The Pharmacokinetics, Tolerability and Safety of Brexpiprazole in Healthy Chinese 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, tolerability and safety of single dose oral brexpiprazole tablets in healthy Chinese subjects. A total of 30 healthy adult subjects are to be enrolled into the study. Three dose groups will be set up, with about 10 subjects in each dose group. Subjects will enter 1 mg, 2 mg and 4 mg dose groups in sequence.

Detailed Description
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A total of 30 healthy adult subjects are to be enrolled into the study. Three dose groups will be set up, with about 10 subjects in each dose group. Subjects will enter 1 mg, 2 mg and 4 mg dose groups in sequence. After the clinical trial responsible physicians obtain the informed consent forms from subjects, the subjects will be screened 14 days to 1 days prior to taking the study drug (D-14 D-1). One day prior to dosing in each group (D-1), the included subjects are hospitalized On the next day (D1), after completed the hospitalization inspection, eligible subjects will be assigned subject numbers to start with the first dose, complete corresponding examination, stay in hospital for observation and be discharged on Day 4 of medication. On days 6, 8, 10, 12 blood samples are collected and safety evaluation will be performed. Telephone follow-up will be performed on day Day31. Blood samples are collected to determine and evaluate blood concentrations of Brexpiprazole and its main metabolite DM-3411 before dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours after dosing, with 18 sampling points in total.

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

Conditions
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Health

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) when signing the informed consent form. 3.Body weight of not less than 50kg, BMI 19   24kg/m2 (including the upper and lower limits) [ body mass index (BMI) = body weight (kg) / height2 (m2)]. Exclusion Criteria: 1. Participated in any interventional clinical trial within 12 weeks prior to enrollment. 2.Drug abuse in the past 2 years or a history of 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

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 mg dosing group<br>Dosing group 1, single/oral/with fasting, Brexpiprazole 1.0 mg, 1 tablets | Drug: Brexpiprazole<br>* Brexpiprazole , single/oral/with fasting<br>* Other names: Brex;|
| Experimental: 2 mg dosing group<br>Dosing group 2, single/oral/with fasting, Brexpiprazole 1.0 mg, 2 tablets | Drug: Brexpiprazole<br>* Brexpiprazole , single/oral/with fasting<br>* Other names: Brex;|
| Experimental: 4 mg dosing group<br>Dosing group 3, single/oral/with fasting, Brexpiprazole 1.0 mg, 4 tablets | Drug: Brexpiprazole<br>* Brexpiprazole , single/oral/with fasting<br>* Other names: Brex;|

What is the study measuring?
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Primary 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 after administration | 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 
| 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. | 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 
| Area under the plasma concentration-time curve (AUC0-264h) | The area under the plasma concentration-time curve of Brexipiprazole after administration are calculated. | 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 
| Half time after the first administration | The half time of Brexipiprazole after administration are calculated. | 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 
| Apparent clearance after the first administration | To assess the apparent clearance after administration (CL/F) of Brexipiprazole after the first administration | 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 
| Proportional dose-response relationship between pharmacokinetic parameters Cmax and AUC of OPC-34712 | To assess the Proportional dose-response relationship between pharmacokinetic parameters Cmax and AUC of OPC-34712 | 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | To seeess blood pressure after administration of brexpiprazole | 0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 
| Heart rate | To seeess heart rate after administration of brexpiprazole | 0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 
| Body weight | To seeess Body weight after administration of brexpiprazole | 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours | 
| 12-lead ECG | To seeess 12-lead ECG after administration of brexpiprazole | 3, 6, 24, 72, 96, 120, 264 hours | 
| Blood biochemistry | To seeess blood biochemistry after administration of brexpiprazole | 24, 96, 264 hours | 
| Blood routine | To seeess blood routine after administration of brexpiprazole | 24, 96, 264 hours | 
| urinary routine | To seeess urinary routine after administration of brexpiprazole | 24, 96, 264 hours |