This Phase I ADME study will be conducted to evaluate the pharmacokinetics of benznidazole.
This will be a single-site, open-label, non-randomized, single oral dose absorption, metabolism and excretion study in healthy male subjects. Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to dosing on Day 1. Subjects will be admitted into the Clinical Research Unit (CRU) on Day -1. Subjects will be confined to the CRU until at least Day 11 (240 hours postdose), and will be discharged from the CRU on Day 11 if all the following discharge criteria are met: \>90% mass balance recovery; OR plasma/blood radioactivity levels below the limit of quantitation for 2 consecutive collections; and \<1% of the total radioactive dose recovered in combined excreta (urine and faeces) in 2 consecutive 24-hour periods. If these criteria are not met by Day 11, subjects will remain in the CRU until all discharge criteria are met up to a maximum of Day 15 to continue 24-hour blood, urine and faeces collections for the analysis of total radioactivity, unless otherwise agreed upon by the Sponsor and Investigator. If the discharge criteria are not met by Day 15, subjects may be asked to collect 24-hour excreta samples on up to 2 further occasions on a nonresidential basis to allow extrapolation of urinary and faecal excretion. If needed, the 2 additional 24-hour nonresidential collections will occur on Day 21 (±1 day) and Day 28 (±1 day). If on the second occasion the subject has still not met the desired criterion, then the subject will be discharged from the study, per Investigator and Sponsor decision. Pharmacokinetic samples and radioanalytical samples will be obtained through at least 240 hours postdose, and possibly up to 4 weeks postdose (radioanalytical samples only), in case of not meeting discharge criteria. Samples for metabolite profiling/identification will be obtained through 240 hours postdose.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
6
A single dose level of 100 mg; 200 μCi (7.4 MBq)
Covance
Leeds, United Kingdom
Cmax of BNZ in plasma
maximum observed concentration (Cmax) in plasma
Time frame: Days 1-29
Mass balance of [14C]-BNZ
Mass balance of \[14C\]-BNZ in urine and faeces
Time frame: Days 1-29
Chemical structure of [14C]-BNZ metabolites
Characterization of the chemical structure and identification of metabolites of \[14C\]-BNZ in plasma, urine, and faeces
Time frame: Days 1-29
tmax of BNZ in plasma
time to maximum concentration (tmax) in plasma
Time frame: Days 1-29
AUC0-t of BNZ in plasma
area under the concentration-time curve (AUC) from hour zero to the last measurable concentration (AUC0-t) in plasma
Time frame: Days 1-29
AUC0-∞ of BNZ in plasma
AUC from time zero to infinity (AUC0-∞) in plasma
Time frame: Days 1-29
% AUC extrap of BNZ in plasma
percentage extrapolation (% AUCextrap) in plasma
Time frame: Days 1-29
t1/2 of BNZ in plasma
apparent terminal elimination half-life (t1/2) in plasma
Time frame: Days 1-29
CL/Fof BNZ in plasma
apparent oral clearance (CL/F) in plasma
Time frame: Days 1-29
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Vz/F of BNZ in plasma
volume of distribution during the elimination phase for BNZ (Vz/F) in plasma
Time frame: Days 1-29
Cmax of [14C]-BNZ in plasma
maximum observed concentration (Cmax) in plasma
Time frame: Days 1-29
tmax of [14C]-BNZ in plasma
time to maximum concentration (tmax) in plasma
Time frame: Days 1-29
AUC0-t of [14C]-BNZ in plasma
area under the concentration-time curve (AUC) from hour zero to the last measurable concentration (AUC0-t) in plasma
Time frame: Days 1-29
AUC0-∞ of [14C]-BNZ in plasma
AUC from time zero to infinity (AUC0-∞) in plasma
Time frame: Days 1-29
% AUC extrap of [14C]-BNZ in plasma
percentage extrapolation (% AUCextrap) in plasma
Time frame: Days 1-29
t1/2 of [14C]-BNZ in plasma
apparent terminal elimination half-life (t1/2) in plasma
Time frame: Days 1-29
Cmax of [14C]-BNZ in whole blood
maximum observed concentration (Cmax) in whole blood
Time frame: Days 1-29
tmax of [14C]-BNZ in whole blood
time to maximum concentration (tmax) in whole blood
Time frame: Days 1-29
AUC0-t of [14C]-BNZ in whole blood
area under the concentration-time curve (AUC) from hour zero to the last measurable concentration (AUC0-t) in whole blood
Time frame: Days 1-29
AUC0-∞ of [14C]-BNZ in whole blood
AUC from time zero to infinity (AUC0-∞) in whole blood
Time frame: Days 1-29
% AUCextrap of [14C]-BNZ in whole blood
percentage extrapolation (% AUCextrap) in whole blood
Time frame: Days 1-29
t1/2 of [14C]-BNZ in whole blood
apparent terminal elimination half-life (t1/2) in whole blood
Time frame: Days 1-29
Total radioactivity AUC ratio
Total radioactivity AUC ratio (blood/plasma)
Time frame: Days 1-29
The incidence and severity of Adverse Events (AEs)
The incidence of AEs will be presented by severity and by association with the study drug as determined by the Investigator (or designee).
Time frame: Days 1-29
The incidence of laboratory abnormalities (haematology)
The incidence of laboratory abnormalities will be measured based on haematology test result.
Time frame: Days 1-29
The incidence of laboratory abnormalities (clinical chemistry)
The incidence of laboratory abnormalities will be measured based on clinical chemistry test result.
Time frame: Days 1-29
The incidence of laboratory abnormalities (urinalysis)
The incidence of laboratory abnormalities will be measured based on urinalysis test result.
Time frame: Days 1-29
Measurement of QT interval (QTcB)
Measure of 12-lead electrocardiogram (ECG); QT interval calculated using the Bazett correction (QTcB) in millisecond
Time frame: Days 1-29
Measurement of QT interval (QTcF)
Measure of 12-lead electrocardiogram (ECG); QT interval calculated using the Fridericia correction (QTcF) in millisecond
Time frame: Days 1-29
Measurement of PR intervals
Measure of 12-lead electrocardiogram (ECG); PR intervals in millisecond.
Time frame: Days 1-29
Measurement of QT intervals
Measure of 12-lead electrocardiogram (ECG); QT intervals in millisecond
Time frame: Days 1-29
Measurement of QRS duration
Measure of 12-lead electrocardiogram (ECG); QRS duration in millisecond
Time frame: Days 1-29
Measurement of RR
Measure of 12-lead electrocardiogram (ECG); RR in millisecond
Time frame: Days 1-29
Measurement of heart rate
Measure of 12-lead electrocardiogram (ECG); heart rate in beats per minute (BPM)
Time frame: Days 1-29
Measurement of blood pressure
Measure of supine systolic and diastolic blood pressure ( both in mmHg)
Time frame: Days 1-29
Measurement of Physical Examination
Weight (in kilograms) and Height (in centimeters) will be measured
Time frame: Days 1-29
Measurement of supine pulse rate
supine pulse rate (in beats/minute)
Time frame: Days 1-29
Measurement body temperature
oral body temperature (in Degree Celsius)
Time frame: Days 1-29
Measurement of Weight
weight (in kilograms)
Time frame: Days 1-29
Measurement of Height
height (in centimeters) w
Time frame: Days 1-29