Resminostat is a potent, orally available inhibitor of Class I, IIb and IV histone deacetylases (HDACs), including a pronounced activity against HDAC6. Resminostat targets epigenetic changes observed in tumour cells and has the potential to provide significant benefit to patients with advanced malignancies by inhibiting tumour progression and metastasis or even inducing tumour regression. This will be a Phase 1, open-label, non-randomized, single dose study of the absorption, metabolism, excretion of \[14C\] resminostat following a single oral dose in healthy male participants. The purpose of this study is to determine the absorption, metabolism, and excretion (AME) of \[14C\] resminostat and to characterize and determine the metabolites present in plasma, urine, and, where possible, faeces in healthy male participants following a single oral administration. Knowledge of the metabolism and excretion of parent drug and its metabolites is useful for evaluating the Metabolites in Safety Testing requirements elucidated in the International Conference on Harmonisation (ICH) M3, and the likelihood of effects of renal or hepatic impairment on the disposition of resminostat, and the likelihood for drug-drug interactions with resminostat. The results from this study may guide future study designs using special populations or evaluating the potential for drug-drug interactions.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
1 single dose of 400 mg \[14C\]-resminostat
Covance Clinical research Unit Ltd.
Leeds, United Kingdom
AUC0-tlast
AUC from time zero to the last quantifiable concentration derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
AUC0-∞
AUC from time zero extrapolated to infinity derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Cmax
maximum observed concentration derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
tmax
time to reach Cmax derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
tlag
time to the first quantifiable concentration in plasma derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
λz
terminal elimination rate constant derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
t1/2
apparent terminal elimination half-life derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
CL/F
apparent total clearance derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Vz/F
apparent volume of distribution derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
AUC0-∞ Plasma resminostat/Total Radioactivity Ratio
AUC0-∞ of plasma resminostat relative to AUC0-∞ of plasma total radioactivity derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
AUC0-∞ Blood/Plasma Ratio
AUC0-∞ of whole blood total radioactivity to AUC0-∞ of plasma total radioactivity derived from the whole blood and plasma concentration-time profiles following oral administration of \[14C\]-resminostat
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Aeu
amount excreted in urine derived from urine collections at each sampling interval
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
cumulative Aeu
cumulative amount excreted in urine derived from urine collections at each sampling interval
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
feu
percentage excreted in urine derived from urine collections at each sampling interval
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
cumulative feu
cumulative percentage excreted in urine derived from urine collections at each sampling interval
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Aef
amount excreted in feces derived from feces collections at each sampling interval
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
cumulative Aef
cumulative amount excreted in feces derived from feces collections at each sampling interval
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
fef
percentage excreted in feces derived from feces collections at each sampling interval
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
cumulative fef.
cumulative percentage excreted in feces derived from feces collections at each sampling interval
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Safety and Tolerability
AE reporting including relatedness and severity
Time frame: from study drug intake until 28 days after study drug administration
Heart rhythm
ECG analysis by 12-lead ECG
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Ventricular rate
ECG analysis by 12-lead ECG
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
PR-interval (synonymous: PQ interval)
ECG analysis by 12-lead ECG
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
QRS complex
ECG analysis by 12-lead ECG
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
QT interval
ECG analysis by 12-lead ECG
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
QTcF interval
ECG analysis by 12-lead ECG
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Vital Signs (Body Temperature)
Body temperature will be measured after a 5 minute rest in supine position
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Vital Signs (Blood pressure)
Systolic and diastolic blood pressure will be measured after a 5 minute rest in supine position
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
Physical Examination
A full physical examination covering at least head, eyes, ears, nose and throat, lungs, heart, neurological status, abdomen, extremities, skin, and lymph nodes
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
metabolic profiles of resminostat
identification and quantification of metabolites in serum and urin samples by HPLC
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat
identification and quantification of resminostat metabolites
identification and quantification of metabolites in serum and urin samples by HPLC
Time frame: From day -1 until maximum 15 days after single dose of [14C]-resminostat