The Pharmacokinetics, and Safety of Brexpiprazole Tablets in Chinese Healthy Subjects
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Multiple dose oral administration 1mg Once Daily (QD) , oral administration,14 consecutive days |
Drug: Brexpiprazole
Brexpiprazole , mutiple dose /oral/empty stomach
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Steady-state peak time (Tss_max) [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the steady-state peak time of Brexpiprazole
- Steady-state valley concentration(Css_min) [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the steady-state valley concentration of Brexpiprazole
- Steady-state peak concentration (Css_max) [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the steady-state peak concentration of Brexpiprazole
- Average steady-state plasma concentration (Css_av) [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the average steady-state plasma concentration (Css_av) of Brexpiprazole
- Half-life (t1/2, z) [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the Half-life of Brexpiprazole
- Steady-state clearance (CLss/F) [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the steady-state clearance of Brexpiprazole
- Area under steady state plasma concentration-time curve (AUC)ss [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the area under steady state plasma concentration-time curve of Brexpiprazole
- Fluctuation index (DF) [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the fluctuation index of Brexpiprazole
- Cumulative coefficient (RAUC, Rcmax) [Day1, Day2, Day10, Day11, Day12, Day13, Day14, Day15, Day16, Dv17, Day18, Day19, Dv21,Day23, Day25]
Assessment of the cumulative coefficient of Brexpiprazole
Secondary Outcome Measures
- The peak concentration (Cmax) after the first administration [Day1, Day2]
The peak concentration (Cmax) of Brexipiprazole and the metabolite DM-3411 on the first day after administration are calculated.
- The peak time (Tmax) after the first administration [Day1, Day2]
The peak-time of Brexipiprazole and the metabolite DM-3411 on the first day after administration are calculated.
- Area under the plasma concentration-time curve (AUC0-24h) [Day1, Day2]
The area under the plasma concentration-time curve of Brexipiprazole and the metabolite DM-3411 on the first day after administration are calculated.
- Valley concentration points [Day10, Day11, Day12, Day13, Day14]
Descriptive statistics about the valley concentration points before taking the study drug on days 10, 11, 12, 13 and 14
Eligibility Criteria
Criteria
Inclusion Criteria:
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- Sign the informed consent form
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- At the age of 18~45 years old (including upper and lower limits).
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- 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)].
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- No major disease or mental illness history. The test result is normal or without clinical significance , including serological examination (HIV antibodies, HBsAg, HCV antibodies and syphilis antibodies)), physical examination, vital signs (body temperature, blood pressure, pulse), 12 lead ECG, laboratory tests (routine blood tests, blood biochemical tests, routine urine tests, HbA1c test).
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- Agree to take adequate appropriate contraceptive measures during the trial and within 4 weeks after the last dose.
Exclusion Criteria:
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- Participated in any drug test within 12 weeks prior to enrollment.
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- Drug abuse in the past 2 years or a history of substance abuse.
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- 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.
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- Drug abuse urine test at screening is positive.
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- Taking grapefruit, seville orange, coffee, alcohol or food containing these ingredients one week before taking the study drug.
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- Taking any other prescriptions or over-the-counter medications or Chinese herbal medicine or vitamin 14 days prior to taking the study drug.
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- Use of any drug that inhibits or induces CYP2D6 and CYP3A4 metabolic enzymes 30 days prior to taking the study drug
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- At the discretion of the investigators, subjects' diet significantly deviates from normal intake of protein, carbohydrate and fat (e.g. vegetarians or absolute vegetarians).
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- Blood donation or equal blood loss (> 350 ml) within 12 weeks prior to medication.
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- Past or present allergy to any medication.
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- HbA1c ≥ 6.0% at screening.
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- Urinary pregnancy test (HCG) is positive at screening or female subjects who were in lactation.
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- Past or present lactose intolerance.
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- Breath alcohol test positive.
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- Any positive result in HIV antibody, HBsAg, HCV antibody and syphilis serology test.
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- Heart rate <50 bpm or >100 bpm at resting state.
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- Blood pressure at resting state in prone positon, sitting position or standing position > 140/90 mmHg, or < 90/60 mmHg.
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- Symptomatic hypotension or orthostatic hypotension (orthostatic hypotension is defined as standing blood pressure, systolic blood pressure (SBP) dropped ≥30 mmHg and/or diastolic blood pressure (DBP) decreased ≥20 mmHg after 3 minutes of resting pressure in the supine position or present symptoms).
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- Previous or current organic illness (including but not limited to cardiovascular, liver, kidney, nerve, digestive tract, respiratory tract, hematology, endocrine and immune diseases). Other conditions determined by the investigator could bring risk to the subjects or interfere the result of the trial, including but not limited to drug absorption, distribution, metabolism or excretion.
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- Previous or current psychological abnormality, mental or neurological disorders or autonomic neuropathies that are considered potential by investigators to compromise or influence the subject's ability to participate in the trial.
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- Subjects with abnormal digestion and absorption function (e.g. alimentary canal excision history ).
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- Other subjects determined by the investigators not fit for the enrollment of the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Anding Hospital of Capital Medical University | Beijing | Beijing | China | 100088 |
Sponsors and Collaborators
- Otsuka Beijing Research Institute
Investigators
- Principal Investigator: Tao Jiang, Master, Beijing Anding Hospital of Capital Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 331-403-00025