The Pharmacokinetics, Tolerability and Safety of Brexpiprazole in Healthy Chinese Subjects
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 mg dosing group Dosing group 1, single/oral/with fasting, Brexpiprazole 1.0 mg, 1 tablets |
Drug: Brexpiprazole
Brexpiprazole , single/oral/with fasting
Other Names:
|
| Experimental: 2 mg dosing group Dosing group 2, single/oral/with fasting, Brexpiprazole 1.0 mg, 2 tablets |
Drug: Brexpiprazole
Brexpiprazole , single/oral/with fasting
Other Names:
|
| Experimental: 4 mg dosing group Dosing group 3, single/oral/with fasting, Brexpiprazole 1.0 mg, 4 tablets |
Drug: Brexpiprazole
Brexpiprazole , single/oral/with fasting
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The peak concentration (Cmax) after the first administration [0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours]
The peak concentration (Cmax) of Brexipiprazole and the metabolite DM-3411 after administration
- The peak time (Tmax) after the first administration [0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours]
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 (AUC0-264h) [0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours]
The area under the plasma concentration-time curve of Brexipiprazole after administration are calculated.
- Half time after the first administration [0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours]
The half time of Brexipiprazole after administration are calculated.
- Apparent clearance after the first administration [0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours]
To assess the apparent clearance after administration (CL/F) of Brexipiprazole after the first administration
- 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]
To assess the Proportional dose-response relationship between pharmacokinetic parameters Cmax and AUC of OPC-34712
Secondary Outcome Measures
- Blood pressure [0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours]
To seeess blood pressure after administration of brexpiprazole
- Heart rate [0, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours]
To seeess heart rate after administration of brexpiprazole
- Body weight [1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264 hours]
To seeess Body weight after administration of brexpiprazole
- 12-lead ECG [3, 6, 24, 72, 96, 120, 264 hours]
To seeess 12-lead ECG after administration of brexpiprazole
- Blood biochemistry [24, 96, 264 hours]
To seeess blood biochemistry after administration of brexpiprazole
- Blood routine [24, 96, 264 hours]
To seeess blood routine after administration of brexpiprazole
- urinary routine [24, 96, 264 hours]
To seeess urinary routine after administration of brexpiprazole
Eligibility Criteria
Criteria
Inclusion Criteria:
-
- Sign the informed consent form
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2.At the age of 18~45 years old (including upper and lower limits) when signing the informed consent form.
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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)].
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4.Subjects determined by the investigator to be healthy according to the medical history and the results of serological examination (HIV antibodies, HBsAg, HCV antibodies and syphilis antibodies), physical examination, vital signs (body temperature, blood pressure, heart rate), 12 lead ECG, laboratory tests (routine blood tests, blood biochemical tests, routine urine tests).
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5.Subjects agree to take appropriate contraceptive measures during the trial and within 4 weeks after the dose.
Exclusion Criteria:
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- Participated in any interventional clinical trial within 12 weeks prior to enrollment.
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2.Drug abuse in the past 2 years or a history of abuse
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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
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4.Smoking urine test or drug abuse urine test at screening is positive.
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5.Taking grapefruit, seville orange, coffee, alcohol or food containing these ingredients one week before taking the study drug.
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6.Taking any other prescriptions or over-the-counter medications or Chinese herbal medicine or vitamin 14 days prior to taking the test medication
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7.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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8.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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9.Blood donation or equal blood loss (> 350 ml) within 12 weeks prior to medication.
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10.Past or present allergy to any medication.
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11.HbA1c ≥ 6.0% at screening.
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12.Urinary pregnancy test (HCG) is positive at screening or female subjects who were in lactation.
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13.Breath alcohol test positive.
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14.Any positive result in HIV antibody, HBsAg, HCV antibody and syphilis serology test.
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15.Heart rate <50 bpm or >100 bpm at resting state.
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16.Blood pressure at resting satate in prone positon, sitting position or standing position > 140/90 mmHg, or < 90/60 mmHg.
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17.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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18.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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19.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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20.Subjects with abnormal digestion and absorption function (e.g. alimentary canal excision history ).
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21.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.- 331-403-00024