Healthy Adult Male
Conditions
Brief summary
The ratios of the geometric means of the ODT formulation to those of the reference formulation (conventional tablet) for the bioavailability variables (Cmax, AUCt, and AUC∞ of brexpiprazole (OPC-34712)).
Interventions
DRUGOPC-34712
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Capable of providing written informed consent prior to initiation of any trial-related procedures, and able, in the opinion of the investigator, to comply with all requirements of the trial
Exclusion criteria
* Clinically significant abnormality at the time of screening (eg, significant deviation from reference ranges) or in medical history that, in the opinion of investigator or sponsor may place the subject at risk or interfere with outcome variables, including drug absorption, distribution, metabolism, and excretion * History of serious mental disorder * History of drug or alcohol abuse within 2 years prior to screening * History of any significant drug allergy * Use of an investigational drug within 120 days prior to the first dosing of trial drug * Use of tobacco products or daily exposure to secondhand smoke within 2 months prior to screening * Consumption of grapefruit, grapefruit products, Seville oranges, Seville orange products, starfruit, or starfruit products within 72 hours prior to dosing * Use of prescription, over-the-counter, or herbal medication, vitamin supplements, or St. John's Wort within 14 days prior to the first dosing of trial drug, or of antibiotics within 30 days prior to the first dosing of trial drug * History of major surgery of the digestive tract (excluding appendectomy) * Any subject who, in the opinion of the investigator, should not participate in the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of OPC-34712 | Predose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96, 120，144, 168, 216, 264, and 312 hours postdose | To evaluate Cmax of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) of OPC-34712 | Predose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96, 120，144, 168, 216, 264, and 312 hours postdose | To evaluate AUC∞ of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation |
Countries
Japan
Participant flow
Pre-assignment details
A total of 33 subjects were screened for participation in this trial. Of the 33 subjects, 18 subjects were enrolled and randomized to one of 3 sequences, each consisting of 6 subjects. Of the 6 subjects in the Sequence 1 group, 6 subjects received a single dose of OPC-34712 orally disintegrating tablet (ODT) without water, 5 subjects received a single dose of OPC-34712 conventional tablet, and 4 subjects received a single dose of OPC-34712 ODT with water.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Subjects randomized to Sequence 1 received an ODT without water on Day 1, a conventional tablet on Day 21, and an ODT with water on Day 41. | 6 |
| Sequence 2 Subjects randomized to Sequence 2 received an ODT with water on Day 1, an ODT without water on Day 21, and a conventional tablet on Day 41. | 6 |
| Sequence 3 Subjects randomized to Sequence 3 received a conventional tablet on Day 1, an ODT with water on Day 21, and an ODT without water on Day 41. | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Positive urine test for cotinine on Day 20 or Day 40 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 5.5 | 29.7 years STANDARD_DEVIATION 7.4 | 28.7 years STANDARD_DEVIATION 8 | 30.4 years STANDARD_DEVIATION 6.9 |
| Race/Ethnicity, Customized Asian | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Region of Enrollment Japan | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 18 | 0 / 17 |
| other Total, other adverse events | 8 / 16 | 7 / 18 | 9 / 17 |
| serious Total, serious adverse events | 0 / 16 | 0 / 18 | 0 / 17 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) of OPC-34712
To evaluate AUC∞ of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation
Time frame: Predose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96, 120，144, 168, 216, 264, and 312 hours postdose
Population: Pharmacokinetic analysis set consisted of subjects with all evaluable PK parameters from enrolled subjects who had evaluable plasma concentrations. No data imputation was done for missing data, ie, missing data remained missing for the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-34712 Disintegrating Tablet With Water | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) of OPC-34712 | 2920 ng·h/mL | Standard Deviation 1630 |
| OPC-34712 Disintegrating Tablet Without Water | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) of OPC-34712 | 2830 ng·h/mL | Standard Deviation 1270 |
| OPC-34712 Conventional Tablet With Water | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) of OPC-34712 | 2770 ng·h/mL | Standard Deviation 1460 |
Primary
Maximum Plasma Concentration (Cmax) of OPC-34712
To evaluate Cmax of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation
Time frame: Predose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96, 120，144, 168, 216, 264, and 312 hours postdose
Population: Pharmacokinetic analysis set consisted of subjects with all evaluable PK parameters from enrolled subjects who had evaluable plasma concentrations. No data imputation was done for missing data, ie, missing data remained missing for the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-34712 Disintegrating Tablet With Water | Maximum Plasma Concentration (Cmax) of OPC-34712 | 47.4 ng/mL | Standard Deviation 10 |
| OPC-34712 Disintegrating Tablet Without Water | Maximum Plasma Concentration (Cmax) of OPC-34712 | 44.9 ng/mL | Standard Deviation 13.8 |
| OPC-34712 Conventional Tablet With Water | Maximum Plasma Concentration (Cmax) of OPC-34712 | 46.1 ng/mL | Standard Deviation 10.8 |