Clinical trial NCT02171442: Metabolism and Pharmacokinetics of [14C]-BIBR 953 ZW After Administration of Single Doses of [14C]-BIBR 953 ZW Intravenously or [14C]-BIBR 1048 Oral Solution in Healthy Male Volunteers
Official title: Metabolism and Pharmacokinetics of [14C]-BIBR 953 ZW After Administration of Single Doses of 5 mg [14C]-BIBR 953 ZW Intravenously or 200 mg [14C]-BIBR 1048 Oral Solution in a Group Comparison Design in 12 Healthy Male Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 10
Sex: MALE
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study were to investigate the metabolism and pharmacokinetics of BIBR 1048 MS and BIBR 953 ZW in man.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects as determined by results of screening
* Signed written informed consent from each subject in accordance with the regulatory and legal requirements of the UK
* Age between 30 and 55 years of age
* Body Mass Index (BMI) of between 18.5 and 29.9 kg/m²

Exclusion Criteria:

* Any of the findings from the medical examination (including BP, pulse rate and ECG) deviated from normal or were of clinical relevance
* History of current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders
* History of relevant orthostatic hypotension, fainting spells and blackouts, or volunteers with diseases of the central nervous system (such as epilepsy) or psychiatric disorders
* Diseases of the central nervous system (such as epilepsy) or psychiatric disorders
* Chronic or relevant acute infections
* History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the principal investigator
* History of any bleeding disorder including prolonged or habitual bleeding
* History of other hematologic disease
* History of cerebral bleeding (e.g. after a car accident)
* History of craniocerebral trauma
* Intake of drugs with a long half life (≥ 24h) within 1 month prior to administration
* Any drugs which may have had an influence on the results of the trial within 10 days prior to administration or during the trial
* Any volunteers who had participated in another trial with an investigational drug within 3 months ( 4 months if the drug was a new chemical entity) prior to administration or during the trial
* Exposition to radiation in the previous 12 months (i.e. serial x-rays, CT scan or barium meal)
* Smoker
* Alcohol abuse (\> 60 g/day)
* Drug abuse
* Blood donation within 12 weeks prior to administration or during the trial
* Any excessive physical activities within 5 days prior to administration or during the trial
* Any laboratory value outside the clinically accepted reference range
* History of familial bleeding disorder
* Platelets \> 150 x 10-9 /l
* Unable to defecate at least once a day every two days

Primary outcomes:
measure: Total radioactivity in plasma and whole blood
timeFrame: 168 hours
measure: Total radioactivity in urine and faeces (excretion balance) over 168 h or until < 1% excreted in urine/faeces samples in a 24 h period
timeFrame: over 168 hours or 24 hour period
measure: Concentrations of BIBR 953 ZW in plasma over 168 h, estimation of the extent of gastrointestinal absorption
timeFrame: 168 hours
measure: Concentrations of BIBR 953 ZW in urine
timeFrame: 168 hours
measure: [14C] metabolic pattern and identification of metabolites in urine and if feasible, in plasma and faeces in comparison with various animal species
timeFrame: -12, 0 hours, 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 post dose
Secondary outcomes:
measure: Ratio of radioactivity in blood cells and plasma (CE/CP)
timeFrame: 0.5, 1, 2 ,4 ,8, 24 hours after oral study drug administration, 31min, 1, 2, 4, 8, 24h after start of infusion
measure: Measurement of in vitro plasma protein binding of [14C]-BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: Cmax - Peak (maximum) plasma concentration of BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: tmax - time to reach the peak plasma concentration of BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: t1/2 - Terminal half-life derived from non-compartmental analysis of BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: AUC0-t - area under the plasma concentration vs. time curve from time zero to the time point for the last sample on the pharmacokinetic profile in which total radioactivity or active drug were reliably quantified) BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: AUC0-infinity - Area under the plasma concentration vs. time curve from time zero to infinity - BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: MRT0-inf - the average amount of time a particle remains in a compartment or system, derived when the drug concentration profile is extrapolated to infinity) - BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: MRT0-t - the average amount of time a particle remains in a compartment or system - BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: CL renal - the apparent volume of the central compartment cleared of drug via renal excretion into the urine, per unit time - BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: CLtot - the apparent volume of the central compartment cleared of drug per unit tim after intravenous dosing - BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: CLtot/F - the apparent volume of the central compartment cleared of drug per unit time after extravascular dosing - BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: Vss - apparent volume of distribution at steady state following intravenous administration - BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: Vz/f - Volume of distribution during terminal phase after oral administration - BIBR 953 ZW
timeFrame: Screening, day-1, day 1-day 8
measure: Cmax - Peak (maximum) plasma concentration for total radioactivity
timeFrame: up to day 8
measure: tmax - time to reach the peak plasma concentration for total radioactivity
timeFrame: up to day 8
measure: Occurence of Adverse events
timeFrame: Screening, upt to 10 days after study drug administration
measure: Change from Baseline in physical examination
timeFrame: Screening, 8 to 10 days after study drug administration
measure: Changes from Baseline in vital signs
timeFrame: Screening, 8 to 10 days after study drug administration
measure: Change from Baseline in systolic and diastolic blood pressure
timeFrame: Screening, Day-1, day1, day2, day 8-10 after study drug administration
measure: Change from Baseline in Pulse rate
timeFrame: Screening, Day-1, day1, day2, day 8-10 after study drug administration
measure: Change from Baseline in 12-lead electrocardiogram (ECG)
timeFrame: Screening, Day-1, day1, day2, day 8-10 after study drug administration
measure: Change from Baseline in clinical laboratory tests (hematology, clinical chemistry and urinanalysis)
timeFrame: Screening, day-1, day1, day2, day3, day 8-10 after study drug administration
measure: Changes from baseline in activated partial thromboplastin time - aPTT
timeFrame: Screening, 1, 2, 24, 48 and 168 hours post dose administration
measure: Changes from baseline in coagulation parameter INR - international normalized ratio prothrombin time
timeFrame: Screening, 1, 2, 24, 48 and 168 hours post dose administration
Other outcomes:
Locations:
Study officials:
References: