Safety, Tolerability and Pharmacokinetics of BI 44370 TA Oral Drinking Solution in Healthy Male Volunteers
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02215018
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
To evaluate the safety, tolerability and pharmacokinetics of single rising oral doses of BI 44370 TA in healthy male volunteers, to compare a drinking solution vs. a tablet formulation and to assess intra-individual pharmacokinetic (PK) variability by re-dosing two further doses.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 56
Inclusion Criteria
-
Healthy males according to the following criteria:
Based upon a complete medical history, including the physical examination, vital signs (BP, PR, RR and body temperature), 12-lead ECG, clinical laboratory tests
-
Age ≥21 and Age ≤50 years
-
Body Mass Index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
-
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 Blood Pressure (BP), Pulse Rate (PR), Respiratory rate (RR) , body temperature and Electrocardiogram(ECG)) deviating from normal and of clinical relevance
- Any evidence of a clinically relevant concomitant disease
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Surgery of the gastrointestinal tract (except appendectomy)
- 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 drug or its excipients)
- Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
- Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
- Participation in another trial with an investigational drug within two months prior to administration or during the trial
- Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
- Inability to refrain from smoking on trial days
- Alcohol abuse (more than 60 g/day)
- Drug abuse
- Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
- Excessive physical activities (within one week prior to administration or during the trial)
- Any laboratory value outside the reference range that is of clinical relevance
- Inability to comply with dietary regimen of trial site
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms);
- A history of additional risk factors for Torsade des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
- Not willing to use adequate contraception (condom use plus another form of contraception e.g. spermicide, oral contraceptive taken by female partner, sterilisation, intrauterine device) during the whole study period from the time of the first intake of study drug until three months after the last intake
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BI 44370 TA tablet BI 44370 TA tablet - Placebo solution Placebo solution - BI 44370 TA solution BI 44370 TA solution - Placebo tablet Placebo tablet -
- Primary Outcome Measures
Name Time Method Number of patients with adverse events up to 10 days after last drug administration Number of patients with clinically significant findings in vital signs up to 10 days after last drug administration Assessment of tolerability by investigator on a 4-point scale up to 10 days after last drug administration Number of patients with clinically significant findings in laboratory tests up to 10 days after last drug administration Number of patients with clinically significant findings in ECG up to 10 days after last drug administration
- Secondary Outcome Measures
Name Time Method %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation) up to 72 hours after drug administration MRTp.o. (mean residence time of the analyte in the body after oral administration) up to 72 hours after drug administration Cmax (maximum measured concentration of the analyte in plasma) up to 72 hours after drug administration AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2) up to 72 hours after drug administration fet1/t2 (the fractional excretion of the analyte in the time interval from t1 to t2) up to 24 hours after drug administration AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) up to 72 hours after drug administration CL/F (total/apparent clearance of the analyte in plasma after extravascular administration) up to 72 hours after drug administration λz (the terminal rate constant) up to 72 hours after drug administration tmax (time from dosing to maximum measured concentration) up to 72 hours after drug administration tz (time of last measurable concentration of the analyte in plasma) up to 72 hours after drug administration t1/2 (terminal half-life of the analyte in plasma) up to 72 hours after drug administration Aet1/t2 (total quantity of analyte excreted in the urine in the time interval from t1 to t2) up to 24 hours after drug administration 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) up to 72 hours after drug administration Vz/F (apparent volume of distribution during the terminal phase tz following an extravascular dose) up to 72 hours after drug administration CLR,t1/t2 (the renal clearance of the analyte in the time interval from t1 to t2) up to 24 hours after drug administration