Clinical trial NCT02182154: Metabolism and Pharmacokinetics of [14C]-BIBF 1120 in Healthy Male Volunteers
Official title: Metabolism and Pharmacokinetics of [14C]-BIBF 1120 After Administration of Single Doses of 100 mg [14C]-BIBF 1120 Oral Solution in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 8
Sex: MALE
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the metabolic profile,

to obtain the mass balance after oral administration,

to determine the concentration of \[14C\]-radioactivity in blood cells, plasma, urine and faeces,

to determine BIBF 1120 and BIBF 1202 concentrations in plasma, urine, and faeces, if feasible,

to determine the protein binding of \[14C\]-radioactivity,

to determine the pharmacokinetics of BIBF 1120, BIBF 1202 and total radioactivity after a single oral administration of \[14C\]-BIBF 1120 in healthy volunteers


Eligibility criteria: Inclusion Criteria:

1. Healthy male subjects as determined by results of screening
2. Signed written informed consent in accordance with GCP and local legislation
3. Age ≥21 and ≤55 years
4. Body Mass Index ≥18.5 kg/m2 and ≤29.9 kg/m2

Exclusion Criteria:

1. Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
2. History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders
3. History of any major surgery within the last four weeks before participation in this study or any bone fracture within the last two months
4. History of orthostatic hypotension, fainting spells and blackouts
5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders
6. Chronic or relevant acute infections
7. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
8. History of any bleeding disorder including prolonged or habitual bleeding, other haematologic disease or cerebral bleeding (e.g. after a car accident) or commotio cerebri
9. Intake of drugs with a long half-life (\> 24 hours) within 1 month prior to administration
10. Planned use of any drugs which might influence the results of the trial within 10 days prior to administration or during the trial
11. Participation in another trial with an investigational drug within 2 months prior to administration or during trial
12. Smoker (\> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days
13. Alcohol abuse (\> 60 g/day)
14. Drug abuse
15. Blood donation within 1 month prior to administration or during the trial
16. Excessive physical activities within 5 days prior to administration or during the trial
17. Any laboratory value outside the reference range, unless considered to lack clinical reference
18. Female gender
19. Male subjects must agree to minimize the risk of female partners becoming pregnant from the dosing day until 3 months after the completion of the study. Acceptable methods of contraception for male volunteers include a vasectomy no less than 3 months prior to dosing, barrier contraception or a medically accepted contraceptive method. For female partners of male volunteers, acceptable methods of contraception include intra-uterine device, tubal ligation, hormonal contraceptive since at least two months and diaphragm with spermicide

Primary outcomes:
measure: [14C]-radioactivity in plasma and whole blood (C Blood cells/C plasma ratio of [14C]-radioactivity)
timeFrame: Up to 96 h after drug administration
measure: [14C]-radioactivity in urine
timeFrame: Up to 120 h after drug administration
measure: Measurement of the plasma protein binding of total [14C]-radioactivity in human plasma samples ex vivo
timeFrame: Up to 96 h after drug administration
measure: Maximum observed concentration of the analyte in plasma (Cmax)
timeFrame: Up to 96 h after drug administration
measure: Plasma concentration-time profiles of total radioactivity in whole blood and plasma
timeFrame: Up to 96 h after drug administration
measure: [14C]-metabolic profile and identification of metabolites in urine, in comparison with various animal species
timeFrame: Up to 120 h after drug aministration
measure: [14C]-radioactivity in faeces
timeFrame: up to 120 h after administration
measure: [14C]-metabolic profile and identification of metabolites in faeces, in comparison with various animal species
timeFrame: Up to 120 h after drug aministration
measure: [14C]-metabolic profile and identification of metabolites in plasma, in comparison with various animal species
timeFrame: Up to 96 h after drug aministration
measure: Time from dosing to peak concentration (tmax)
timeFrame: Up to 96 h after drug administration
measure: Terminal half-life of the analyte in plasma (t1/2)
timeFrame: Up to 96 h after drug administration
measure: Terminal rate constant of the analyte in plasma (λz)
timeFrame: Up to 96 h after drug administration
measure: Area under the concentration-time curve of the analyte in plasma from zero time to 24 hours (AUC0-24)
timeFrame: Up to 24 h after drug administration
measure: Area under the concentration-time curve of the analyte in plasma from zero time to the time of the last quantifiable drug concentration (AUC0-tz)
timeFrame: Up to 96 h after drug administration
measure: Area under the concentration-time curve of the analyte in plasma from zero time to infinity (AUC0-∞)
timeFrame: Up to 96 h after drug administration
measure: Mean residence time of the analyte molecules in the body after oral administration (MRTpo)
timeFrame: Up to 96 h after drug administration
measure: Total clearance of the analyte in plasma following extravascular administration (CL/F)
timeFrame: Up to 96 h after drug administration
measure: Apparent volume of distribution during the terminal phase λz following extravascular administration (Vz/F)
timeFrame: Up to 96 h after drug administration
measure: Fraction of analyte eliminated in urine from 0 to the limit of the last quantifiable data point (fe0-tz)
timeFrame: Up to 96 h after drug administration
measure: Fraction of analyte eliminated in faeces from 0 to the limit of the last quantifiable data point (fe faeces,0-tz)
timeFrame: Up to 96 h after drug administration
measure: Amount of analyte that was eliminated in faeces from 0 to the limit of the last quantifiable data point (Ae faeces,0-tz)
timeFrame: Up to 96 h after drug administration
measure: Amount of analyte that was eliminated in urine from 0 to the limit of the last quantifiable data point (Ae0-tz)
timeFrame: Up to 96 h after drug administration
Secondary outcomes:
measure: Change from baseline in vital signs
timeFrame: Baseline, day 14 after drug administration
measure: Change from baseline in routine laboratory
timeFrame: Baseline, day 14 after drug aministration
measure: Number of participants with adverse events
timeFrame: Up to day 14 after drug aministration
measure: Change from baseline in electrocardiogram
timeFrame: Baseline, day 14 after drug aministration
measure: Assessment of tolerability by investigator according a 4 point scale
timeFrame: Day 14 after drug administration
Other outcomes:
Locations:
Study officials:
References: