The purpose of this study is to evaluate the safety and tolerability of single and multiple oral doses of ESN364 in healthy Japanese male and pre- and post-menopausal female subjects. This study will also evaluate the pharmacokinetics (PK) of ESN364 and its metabolite, and the pharmacodynamics (PD) of ESN364 after single and multiple oral doses administration in healthy Japanese male and pre- and post-menopausal female subjects.
This study consists of two parts. Part 1; Single Dose (SD) and Part 2; Single and Multiple Dose (SD and MD).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
44
Site JP00001
Fukuoka, Japan
Safety assessed by incidence of adverse events (AEs) in Part 1
AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA).
Time frame: Up to Day 12 in Part 1
Safety assessed by incidence of AEs in Part 2
AEs will be coded using MedDRA.
Time frame: Up to Day 24 in Part 2
Safety assessed by vital signs: Body temperature in Part 1
To assess vital signs as a criterion of safety variables.
Time frame: Up to day 12 in Part 1
Safety assessed by vital signs: Body temperature in Part 2
To assess vital signs as a criterion of safety variables.
Time frame: Up to Day 24 in Part 2
Safety assessed by vital signs: Blood pressure in Part 1
To assess vital signs as a criterion of safety variables.
Time frame: Up to Day 12 in Part 1
Safety assessed by vital signs: Blood pressure in Part 2
To assess vital signs as a criterion of safety variables.
Time frame: Up to Day 24 in Part 2
Safety assessed by vital signs: Pulse rate in Part 1
To assess vital signs as a criterion of safety variables.
Time frame: Up to Day 12 in Part 1
Safety assessed by vital signs: Pulse rate in Part 2
To assess vital signs as a criterion of safety variables.
Time frame: Up to Day 24 in Part 2
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Safety assessed by laboratory test: Hematology in Part 1
To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.
Time frame: Up to Day 12 in Part 1
Safety assessed by laboratory test: Hematology in Part 2
To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.
Time frame: Up to Day 24 in Part 2
Safety assessed by laboratory test: Biochemistry in Part 1
To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.
Time frame: Up to Day 12 in Part 1
Safety assessed by laboratory test: Biochemistry in Part 2
To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.
Time frame: Up to Day 24 in Part 2
Safety assessed by laboratory test: Urinalysis in Part 1
To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.
Time frame: Up to Day 12 in Part 1
Safety assessed by laboratory test: Urinalysis in Part 2
To assess laboratory values as a criterion of safety variables. Potentially clinically significant laboratory values will be reported as AEs.
Time frame: Up to Day 24 in Part 2
Safety assessed by standard 12-lead electrocardiogram (ECG) in Part 1
Subjects should keep rest for 5 minutes before evaluation. Any clinically significant adverse changes on the ECG will be reported as AEs.
Time frame: Up to Day 12 in Part 1
Safety assessed by standard ECG in Part 2
Subjects should keep rest for 5 minutes before evaluation. Any clinically significant adverse changes on the ECG will be reported as AEs.
Time frame: Up to Day 24 in Part 2
Safety assessed by ECG parameters: Heart rate in Part 1
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing in Part 1
Safety assessed by ECG parameters: Heart rate in Part 2
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing on Day 10 in multiple dose (MD) of Part 2
Safety assessed by ECG parameters: QT interval in Part 1
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing in Part 1
Safety assessed by ECG parameters: QT interval in Part 2
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing on Day 10 in MD of Part 2
Safety assessed by ECG parameters: RR interval in Part 1
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing in Part 1
Safety assessed by ECG parameters: RR interval in Part 2
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing on Day 10 in MD of Part 2
Safety assessed by ECG parameters: PR interval in Part 1
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing in Part 1
Safety assessed by ECG parameters: PR interval in Part 2
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing on Day 10 in MD of Part 2
Safety assessed by ECG parameters: QRS interval in Part 1
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing in Part 1
Safety assessed by ECG parameters: QRS interval in Part 2
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing on Day 10 in MD of Part 2
Safety assessed by ECG parameters: QTc interval corrected by Fridericia method (QTcF) in Part 1
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing in Part 1
Safety assessed by ECG parameters: QTcF in Part 2
To assess ECG parameters as a criterion of safety variables.
Time frame: Up to 24 hr after dosing on Day 10 in MD of Part 2
Safety assessed by body weight in Part 1
To assess body weight as a criterion of safety variables
Time frame: Up to Day 3 in Part 1
Safety assessed by body weight in Part 2
To assess body weight as a criterion of safety variables
Time frame: Up to Day 15 in Part 2
Safety assessed by menstrual cycle in pre-menopausal females
To assess menstrual cycle as a criterion of safety variables
Time frame: Up to an average of two weeks after last dosing
Pharmacokinetics (PK) parameter for ESN364 and its metabolite: Area under the concentration-time curve (AUC) from the time of dosing to time 24 h (AUC24) in plasma
To assess the PK of ESN364 and its metabolite in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2
PK parameter for ESN364 and its metabolite: AUC from the time of dosing extrapolated to time infinity (AUCinf) in plasma
To assess the PK of ESN364 and its metabolite4 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2
PK parameter for ESN364 and its metabolite: Percentage of AUCinf (AUCinf(%extrap)) in plasma
To assess the PK of ESN364 and its metabolite in Part 1.
Time frame: Up to 48 hr after dosing in Part 1
PK parameter for ESN364 and its metabolite: AUC from the time of dosing to the last measurable concentration (AUClast) in plasma
To assess the PK of ESN364 and its metabolite in Part 1.
Time frame: Up to 48 hr after dosing in Part 1
PK parameter for ESN364 and its metabolite: Maximum concentration (Cmax) in plasma
To assess the PK of ESN364 and its metabolite in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: Apparent total clearance after extra-vascular dosing (CL/F) in plasma
To assess the PK of ESN364 and its metabolite in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: Time point prior to the time point corresponding to the first measurable (non-zero) concentration (tlag) in plasma
To assess the PK of ESN364 and its metabolite in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: Time of the maximum concentration： (tmax) in plasma
To assess the PK of ESN364 and its metabolite in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: Terminal elimination half-life (t1/2) in plasma
To assess the PK of ESN364 and its metabolite in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: volume of distribution during the terminal elimination phase after extra-vascular dosing (Vz/F) in plasma
To assess the PK of ESN364 and its metabolite in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 metabolite: Metabolite to parent ratio (MPR) in plasma
To assess the PK of ESN364 metabolite in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: AUC from the time of dosing to the start of the next dosing interval (AUCtau) in plasma
To assess the PK of ESN364 and its metabolite in Part 2.
Time frame: Up to 48 hr after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: Peak-trough ratio (PTR) in plasma
To assess the PK of ESN364 and its metabolite in Part 2.
Time frame: Up to 48 hr after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: Accumulation ratio calculated using AUC (Rac(AUC)) in plasma
To assess the PK of ESN364 and its metabolite in Part 2.
Time frame: Up to 48 hr after dosing on Day 10 in MD part of Part 2
PK parameter for ESN364 and its metabolite: Concentration immediately prior to dosing at multiple dosing (Ctrough) in plasma
To assess the PK of ESN364 and its metabolite in Part 2.
Time frame: Before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2
Pharmacodynamic (PD) endpoint for ESN364: Luteinizing hormone (LH) level in plasma
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUC12 for LH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC24 for LH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC48 for LH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: Cmin for LH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: tmin for LH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUC from the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) for LH level
To assess the PD of ESN364 in Part 2.
Time frame: Before dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: Cpredose for LH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Before dosing in Part 1 and before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2
PD endpoint for ESN364: Follicle stimulating hormone (FSH) level in plasma
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUC12 for FSH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC24 for FSH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC48 for FSH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: Cmin for FSH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: tmin for FSH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUCtau for FSH level
To assess the PD of ESN364 in Part 2.
Time frame: Before dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: Cpredose for FSH level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Before dosing in Part 1 and before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2
PD endpoint for ESN364: Sex hormone binding globulin (SHBG) level in plasma
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUC12 for SHBG level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC24 for SHBG level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC48 for SHBG level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: Cmin for SHBG level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: tmin for SHBG level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUCtau for SHBG level
To assess the PD of ESN364 in Part 2.
Time frame: Before dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: Cpredose for SHBG level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Before dosing in Part 1 and before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2
PD endpoint for ESN364: Total testosterone (TT) level in plasma
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUC24 for TT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC12 for TT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC48 for TT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: Cmin for TT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: tmin for TT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUCtau for TT level
To assess the PD of ESN364 in Part 2.
Time frame: Before dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: Cpredose for TT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Before dosing in Part 1 and before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2
PD endpoint for ESN364: Free testosterone (FT) level in plasma
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUC12 for FT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC24 for FT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: AUC48 for FT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1 and after first dosing in Part 2.
PD endpoint for ESN364: Cmin for FT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: tmin for FT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Up to 48 hr after dosing in Part 1, after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUCtau for FT level
To assess the PD of ESN364 in Part 2.
Time frame: Before dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: Cpredose for FT level
To assess the PD of ESN364 in Part 1 and Part 2.
Time frame: Before dosing in Part 1 and before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2
PD endpoint for ESN364: Estradiol (E) level in plasma
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUC12 for E level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2.
PD endpoint for ESN364: AUC24 for E level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2.
PD endpoint for ESN364: AUC48 for E level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2.
PD endpoint for ESN364: Cmin for E level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: tmin for E level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUCtau for E level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Before dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: Cpredose for E level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2
PD endpoint for ESN364: Progesterone (P) level in plasma
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUC12 for P level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2.
PD endpoint for ESN364: AUC24 for P level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2.
PD endpoint for ESN364: AUC48 for P level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2.
PD endpoint for ESN364: Cmin for P level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: tmin for P level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Up to 48 hr after first dosing in Part 2 and after dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: AUCtau for P level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Before dosing on Day 10 in MD part of Part 2
PD endpoint for ESN364: Cpredose for P level
To assess the PD of ESN364 in female subjects in Part 2.
Time frame: Before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2