Clinical trial NCT02171689: Metabolism and Pharmacokinetics of [14C]- BIBW 2992 MA2 in Healthy Male Volunteers
Official title: Metabolism and Pharmacokinetics of [14C]- BIBW 2992 MA2 After Administration of Single Doses of 15 mg [14C]- BIBW 2992 MA2 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: 2014-06-24
Enrollment: 8
Sex: MALE
Minimum age (years): 35
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of the study was to investigate the metabolism and pharmacokinetics of BIBW 2992 MA2 after a single oral dose of \[14C\]-radiolabelled BIBW 2992 MA2 in healthy male volunteers. Metabolites in human plasma and excretions were measured, the structures of the metabolites analysed and compared with metabolites in animals. In addition, the mass-balance of excretion, the protein binding of \[14C\]-radioactivity, the plasma concentrations of BIBW 2992 MA2, and the \[14C\]-radioactivity in blood cells, plasma, urine and faeces were measured. The safety and tolerability of BIBW 2992 were also investigated.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects as determined by results of screening
* Signed written informed consent in accordance with Good Clinical Practice and local legislation
* Age ≥35 and ≤60 years
* Body Mass Index ≥18.5 kg/m2 and ≤29.9 kg/m2

Exclusion Criteria:

* Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
* History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders
* History of any major surgery within the last four weeks before participation in this study or any bone fracture within the last two months
* History of orthostatic hypotension, fainting spells and blackouts
* 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 investigator
* Intake of drugs with a long half-life (\> 24 hours) within 1 month prior to administration
* Planned use of any drugs which might influence the results of the trial within 10 days prior to administration or during the trial
* Participation in another trial with an investigational drug within 2 months prior to administration or during trial
* Smoker (\> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days
* Alcohol abuse (\> 60 g/day)
* Drug abuse
* Blood donation within 1 month prior to administration or during the trial
* Excessive physical activities within 5 days prior to administration or during the trial
* Any laboratory value outside the reference range, unless considered to lack clinical reference
* 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 (CBlood cells/Cplasma ratio of [14C]-radioactivity)
timeFrame: up to 96 hours after drug administration
measure: [14C]-radioactivity in urine and faeces (excretion mass balance)
timeFrame: up to 120 hours after drug administration
measure: Measurement of the plasma protein binding of total [14C]-radioactivity
timeFrame: up to 96 hours after drug administration
measure: Concentrations of the analyte in plasma, urine, and faeces
timeFrame: up to 96 hours after drug administration
measure: Cmax (maximum observed concentration of the analyte in plasma)
timeFrame: up to 96 hours after drug administration
measure: tmax (time from dosing to peak concentration (Cmax))
timeFrame: up to 96 hours after drug administration
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: up to 96 hours after drug administration
measure: λz (terminal rate constant of the analyte in plasma)
timeFrame: up to 96 hours after drug administration
measure: AUC (area under the concentration-time curve of the analyte in plasma) for different time points
timeFrame: up to 96 hours after drug administration
measure: MRTpo (mean residence time of the analyte molecules in the body after oral administration)
timeFrame: up to 96 hours after drug administration
measure: CL/F (total clearance of the analyte in plasma following extravascular administration)
timeFrame: up to 96 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase following extravascular administration)
timeFrame: up to 96 hours after drug administration
measure: fe0-tz (fraction of analyte eliminated in urine or faeces from 0 to the limit of the last quantifiable data point)
timeFrame: up to 120 hours after drug administration
measure: Aet0-tz (amount of analyte eliminated in urine or faeces from 0 the limit of the last quantifiable data point)
timeFrame: up to 120 hours after drug administration
measure: Plasma concentration time profiles of the analyte
timeFrame: up to 96 hours after drug administration
measure: Plasma concentration-time profiles of total radioactivity in whole blood and plasma
timeFrame: up to 96 hours after drug administration
measure: [14C]-metabolic profile and identification of metabolites in urine, faeces, blood cells and plasma
timeFrame: up to 120 hours after drug administration
Secondary outcomes:
measure: Number of patients with clinically relevant changes in vital signs (Pulse rate (PR), systolic and diastolic blood pressure (BP))
timeFrame: Baseline, day 2, within 14 days after study drug administration
measure: Number of patients with clinically relevant changes in ECG (electrocardiogram)
timeFrame: Baseline, day 2, within 14 days after study drug administration
measure: Number of patients with clinically relevant changes in laboratory parameters
timeFrame: Baseline, day 2, within 14 days after study drug administration
measure: Number of patients with adverse events
timeFrame: up to 27 days
measure: Assessment of tolerability on a 4-point scale
timeFrame: within 14 days after study drug administration
Other outcomes:
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