The primary objectives of the study are: * To determine the absolute bioavailability of SK-1404 * To assess the mass balance recovery after a single oral (PO) dose of carbon-14 (14C)-SK-1404 * To provide plasma, urine and faecal samples for metabolite profiling and structural identification The secondary objectives of the study are: * To determine the routes and rates of elimination of \[14C\]-SK-1404 * To identify the chemical structure of each metabolite with an exposure (AUC) of more than 10% of circulating total radioactivity * To explore the intravenous (IV) pharmacokinetics (PK) of \[14C\]-SK-1404 * To further explore the PO PK of SK-1404 * To provide additional safety and tolerability information for SK-1404
This is a single-centre, 2-part, open-label, non-randomised, sequential, single dose study in healthy male subjects. It is planned to enrol a single cohort of 6 healthy male subjects who will participate in Parts 1 and Part 2 of the study. In Part 1, each subject will receive a single PO dose of SK-1404 followed by an IV microtracer dose of \[14C\]-SK-1404. In Part 2, each subject will receive a single PO dose of \[14C\]-SK-1404.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
6
In Part 1, each subject will receive a single PO dose of SK-1404 followed by an IV microtracer dose of \[14C\]-SK-1404.
Quotient Clinical
Ruddington, Nottingham, United Kingdom
Absolute bioavailability (F) calculated with the AUC values of IV administration in Part 1 and PO administration in Part 2
Time frame: Predose to 96hr
Mass balance recovery of total radioactivity in urine, faeces and all excreta
Amount excreted (Ae), and Ae as a percentage of the administered dose (%Ae), cumulative recovery (Cum Ae) and cumulative recovery expressed as a percentage of the dose (Cum %Ae)
Time frame: Predose to 168hr
Number and structural identification of known and unknown metabolites of SK-1404 in the plasma, urine and faeces samples
Time frame: Predose to 168hr
Ae total radioactivity in plasma by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
Time frame: Predose to 168hr
%Ae total radioactivity in plasma by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
Time frame: Predose to 168hr
Cum Ae (total) for urine by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
Time frame: Predose to 168hr
Cum %Ae (total) for urine by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
Time frame: Predose to 168hr
Cum Ae (total) for faeces by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
Time frame: Predose to 168hr
Cum %Ae (total) for faeces by metabolite profiling and structural identification to estimate the routes and rates of elimination of [14C]-SK-1404
Time frame: Predose to 168hr
Number and structural identification of unknown metabolites of SK-1404 with an AUC of more than 10% of circulating total radioactivity
Time frame: Predose to 168hr
The peak plasma concentration (Cmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The time from dosing at which Cmax was apparent (Tmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The elapsed time from dosing at which the analyte was first quantifiable in a concentration vs time profile (Tlag) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The area under the concentration-time curve from dosing to the last measurable concentration (AUC(0-last)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The area under the concentration-time curve from dosing extrapolated to infinity (AUC(0-inf)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The percentage of AUC(0-inf) extrapolated beyond the last measured time point (AUC%extrap) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The terminal elimination rate constant calculated from the slope of the apparent elimination phase (lambda-z) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The apparent terminal elimination half-life (T1/2) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The apparent total clearance (CL/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The apparent volume of distribution (Vd) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The apparent volume of distribution (Vss) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The mean residence time (MRT) of SK-1404F and its active metabolites M-1, M-7 and M-9) after IV SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 96hr
The peak plasma concentration (Cmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The time from dosing at which Cmax was apparent (Tmax) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The elapsed time from dosing at which the analyte was first quantifiable in a concentration vs time profile (Tlag) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The area under the concentration-time curve from dosing to the last measurable concentration (AUC(0-last)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The area under the concentration-time curve from dosing extrapolated to infinity (AUC(0-inf)) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The percentage of AUC(0-inf) extrapolated beyond the last measured time point (AUC%extrap) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The terminal elimination rate constant calculated from the slope of the apparent elimination phase (lambda-z) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The apparent terminal elimination half-life (T1/2) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The absolute bioavailability (F, PO vs IV from Part 1) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The apparent total clearance (CL/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The apparent volume of distribution (Vd/F) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
The mean residence time (MRT) of SK-1404F and its active metabolites M-1, M-7 and M-9) after PO SK-1404
Metabolite:parent ratios will be calculated for SK-1404F, M-1, M-7 and M-9
Time frame: Predose to 168hr
To collect further information about the safety and tolerability of IMP
By assessing physical examination, safety laboratory tests, vital signs, electrocardiograms (ECGs) and AEs.
Time frame: Predose to 168hr
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