Healthy
Conditions
Brief summary
Single Rising Dose (SRD) study: First evaluation of safety, tolerability, pharmacokinetics and pharmacodynamics of BI 60732
Interventions
DRUGBI 60732
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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 Age ≤ 45 years * BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index) * Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice and the local legislation
Exclusion criteria
* Any finding of the medical examination deviating from normal and of clinical relevance. Repeated measurement of a systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg * 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 within one month or less than 10 half-lives of the respective drug prior to first study drug administration except if a relevant interaction can be ruled out * Participation in another trial with an investigational drug within 2 months prior to first study drug administration * Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day) * Alcohol abuse (average consumption of more than 30 g / day) * Drug abuse * Blood donation (more than 100 mL within four weeks prior to the start of study) * 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 de pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome) * Anaemia at screening * Subjects who in the investigator's judgement are perceived as having an increased risk of bleeding, for example because of: * Hemorrhagic disorders or bleeding diathesis * Occult blood in faeces or haematuria * Trauma or surgery within the last month or as long as an excessive risk of bleeding persists after these events, or planned surgery during trial participation * History of arteriovenous malformation or aneurysm * History of gastroduodenal ulcer disease or gastrointestinal haemorrhage * History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding * Use of drugs that may interfere with haemostasis during trial conduct (e.g. acetylsalicylic acid or other non-steroidal anti-inflammatory drugs) * Thrombocytopenia (platelet count \< 100/nL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with clinically relevant changes in vital signs (blood pressure (BP), pulse rate (PR)) | up to day 21 after start of treatment | — |
| Number of patients with clinically relevant changes in 12-lead ECG | up to day 21 after start of treatment | — |
| Number of patients with clinically relevant changes in laboratory parameters | up to day 21 after start of treatment | — |
| Number of patients with clinically relevant changes in coagulation parameters | up to 72 hours after start of treatment | Parameters: * Activated partial thromboplastin time (aPTT) * Prothrombin time (PT) * HepTest® |
| Number of patients with adverse events | up to 6 weeks | — |
| Global assessment of tolerability by investigator on a 4-point scale | up to 21 days after start of treatment | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent clearance of the analyte in plasma after extravascular administration (CL/F) | up to 264 hours after start of treatment | — |
| Amount of analyte eliminated in urine from the time point t1 to time point t2 (Aet1-t2) | up to 264 hours after start of treatment | — |
| Fraction of analyte eliminated in urine from time point t1 to time point t2 (fet1-t2) | up to 264 hours after start of treatment | — |
| Renal clearance of the analyte from the time point t1 until the time point t2 (CLR,t1-t2) | Pre-dose, up to 264 hours after start of treatment | — |
| Changes in activated partial thromboplastin time (aPTT) | Pre-dose, up to 72 hours after start of treatment | — |
| Changes in prothrombin time (PT) | Pre-dose, up to 72 hours after start of treatment | — |
| Prolongation of coagulation time by Heptest® | up to 72 hours after start of treatment | — |
| Maximum measured concentration of the analyte in plasma (Cmax) | up to 264 hours after start of treatment | — |
| Percentage inhibition of endogenous thrombin generation | up to 24 hours after start of treatment | — |
| Percentage peak inhibition of thrombin generation | up to 24 hours after start of treatment | — |
| Relative prolongation of time to maximum inhibition of thrombin generation | up to 24 hours after start of treatment | — |
| Relative prolongation of lag time of thrombin generation | up to 24 hours after start of treatment | — |
| Maximum effect (Emax) | up to 168 hours after start of treatment | — |
| Time to maximum effect (tmax) | up to 168 hours after start of treatment | — |
| Area under the effect curve (AUEC) | up to 168 hours after start of treatment | — |
| Inhibition of FXa activity | Pre-dose up to 168 hours after start of treatment | Russel's Viper Venom (RVV) |
| Time from dosing to maximum measured concentration of the analyte in plasma (tmax) | up to 264 hours after start of treatment | — |
| Area under the concentration-time curve of the analyte in plasma (AUC) | up to 264 hours after start of treatment | — |
| Terminal rate constant of the analyte in plasma (λz) | up to 264 hours after start of treatment | — |
| Terminal half-life of the analyte in plasma (t1/2) | up to 264 hours after start of treatment | — |
| Mean residence time of the analyte in the body after oral administration (MRTpo) | up to 264 hours after start of treatment | — |
Outcome results
None listed