Study to Evaluate the Safety and Tolerability of ASP8062 in Healthy Japanese Male and Female Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and tolerability and evaluate pharmacokinetics of single and multiple ascending oral doses of ASP8062 in nonelderly Japanese male and female subjects.

Official Title
-----------------
ASP8062 Phase 1 Study - A Placebo-controlled, Single and Multiple Ascending Oral Dose Study in Non-elderly Healthy Japanese Male and Female Subjects -

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: ASP8062
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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: ≥ 17.6 kg/m^2 and < 26.4 kg/m^2 [BMI = Body weight (kg) ÷ {Body height (m)^2}]. Female subjects must agree to consistently use 2 forms of highly effective birth control starting at screening and throughout the study period and for 28 days after the final study drug administration. Female subjects must not donate ova starting at informed consent and throughout the clinical study period, and for 28 days after the final study drug administration. Male subjects and female spouse/partners who are of childbearing potential must be using condom and one of the highly effective birth control starting informed consent throughout the clinical study period and for 90 days after final study drug, if vasectomy is not performed for male subjects. Male subjects must not donate sperm starting at informed consent and throughout the clinical study period, and for 90 days after study drug administration. Exclusion Criteria: Subjects who participated or are scheduled to participate in any clinical trials or post-marketing studies within 120 days before screening test or during the screening test to the hospital admission (Day -2). Subjects who received or is scheduled to receive any medications (including over-the-counter drugs) within seven days before the 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 (Day -1). Subjects who meet any of the criterion for laboratory tests at screening or on the day of hospital admission (Day -2). Any deviation from the normal range of routine 12-lead ECG at screening. Subjects with a complication or history of drug allergies. Subjects who developed upper gastrointestinal symptoms (nausea, vomiting, stomachache, etc.) within seven days before the hospital admission. Subjects with a history of gastrointestinal resection except for appendicitis. Subjects with a complication or history of hepatic disease, cardiac disease, respiratory disease, gastrointestinal disease, renal disease, endocrine disease, cerebrovascular disease or malignant tumor. Subjects who received ASP8062 previously. Subject has a relevant history of suicide attempt or suicidal behavior.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 44 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP8062 lower dose<br>Subjects will receive a single dose of ASP8062 on Day 1, followed by 5 days of washout (Days 2-6) and once daily dosing for 14 consecutive days (Days 7-20) at the same dose level. | Drug: ASP8062<br>* ASP8062 will be administered orally.<br>|
| Experimental: ASP8062 middle dose<br>Subjects will receive a single dose of ASP8062 on Day 1, followed by 5 days of washout (Days 2-6) and once daily dosing for 14 consecutive days (Days 7-20) at the same dose level. | Drug: ASP8062<br>* ASP8062 will be administered orally.<br>|
| Experimental: ASP8062 higher dose<br>Subjects will receive a single dose of ASP8062 on Day 1, followed by 5 days of washout (Days 2-6) and once daily dosing for 14 consecutive days (Days 7-20) at the same dose level. | Drug: ASP8062<br>* ASP8062 will be administered orally.<br>|
| Placebo Comparator: Placebo<br>Subjects will receive a single dose of Placebo on Day 1, followed by 5 days of washout (Days 2-6) and once daily dosing for 14 consecutive days (Days 7-20) at the same dose level. | Drug: Placebo<br>* Placebo will be administered orally.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by incidence of adverse events | Adverse events (AEs) will be coded using Medical Dictionary for Regulatory Activities (MedDRA). | Up to Day 38 | 
| Safety assessed by vital signs: supine blood pressure | To assess the vital sign as a criteria of safety and tolerability variables. | Up to Day 38 | 
| Safety assessed by vital signs: supine pulse rate | To assess the vital sign as a criteria of safety and tolerability variables. | Up to Day 38 | 
| Safety assessed by vital signs: axillary body temperature | To assess the vital sign as a criteria of safety and tolerability variables. | Up to Day 38 | 
| Orthostatic challenge tests | To assess the orthostatic challenge tests as a criteria of safety and tolerability variables. | Up to Day 20 | 
| Safety assessed by laboratory tests: Hematology | To assess hematology as a criteria of safety and tolerability variables. | Up to Day 38 | 
| Safety assessed by laboratory tests: Biochemistry | To assess biochemistry as a criteria of safety and tolerability variables. | Up to Day 38 | 
| Safety assessed by laboratory tests: Urinalysis | To assess urinalysis as a criteria of safety and tolerability variables. | Up to Day 38 | 
| Safety assessed by 12-lead electrocardiogram | To assess the cardiovascular system functioning as a criteria of safety and tolerability variables. | Up to Day 21 | 
| Columbia-Suicide Severity Rating Scale | To assess the suicide risk | Up to Day 20 | 
| Safety assessed by body weight | To assess the body weight as a criteria of safety and tolerability variables. | Up to Day 38 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) parameter for ASP8062: Maximum observed concentration (Cmax) | To assess the PK of ASP8062 in single dose part and multiple dose part. | Up to Day 38 | 
| PK parameter for ASP8062: Time to maximum concentration (Tmax) | To assess the PK of ASP8062 in single dose part and multiple dose part. | Up to Day 38 | 
| PK parameter for ASP8062: Terminal elimination half-life (t1/2) | To assess the PK of ASP8062 in single dose part and multiple dose part. | Up to Day 38 | 
| PK parameter for ASP8062: Apparent total systemic clearance after single or multiple extra-vascular dosing (CL/F) | To assess the PK of ASP8062 in single dose part and multiple dose part. | Up to Day 38 | 
| PK parameter for ASP8062: Area under the concentration-time curve (AUC) from the time of dosing to 24 h after dosing (AUC24) | To assess the PK of ASP8062 in single dose part. | Up to Day 6 | 
| PK parameter for ASP8062: AUC from the time of dosing extrapolated to time infinity (AUCinf) | To assess the PK of ASP8062 in single dose part. | Up to Day 6 | 
| PK parameter for ASP8062: AUC from the time of dosing to the last measurable concentration (AUClast) | To assess the PK of ASP8062 in single dose part. | Up to Day 6 | 
| PK parameter for ASP8062: Time point prior to the time point corresponding to the first measurable (non-zero) concentration (tlag) | To assess the PK of ASP8062 in single dose part. | Up to Day 6 | 
| PK parameter for ASP8062: Apparent volume of distribution during the terminal elimination phase after single extra-vascular dosing (Vz/F) | To assess the PK of ASP8062 in single dose part. | Up to Day 6 | 
| PK parameter for ASP8062: AUC from the time of dosing to the start of the next dosing interval (AUCtau) | To assess the PK of ASP8062 in multiple dose part. | From Day 7 to Day 38 | 
| PK parameter for ASP8062: Concentration immediately prior to dosing at multiple dosing (Ctrough) | To assess the PK of ASP8062 in multiple dose part. | From Day 7 to Day 20 | 
| PK parameter for ASP8062: Percentage of AUCinf that is estimated by extrapolation (AUCinf (%extrap)) | To assess the PK of ASP8062 in single dose part | Up to Day 6 | 
| PK parameter for ASP8062: Terminal elimination rate constant (Lambda z) | To assess the PK of ASP8062 in single dose part and multiple dose part. | Up to Day 38 | 
| PK parameter for ASP8062: Time of the last measurable concentration (tlast) | To assess the PK of ASP8062 in single dose part and multiple dose part. | Up to Day 38 | 
| Accumulation Ratio (Rac) of Cmax | To assess the PK of ASP8062 in multiple dose part. | From Day 7 to Day 38 | 
| Rac of AUC | To assess the PK of ASP8062 in multiple dose part. | From Day 7 to Day 38 | 
| Peak-Trough Ratio for last dosing in multiple dose part | To assess the PK of ASP8062 in multiple dose part. | Day 20 and Day 21 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ASP8062, Pharmacokinetics, Safety