Schizophrenia
Conditions
Keywords
Schizophrenia,brexpiprazole,open-label,linical pharmacology
Brief summary
To evaluate the pharmacokinetics (PK), tolerability, and safety of brexpiprazole QW formulation administered as single and multiple doses in patients with schizophrenia.
Detailed description
A multi-center, open-label clinical pharmacology trial to investigate the PK, tolerability, and safety of brexpiprazole QW formulation administered as single and multiple doses. The trial comprises the single-dose period (Cohort 1) and the multiple-dose period (Cohort 2). The dose used in the multiple-dose period (Cohort 2) will be determined based on plasma drug concentrations obtained in the single-dose period (Cohort 1).
Interventions
DRUG2mg conventional tablet, once-weekly tablets
In each cohort, subjects will receive a brexpiprazole 2 mg conventional tablet on Day 1of Period 1, the QW formulation on Day 1 of Period 2 and 3, as single and multiple dose in a fasted state.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with a diagnosis of schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) 2. Patients capable of staying at the trial site from the day before investigational medicinal product (IMP) administration to the 8th day following IMP administration in both Period 1 and Period 2 3. Patients with a body mass index \[BMI = body weight (kg)/height (m)2\] of 18.5 or higher and lower than 35.0 at screening 4. Persons who provide written informed consent before commencement of any trial-related procedures and whom the investigator or subinvestigator judges to be capable of following all the conditions of this trial 5. Patients who, in the judgement of the investigator or subinvestigator, have stable psychotic symptoms maintained by administration of an antipsychotic (other than clozapine) within the dosing range indicated separately, before commencement of investigational medicinal product (IMP) administration
Exclusion criteria
1. Patients with a diagnosis of a concurrent mental disorder besides schizophrenia (schizoaffective disorder, major depressive disorder, bipolar I disorder, bipolar II disorder, general anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, dementia or mild neurocognitive disorder, personality disorder, etc) based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) (However, this exclusion does not apply to caffeine- or tobacco-related disorders) 2. Patients who fail to meet the specified requisite washout periods for the prohibited concomitant drugs and foods before commencement of IMP administration, or patients who are anticipated to take any of these drugs or foods during the study period 3. Patients who have previously undergone gastrointestinal surgery that could affect pharmacokinetic evaluations 4. Patients who are using clozapine at the time of informed consent 5. Patients who have received electro-convulsive therapy within 60 days before commencement of IMP administration 6. Patients with clinically problematic disorders of the nervous system, liver, kidneys, metabolic system, blood, immune system, cardiovascular system, lungs, or digestive system (However, such patients may be included if the condition is mild or well-controlled and is considered to not affect safety or pharmacokinetic evaluations.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1 | prepose, 2,4, 6, 8, 12, 24, 48, 72, 120, 168, 240, 312 hours postdose | To evaluate Cmax of OPC-34712 following single oral administration of the QW formulation (24 mg and 48 mg) and 2 mg conventional tablet . |
| Time to Maximum (Peak) Plasma Concentration (Tmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1 | prepose, 2,4, 6, 8, 12, 24, 48, 72, 120, 168, 240, 312 hours postdose | To evaluate Tmax of OPC-34712 following single oral administration of the QW formulation (24 mg and 48 mg) and 2 mg conventional tablet . |
| Cmax of OPC-34712 Following Multiple Oral Administrations of 48 mg QW Formulation in Cohort 2 Period 2 | prepose, 3, 9, 24, 36, 48, 72, 120, 168, 240, 312 hours postdose | To evaluate Tmax of OPC-34712 following multiple oral administration of the QW formulation 48 mg. |
| Tmax of OPC-34712 Following Multiple Oral Administrations of 48 mg QW Formulation in Cohort 2 Period 2 | prepose, 3, 9, 24, 36, 48, 72, 120, 168, 240, 312 hours postdose | To evaluate Tmax of OPC-34712 following multiple oral administration of the QW formulation 48 mg. |
Countries
Japan
Participant flow
Recruitment details
The total number of subjects who participated in Cohort 1 and Cohort 2 was 73.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Period 1 Subjects received a brexpiprazole 2 mg conventional tablet on Day 1. Subjects washed out brexpiprazole for 20 days until Cohort 1 Period 2. | 38 |
| Cohort 2 Period 1 Subjects received a brexpiprazole 2 mg conventional tablet on Day 1. Subjects washed out brexpiprazole for 20 days until Period 2(Cohort 2). | 35 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Trial terminated by sponsor | 0 | 12 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Cohort 2 Period 1 | Total | Cohort 1 Period 1 |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 10.6 | 46.9 years STANDARD_DEVIATION 10.1 | 46.8 years STANDARD_DEVIATION 9.7 |
| Race/Ethnicity, Customized Asian | 35 Participants | 73 Participants | 38 Participants |
| Region of Enrollment Japan | 35 Participants | 73 Participants | 38 Participants |
| Sex: Female, Male Female | 16 Participants | 30 Participants | 14 Participants |
| Sex: Female, Male Male | 19 Participants | 43 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 23 | 0 / 34 | 0 / 38 | 0 / 35 |
| other Total, other adverse events | 21 / 34 | 11 / 23 | 20 / 34 | 16 / 38 | 16 / 35 |
| serious Total, serious adverse events | 0 / 34 | 1 / 23 | 0 / 34 | 0 / 38 | 0 / 35 |
Outcome results
Primary
Cmax of OPC-34712 Following Multiple Oral Administrations of 48 mg QW Formulation in Cohort 2 Period 2
To evaluate Tmax of OPC-34712 following multiple oral administration of the QW formulation 48 mg.
Time frame: prepose, 3, 9, 24, 36, 48, 72, 120, 168, 240, 312 hours postdose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Tablet 2mg | Cmax of OPC-34712 Following Multiple Oral Administrations of 48 mg QW Formulation in Cohort 2 Period 2 | 225.0 ng/mL | Standard Deviation 147.7 |
Primary
Maximum Plasma Concentration (Cmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1
To evaluate Cmax of OPC-34712 following single oral administration of the QW formulation (24 mg and 48 mg) and 2 mg conventional tablet .
Time frame: prepose, 2,4, 6, 8, 12, 24, 48, 72, 120, 168, 240, 312 hours postdose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Tablet 2mg | Maximum Plasma Concentration (Cmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1 | 25.37 ng/mL | Standard Deviation 10.46 |
| QW Formuration 24mg | Maximum Plasma Concentration (Cmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1 | 98.62 ng/mL | Standard Deviation 46.76 |
| QW Formuration 48mg | Maximum Plasma Concentration (Cmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1 | 222.3 ng/mL | Standard Deviation 114.3 |
Primary
Time to Maximum (Peak) Plasma Concentration (Tmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1
To evaluate Tmax of OPC-34712 following single oral administration of the QW formulation (24 mg and 48 mg) and 2 mg conventional tablet .
Time frame: prepose, 2,4, 6, 8, 12, 24, 48, 72, 120, 168, 240, 312 hours postdose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Tablet 2mg | Time to Maximum (Peak) Plasma Concentration (Tmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1 | 4.00 hour |
| QW Formuration 24mg | Time to Maximum (Peak) Plasma Concentration (Tmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1 | 25.37 hour |
| QW Formuration 48mg | Time to Maximum (Peak) Plasma Concentration (Tmax) of OPC-34712 Following Single Oral Administration of 24 mg and 48 mg QW Formulation or 2 mg Conventional Tablet in Cohrt1 | 25.00 hour |
Primary
Tmax of OPC-34712 Following Multiple Oral Administrations of 48 mg QW Formulation in Cohort 2 Period 2
To evaluate Tmax of OPC-34712 following multiple oral administration of the QW formulation 48 mg.
Time frame: prepose, 3, 9, 24, 36, 48, 72, 120, 168, 240, 312 hours postdose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Tablet 2mg | Tmax of OPC-34712 Following Multiple Oral Administrations of 48 mg QW Formulation in Cohort 2 Period 2 | 24.61 hour |