The Pharmacokinetics, and Safety of Brexpiprazole Tablets in Chinese Healthy Subjects

Study Overview
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Brief Summary
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This study is a single-center, open-label study evaluating the pharmacokinetics and safety of multiple dose oral administration of Brexpiprazole (1 mg) tablets in Chinese healthy subject.10 healthy adult subjects will be enrolled in this study. A single dose (Brexpiprazole 1 mg) group is set and the test drug will be administered for 14 consecutive days.

Detailed Description
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10 healthy adult subjects will be enrolled in this study. A single dose (Brexpiprazole 1 mg) group is set and the test drug will be administered for 14 consecutive days. After receiving the informed consent form the subject themselves, the investigators start the screening 14 days to 1 days prior to taking the study drug (D-14 to D-1). One day before first dosing (D-1), subjects are hospitalized. On the next day (D1), after completed the hospitalization inspection, eligible subjects will be selected to start with the first dose, and from day 1 to day 14 (D1 to D14), continue once daily dosing and complete the corresponding inspection, observation and blood sampling. They continue hospitalization and are discharged on day 17 (D17) after completing the relevant examinations. On days 19, 21, 23，25 (D19, D21，D23 and D25), blood samples are collected and safety evaluation is performed. Telephone follow-up is performed on day 44 (D44, 30 days after the last dose of the drug). Subjects who early terminated the test after taking the study drug should be tested at the end of the study (D25/ET) as far as possible. Blood samples for pharmacokinetic evaluation are collected before daily dosing; D1 (before dosing, and 1, 2, 3, 4, 5, 6, 8, 12 hours after dosing), D2 (before dosing and 24 hours after first dosing), D10 (before dosing), D11 (before dosing), D12 (before dosing), D13 (before dosing), D14 (before dosing, and 1, 2, 3, 4, 5, 6, 8, 12 hours after dosing), D15 (24 hours after last dosing), D16 (48 hours after last dosing), D17 (72 hours after last dosing), D18 (96 hours after last dosing), D19 (120 hours after last dosing), D21 (168 hours after last dosing),D23 (216 hours after last dosing), D25 (264 hours after last dosing). 31 Blood samples collecting points in total.

Official Title
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A Single-center, Open-label Study Evaluating the Pharmacokinetics, and Safety of Multiple Dose Oral Brexpiprazole Tablets (1 mg) in Chinese Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Brexpiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Sign the informed consent form 2. At the age of 18 45 years old (including upper and lower limits). 3. Body weight of not less than 45 kg, body mass index 19   25kg/m2 range (including the upper and lower limits) [ body mass index (BMI) = body weight (kg) / height2 (m2)]. Exclusion Criteria: 1. Participated in any drug test within 12 weeks prior to enrollment. 2. Drug abuse in the past 2 years or a history of substance abuse. 3. Drinking alcohol more than 2 unit per day (1 unit= 360 ml beer , or 45 ml 4.0% alcohol, or 150 ml liquor, or 50 ml wine ) 6 months before the screening, or subjects can not stop drinking during the hospitalization. 4. Drug abuse urine test at screening is positive. Other protocol-defined inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiple dose oral administration<br>1mg Once Daily (QD) , oral administration,14 consecutive days | Drug: Brexpiprazole<br>* Brexpiprazole , mutiple dose /oral/empty stomach<br>* Other names: Brex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steady-state peak time (Tss_max) | Assessment of the steady-state peak time of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 
| Steady-state valley concentration(Css_min) | Assessment of the steady-state valley concentration of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 
| Steady-state peak concentration (Css_max) | Assessment of the steady-state peak concentration of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 
| Average steady-state plasma concentration (Css_av) | Assessment of the average steady-state plasma concentration (Css_av) of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 
| Half-life (t1/2, z) | Assessment of the Half-life of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 
| Steady-state clearance (CLss/F) | Assessment of the steady-state clearance of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 
| Area under steady state plasma concentration-time curve (AUC)ss | Assessment of the area under steady state plasma concentration-time curve of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 
| Fluctuation index (DF) | Assessment of the fluctuation index of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 
| Cumulative coefficient (RAUC, Rcmax) | Assessment of the cumulative coefficient of Brexpiprazole | Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The peak concentration (Cmax) after the first administration | The peak concentration (Cmax) of Brexipiprazole and the metabolite DM-3411 on the first day after administration are calculated. | Day1, Day2 | 
| The peak time (Tmax) after the first administration | The peak-time of Brexipiprazole and the metabolite DM-3411 on the first day after administration are calculated. | Day1, Day2 | 
| Area under the plasma concentration-time curve (AUC0-24h) | The area under the plasma concentration-time curve of Brexipiprazole and the metabolite DM-3411 on the first day after administration are calculated. | Day1, Day2 | 
| Valley concentration points | Descriptive statistics about the valley concentration points before taking the study drug on days 10, 11, 12, 13 and 14 | Day10, Day11, Day12, Day13, Day14 |