A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ESN364 in Healthy Japanese Male and Pre- and Post-menopausal Female Subjects

Study Overview
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Brief Summary
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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.

Detailed Description
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This study consists of two parts. Part 1; Single Dose (SD) and Part 2; Single and Multiple Dose (SD and MD).

Official Title
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Phase 1 Study of ESN364 - Placebo-controlled, Single and Multiple Oral Dose Study in Healthy Japanese Male and Healthy Japanese Pre- and Postmenopausal Female Subjects -

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: ESN364
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subject between 20 to < 45 years of age, or female subject between 20 to < 65 years of age. Body weight at screening: ≥ 50.0 kg and < 80.0 kg for male, ≥ 40.0 kg and < 70.0 kg for female. Body mass index (BMI) at screening: range of ≥ 17.6 kg/m2 and < 26.4 kg/m2 [BMI = Body weight (kg) ÷ {Body height (m)2}]. Exclusion Criteria: Subjects who participated or are scheduled to participate in any clinical trials or post-marketing studies within 84 days prior to screening. Subject has had previous exposure with ESN364. Subject has any clinically significant history of allergic conditions prior to study drug administration. Subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy. Subject has contracted pyretic or symptomatic viral, bacterial, or fungal infection within 7 days prior to hospital admission. Any deviation from the normal range of blood pressure, pulse, body temperature, or routine 12-lead ECG at screening or on the day of hospital admission. Subjects who has any significantly abnormal results of laboratory tests at screening or on the day of hospital admission. Subjects who are positive for any of urinary drug abuse test or serology test at screening. Subject took a drug or underwent therapy within 2 weeks prior to hospital admission. Subjects used a drug or underwent therapy that affects sex hormones within 3 months prior to hospital admission. Subjects who had bilateral orchiectomy. Subject has used any inducer of metabolism in the 3 months prior to hospital admission. Subject has a history of smoking more than 10 cigarettes per day within 3 months prior to screening test. Subject consumes, on average, more than approximately 500 mg/day of caffeine Subject has a history of consuming more than 30 units of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism or drug/chemical/ substance abuse within past 2 years prior to screening. Subjects who conducted or is scheduled to conduct any blood donation or blood drawing.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESN364 dose-1 group in Part 1<br>Healthy male subjects will receive a single dose of ESN364. | Drug: ESN364<br>* ESN364 will be administered orally.<br>|
| Experimental: ESN364 dose-2 group in Part 1<br>Healthy male subjects will receive a single dose of ESN364. | Drug: ESN364<br>* ESN364 will be administered orally.<br>|
| Placebo Comparator: Placebo group in Part 1<br>Healthy male subjects will receive a single dose of Placebo. | Drug: Placebo<br>* Placebo will be administered orally.<br>|
| Experimental: Male ESN364 group in Part 2<br>Healthy male subjects will receive a single dose of ESN364 followed by washout period, then receive once daily dosing of ESN364 for 10 consecutive days at the same dose level. | Drug: ESN364<br>* ESN364 will be administered orally.<br>|
| Experimental: Pre-menopausal female ESN364 group in Part 2<br>Healthy pre-menopausal female subjects will receive a single dose of ESN364 followed by washout period, then receive once daily dosing of ESN364 for 10 consecutive days at the same dose level. | Drug: ESN364<br>* ESN364 will be administered orally.<br>|
| Experimental: Post-menopausal female ESN364 group in Part 2<br>Healthy post-menopausal female subjects will receive a single dose of ESN364 followed by washout period, then receive once daily dosing of ESN364 for 10 consecutive days at the same dose level. | Drug: ESN364<br>* ESN364 will be administered orally.<br>|
| Placebo Comparator: Male placebo group in Part 2<br>Healthy male subjects will receive a single dose of Placebo followed by washout period, then receive once daily dosing of Placebo for 10 consecutive days. | Drug: Placebo<br>* Placebo will be administered orally.<br>|
| Placebo Comparator: Pre-menopausal female placebo group in Part 2<br>Healthy pre-menopausal female subjects will receive a single dose of Placebo followed by washout period, then receive once daily dosing of Placebo for 10 consecutive days. | Drug: Placebo<br>* Placebo will be administered orally.<br>|
| Placebo Comparator: Post-menopausal female placebo group in Part 2<br>Healthy post-menopausal female subjects will receive a single dose of Placebo followed by washout period, then receive once daily dosing of Placebo for 10 consecutive days. | Drug: Placebo<br>* Placebo will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by incidence of adverse events (AEs) in Part 1 | AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA). | Up to Day 12 in Part 1 | 
| Safety assessed by incidence of AEs in Part 2 | AEs will be coded using MedDRA. | 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. | 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. | 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. | 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. | 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. | 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. | Up to Day 24 in Part 2 | 
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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 | 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 | 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 | Up to an average of two weeks after last dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Before dosing on Day 2, 3, 5, 7 and 10 in MD part of Part 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP2693, Pharmacodynamics, Pharmacokinetics, ESN364, Safety