Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 11634 Solution in Healthy Male Volunteers
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Drug: PlaceboDrug: BI 11634 drinking solutionDrug: BI 11634 tablet
- Registration Number
- NCT02214914
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
First evaluation of safety, tolerability, pharmacokinetics and the pharmacodynamic effect of BI 11634 on coagulation parameters
- 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), 12-lead ECG, clinical laboratory tests
- Age ≥18 and ≤50 years
- Haemoglobin within the normal ranges
- 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
- Relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Relevant surgery of gastrointestinal tract
- History of any bleeding disorder or acute blood coagulation defect, for the subject itself or any person of his family as far as known
- History of gastric ulcera and cholecystectomy
- Occult blood in feces
- Relevant diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- History of relevant orthostatic hypotension, fainting spells or blackouts
- Relevant chronic or acute infections
- History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
- 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 based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
- Use of acetylsalicylic acid or any other non-steroidal anti-inflammatory drugs (NSAID) within 2 weeks of study start until the end of study
- Participation in another trial with an investigational drug within two months prior to administration or during the trial
- Alcohol abuse (more than 40 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
- Vulnerable subjects (e.g. persons kept in detention)
- The subject is not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
- Subjects with a history within the past 2 weeks of closed head or torso trauma or deceleration injury such as an automobile accident or fall from a significant height
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - BI 11634 drinking solution BI 11634 drinking solution single rising dose BI 11634 tablet BI 11634 tablet -
- Primary Outcome Measures
Name Time Method Number of subjects with clinically significant findings in ECG up to 10 days after drug administration Number of subjects with clinically significant findings laboratory tests up to 10 days after drug administration Assessment of tolerability by investigator on a 4-point scale up to 10 days after drug administration Number of subjects with adverse events up to 10 days after drug administration Number of subjects with clinically significant findings in vital signs (blood pressure, pulse rate) up to 10 days after drug administration
- Secondary Outcome Measures
Name Time Method λz (terminal rate constant in plasma) up to 72 hours after drug administration Maximum international normalized ratio (INR) up to 72 hours after drug administration compared between groups
Cmax (maximum measured 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 MRTpo (mean residence time of the analyte in the body after oral administration) up to 72 hours after drug administration Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) up to 72 hours after drug administration fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) up to 48 hours after drug administration Activated partial thromboplastin time (aPTT) ratios between groups up to 72 hours after drug administration AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point) up to 72 hours after drug administration CL/F (apparent clearance of the analyte in plasma after extravascular administration) up to 72 hours after drug administration Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) up to 48 hours after drug administration Time to maximum inhibition of thrombin generation BI 11634 up to 24 hours after drug administration tmax (time from dosing to maximum measured concentration) up to 72 hours after drug administration Area under the inhibition of the endogenous thrombin generation-time curve up to 24 hours after drug administration AUC0-inf (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 CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) up to 48 hours after drug administration Percent inhibition of thrombin generation by BI 11634 up to 24 hours after drug administration Maximum aPTT prolongation up to 72 hours after drug administration compared between groups
% inhibition of endogenous Factor Xa up to 72 hours after drug administration by Russel's Viper Venom test (RVV)
Percent peak inhibition of thrombin generation up to 24 hours after drug administration Percent prolongation of lag time up to 24 hours after drug administration Maximum prolongation of blood coagulation time up to 72 hours after drug administration by HepTest® (Haemachem Inc.) and COAMATIC® Heparin test (Chromogenix)