Healthy
Conditions
Brief summary
Study to investigate safety and tolerability of single, inhaled doses (2.5 μg, 5 μg, 10 μg, 20 μg and 40 μg) of BI 1744 CL in free dose combination with tiotropium bromide 5 μg (for doses up to and including 20 μg BI 1744 CL) and 10 μg (for doses of 20 μg and 40 μg BI 1744 CL), both administered by Respimat® in healthy male volunteers. Also, to investigate the pharmacokinetics of BI 1744 BS and tiotropium bromide in such combinations, to explore their dose proportionality, and to explore the pharmacodynamic effects of the treatments on selected metabolic and respiratory parameters
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
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 measurement, and clinical laboratory tests. Absence of any clinically relevant abnormality. Absence of any 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. 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 randomization 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 randomization 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 (regularly more than 40 g alcohol per day for men) 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 randomization 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 Additionally, following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in potassium | up to 6 hours after drug administration | — |
| Assessment of tolerability by investigator on a 4-point scale | 12 days after drug administration | — |
| Change in Airway resistance (Raw) | up to 24 hours after drug administration | measured by whole-body plethysmography |
| Change in specific conductance (sGaw) | up to 24 hours after drug administration | measured by whole-body plethysmography |
| Change in Cyclic aminomonophosphate (cAMP) | up to 6 hours after drug administration | — |
| Number of participants with abnormal findings in physical examination | up to 12 days after drug administration | — |
| Number of participants with abnormal changes in laboratory parameters | up to 12 days after drug administration | — |
| Number of participants with clinically significant changes in vital signs | up to 12 days after drug administration | blood pressure (BP), pulse rate (PR), respiratory rate (RR) |
| Number of participants with adverse events | up to 12 days after drug administration | — |
| Number of participants with clinically significant changes in 12-lead ECG | up to 12 days after drug administration | cardiac axis, heart rate, PQ interval, QRS interval, uncorrected QT interval, HR-corrected QT-interval according to Bazett and Fridericia |
| Number of abnormal findings on oropharyngeal inspection | up to 24 hours after drug administration | — |
| Number of abnormal findings on pulmonary auscultation | up to 24 hours after drug administration | — |
Secondary
| Measure | Time frame |
|---|---|
| fet1-t2 (fraction of BI 1744 BS and tiotropium eliminated in urine from time point t1 to time point t2) | up to 96 hours after drug administration |
| CLR,t1-t2 (renal clearance of BI 1744 BS and tiotropium from the time point t1 until the time point t2) | up to 96 hours after drug administration |
| Cmax (maximum measured concentration of BI 1744 BS and tiotropium in plasma) | up to 96 hours after drug administration |
| tmax (time from dosing to maximum measured concentration) | up to 96 hours after drug administration |
| AUC0-∞ (area under the concentration-time curve of BI 1744 BS and tiotropium in plasma over the time interval from 0 extrapolated to infinity) | up to 96 hours after drug administration |
| AUC0-tz (area under the concentration-time curve of the analyte salmeterol in plasma over the time interval from 0 to the time of the last quantifiable data point) | up to 96 hours after drug administration |
| %AUCtz-∞ (percentage of the extrapolated part of the total AUC0-∞) | up to 96 hours after drug administration |
| λz (terminal rate constant in plasma) | up to 96 hours after drug administration |
| t1/2 (terminal half-life of BI 1744 BS and tiotropium in plasma) | up to 96 hours after drug administration |
| MRTih (mean residence time of BI 1744 BS and tiotropium in the body after inhalation) | up to 96 hours after drug administration |
| CL/F (apparent clearance of BI 1744 BS and tiotropium in plasma after extravascular administration) | up to 96 hours after drug administration |
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) | up to 96 hours after drug administration |
| Aet1-t2 (amount of BI 1744 BS and tiotropium eliminated in urine from the time point t1 to time point t2) | up to 96 hours after drug administration |
Outcome results
None listed