Clinical trial NCT02215018: Safety, Tolerability and Pharmacokinetics of BI 44370 TA Oral Drinking Solution in Healthy Male Volunteers
Official title: Safety, Tolerability and Pharmacokinetics of BI 44370 TA Oral Drinking Solution in Healthy Male Volunteers (Dose Range: 5 - 800 mg). A Double-blind (Within Dose Groups), Randomised, Placebo-controlled Within Dose Groups, Single Rising Dose Study, Including Re-dosing at 100 mg and 500 mg (Solution) and at 200 mg (Four 50 mg Tablets)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-13
Enrollment: 56
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Age ≥21 and Age ≤50 years
3. Body Mass Index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
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 Blood Pressure (BP), Pulse Rate (PR), Respiratory rate (RR) , body temperature and Electrocardiogram(ECG)) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. Surgery of the gastrointestinal tract (except appendectomy)
5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
6. History of relevant orthostatic hypotension, fainting spells or blackouts
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
9. 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
10. 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
11. Participation in another trial with an investigational drug within two months prior to administration or during the trial
12. Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day)
13. Inability to refrain from smoking on trial days
14. Alcohol abuse (more than 60 g/day)
15. Drug abuse
16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
17. Excessive physical activities (within one week prior to administration or during the trial)
18. Any laboratory value outside the reference range that is of clinical relevance
19. Inability to comply with dietary regimen of trial site
20. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms);
21. A history of additional risk factors for Torsade des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
22. 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

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: up to 10 days after last drug administration
measure: Number of patients with clinically significant findings in vital signs
timeFrame: up to 10 days after last drug administration
measure: Number of patients with clinically significant findings in laboratory tests
timeFrame: up to 10 days after last drug administration
measure: Number of patients with clinically significant findings in ECG
timeFrame: up to 10 days after last drug administration
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: up to 10 days after last drug administration
Secondary outcomes:
measure: Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: up to 72 hours after drug administration
measure: tmax (time from dosing to maximum measured concentration)
timeFrame: up to 72 hours after drug administration
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 72 hours after drug administration
measure: %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
timeFrame: up to 72 hours after drug administration
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 72 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 72 hours after drug administration
measure: tz (time of last measurable concentration of the analyte in plasma)
timeFrame: up to 72 hours after drug administration
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: up to 72 hours after drug administration
measure: MRTp.o. (mean residence time of the analyte in the body after oral administration)
timeFrame: up to 72 hours after drug administration
measure: CL/F (total/apparent clearance of the analyte in plasma after extravascular administration)
timeFrame: up to 72 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase tz following an extravascular dose)
timeFrame: up to 72 hours after drug administration
measure: λz (the terminal rate constant)
timeFrame: up to 72 hours after drug administration
measure: Aet1/t2 (total quantity of analyte excreted in the urine in the time interval from t1 to t2)
timeFrame: up to 24 hours after drug administration
measure: fet1/t2 (the fractional excretion of the analyte in the time interval from t1 to t2)
timeFrame: up to 24 hours after drug administration
measure: CLR,t1/t2 (the renal clearance of the analyte in the time interval from t1 to t2)
timeFrame: up to 24 hours after drug administration
Other outcomes:
Locations:
Study officials:
References: