a fixed dose combination of tiotropium and salmeterol compared to tiotropium and salmeterol administered as individual mono substances from the marketed products. Assessment of safety and tolerability of the fixed combination of tiotropium and salmeterol in a PE (Polyethylene) capsule administered via the HandiHaler® 2
Interventions
Fixed dose combination of tiotropium 7.5 μg and salmeterol 25 μg inhalation powder, PE capsule via HandiHaler®
DRUGSpiriva®
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male based upon a complete medical history, including the physical examination, regarding vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG (electrocardiogram) 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 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 GCP (Good Clinical Practice) and the local legislation
Exclusion criteria
1. Any finding of the medical examination (including BP, PR, and ECG measurements) deviating from normal and of clinical relevance 2. Evidence of a clinically relevant concomitant disease 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders 5. History of relevant orthostatic hypotension, fainting spells or blackouts 6. Chronic or relevant acute infections 7. History of relevant allergy/hypersensitivity (including allergy to the drug or its excipients) as judged clinically relevant by the investigator 8. 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 randomisation 9. 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 enrolment in the study or during the study 10. Participation in another trial with an investigational drug within 2 months prior to randomisation 11. Smoker (\>10 cigarettes or \>3 cigars or \>3 pipes/day) 12. Inability to refrain from smoking on trial days as judged by the investigator 13. Alcohol abuse (more than 40 g alcohol a day) 14. Drug abuse 15. Blood donation (more than 100 mL blood within 4 weeks prior to randomisation or during the trial) 16. Excessive physical activities within 1 week prior to randomisation or during the trial 17. Any laboratory value outside the reference range that is of clinical relevance 18. Inability to comply with dietary regimen of the study centre The following
Design outcomes
Primary
| Measure | 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 |
| Ae0-8 (urinary excretion of tiotropium over an 8 hour interval) | Up to 8 hours after drug administration |
Secondary
| Measure | Time frame |
|---|---|
| Cmax (maximum measured concentration of tiotropium in blood plasma) | Up to 8 hours after drug administration |
| AUCt1-t2 (area under the concentration time curve in plasma over the time interval t1 to t2) | up to 8 hours after inhalation |
| tmax (time from dosing to the maximum concentration of 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 in plasma) | Up to 8 hours after drug administration |
| MRTih (mean residence time in the body after inhalational administration) | Up to 8 hours after drug administration |
| CL/F (apparent clearance of 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 |
| fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) | up to 8 hours after inhalation |
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) | up to 8 hours after inhalation |
| Number of participants with abnormal findings in physical examination | up to 90 days after first drug administration |
| Number of participants with clinically significant changes in vital signs | up to 90 days after first drug administration |
| Number of participants with abnormal findings in 12-lead ECG | up to 90 days after first drug administration |
| Number of participants with abnormal changes in clinical laboratory parameters | up to 90 days after first drug administration |
| Number of participants with adverse events | up to 90 days after first drug administration |
| Tolerability assessed by investigator on a 4-point scale | up to 90 days after first drug administration |
| Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2 | up to 8 hours after inhalation |
| AUC0-tz (area under the concentration-time curve in plasma over the time interval from 0 to the time of the last quantifiable data point) | Up to 8 hours after drug administration |
| AUC0-∞ (area under the concentration-time curve of tiotropium in blood plasma over the time interval from 0 extrapolated to infinity) | Up to 8 hours after drug administration |
Outcome results
None listed