ASP8302 Single and Multiple Ascending Oral Dose Study in Non-elderly Healthy Japanese Subjects

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety, tolerability and pharmacokinetic of single/multiple ascending oral doses of ASP8302 in non-elderly healthy Japanese male and female subjects.

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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: ASP8302
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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/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 120 days before screening test or during the screening test to the hospital admission (Day -2). Subjects who conducted or is scheduled to conduct any of the blood donation or blood drawing in designated period before Day -2 Subject who received or is scheduled to receive any medications within seven days before the hospital admission. Any deviation from any of the normal range of blood pressure, pulse rate, body temperature and standard 12-lead electrocardiogram at screening or on the day of hospital admission (Day -1). Subject who meets any of the criteria for laboratory tests at screening or on the day of hospital admission (Day -2). Any deviation from the normal range of routine 12-lead electrocardiogram at screening. Subjects with a complication or history of drug allergies. Subjects who developed upper gastrointestinal symptoms within seven days before the hospital admission. Subjects with a complication or history of hepatic disease. Subjects with a complication or history of cardiac disease. Subjects with a complication or history of respiratory disease except for history of asthma in childhood. Subjects with a complication or history of gastrointestinal disease except for a history of appendicitis. Subjects with a history of gastrointestinal resection except for appendicitis. Subjects with a complication or history of renal disease except for a history of calculus. Subjects with a complication or history of endocrine disease. Subjects with a complication or history of cerebrovascular disease. Subjects with a complication or history of malignant tumor. Subjects who received ASP8302 previously. Subjects who have a habit of excessive smoking or drinking alcohol.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 44 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: Single dose of ASP8302 dose-1<br>Subjects will receive a single dose of ASP8302. | Drug: ASP8302<br>* ASP8302 will be administered orally.<br>|
| Experimental: Single dose of ASP8302 dose-2<br>Subjects will receive a single dose of ASP8302. | Drug: ASP8302<br>* ASP8302 will be administered orally.<br>|
| Experimental: Single dose of ASP8302 dose-3<br>Subjects will receive a single dose of ASP8302. | Drug: ASP8302<br>* ASP8302 will be administered orally.<br>|
| Experimental: Single dose of ASP8302 dose-4<br>Subjects will receive a single dose of ASP8302. | Drug: ASP8302<br>* ASP8302 will be administered orally.<br>|
| Placebo Comparator: Single dose of Placebo<br>Subjects will receive a single dose of Placebo. | Drug: Placebo<br>* Placebo will be administered orally.<br>|
| Experimental: Multiple dose of ASP8302 dose-5<br>Subjects will receive once daily dosing of ASP8302 for 14 consecutive days at the same dose level. | Drug: ASP8302<br>* ASP8302 will be administered orally.<br>|
| Experimental: Multiple dose of ASP8302 dose-6<br>Subjects will receive once daily dosing of ASP8302 for 14 consecutive days at the same dose level. | Drug: ASP8302<br>* ASP8302 will be administered orally.<br>|
| Placebo Comparator: Multiple dose of Placebo<br>Subjects will receive once daily dosing of Placebo for 14 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) | Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA). | Up to Day 6 in single ascending dose (SAD) part Up to Day 19 in MAD part | 
| Safety assessed by vital signs: Body temperature | To assess vital signs as a criteria of safety variables. | Up to Day 6 in SAD part Up to Day 19 in multiple ascending dose (MAD) part | 
| Safety assessed by vital signs: Blood pressure | To assess vital signs as a criteria of safety variables. | Up to Day 6 in SAD part Up to Day 19 in MAD part | 
| Safety assessed by vital signs: Pulse rate | To assess vital signs as a criteria of safety variables. | Up to Day 6 in SAD part Up to Day 19 in MAD part | 
| Number of participants with laboratory value abnormalities and/or AEs | Number of participants with potentially clinically significant laboratory values. | Up to Day 6 in SAD part Up to Day 19 in MAD part | 
| Safety assessed by cardiac troponin | To assess the cardiovascular system function as a criteria of safety variables. | Up to Day 6 in SAD part Up to Day 19 in MAD part | 
| Safety assessed by standard 12-lead electrocardiogram | To assess the cardiovascular system function as a criteria of safety variables. | Up to Day 6 in SAD part Up to Day 19 in MAD part | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) parameter for ASP8302: Maximum observed concentration (Cmax) in plasma | To assess the PK of ASP8302 in SAD part and MAD part. | Up to 72 hr after dosing in SAD part Day 1 and Day 14 in MAD part | 
| PK parameter for ASP8302: Time of the Maximum Concentration (tmax) in plasma | To assess the PK of ASP8302 in SAD part and MAD part. | Up to 72 hr after dosing in SAD part Day 1 and Day 14 in MAD part | 
| PK parameter for ASP8302: Area under the concentration-time curve (AUC) from the time of dosing to 24h after dosing (AUC24) in plasma | To assess the PK of ASP8302 in SAD part and MAD part. | Up to 72 hr after dosing in SAD part Day 1 in MAD part | 
| PK parameter for ASP8302: AUC from the Time of Dosing Extrapolated to Time Infinity (AUCinf) in plasma | To assess the PK of ASP8302 in SAD part. | Up to 72 hr after dosing in SAD part | 
| PK parameter for ASP8302: AUC from the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) in plasma | To assess the PK of ASP8302 in MAD part. | Day 14 in MAD part | 
| PK parameter for ASP8302: Peak-Trough Ratio (PTR) in plasma | To assess the PK of ASP8302 in MAD part. | Day 14 in MAD part | 
| PK parameter for ASP8302: Accumulation Ratio for AUC (Rac(AUC)) in plasma | To assess the PK of ASP8302 in MAD part. | Day 14 in MAD part | 
| PK parameter for ASP8302: Accumulation Ratio for Cmax (Rac(Cmax)) in plasma | To assess the PK of ASP8302 in MAD part. | Day 14 in MAD part | 
| PK parameter for ASP8302: AUC from the Time of Dosing to the Last Measurable Concentration (AUClast) in plasma | To assess the PK of ASP8302 in SAD part. | Up to 72 hr after dosing in SAD part | 
| PK parameter for ASP8302: Time Point Prior to the Time Point Corresponding to the First Measurable (Non-zero) Concentration (tlag) in plasma | To assess the PK of ASP8302 in SAD part and MAD part. | Up to 72 hr after dosing in SAD part Day 1 in MAD part | 
| PK parameter for ASP8302: Terminal Elimination Half-life (t1/2) in plasma | To assess the PK of ASP8302 in SAD part and MAD part. | Up to 72 hr after dosing in SAD part Day 14 in MAD part | 
| PK parameter for ASP8302: Apparent Volume of Distribution during the Terminal Elimination Phase After Single Extra-Vascular Dosing (Vz/F) in plasma | To assess the PK of ASP8302 in SAD part. | Up to 72 hr after dosing in SAD part | 
| PK parameter for ASP8302: Apparent Total Systemic Clearance After Single or Multiple Extra-Vascular Dosing (CL/F) in plasma | To assess the PK of ASP8302 in SAD part and MAD part. | Up to 72 hr after dosing in SAD part Day 14 in MAD part | 
| PK parameter for ASP8302: Concentration Immediately Prior to Dosing at Multiple Dosing (Ctrough) in plasma | To assess the PK of ASP8302 in MAD part. | Up to Day 14 in MAD part | 
| PK parameter for ASP8302: Amount excreted into urine from the time of dosing to the 72 hours after dosing (Ae72) in urine | To assess the PK of ASP8302 in SAD part. | Up to 72 hr after dosing in SAD part | 
| PK parameter for ASP8302: Fraction excreted into urine from the time of dosing to the 72 hours after dosing (Ae72%) in urine | To assess the PK of ASP8302 in SAD part. | Up to 72 hr after dosing in SAD part | 
| PK parameter for ASP8302: Renal clearance (CLR) in urine | To assess the PK of ASP8302 in SAD part and MAD part. | Up to 72 hr after dosing in SAD part Day 14 in MAD part | 
| PK parameter for ASP8302: Amount excreted into urine over the time interval between consecutive dosing (Aetau) in urine | To assess the PK of ASP8302 in MAD part. | Day 14 in MAD part | 
| PK parameter for ASP8302: Fraction excreted into urine over the time interval between consecutive dosing (Aetau%) in urine | To assess the PK of ASP8302 in MAD part. | Day 14 in MAD part | 
| Pharmacodynamic (PD) parameter for ASP8302: Pupil diameter | To assess the PD of ASP8302 in SAD part and MAD part. | Up to 24 hr after dosing in SAD part Up to Day 14 in MAD part | 
| PD parameter for ASP8302: Salivary secretion | To assess the PD of ASP8302 in SAD part and MAD part. | Up to 24 hr after dosing in SAD part Up to Day 14 in MAD part | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Safety, ASP8302