Healthy Adult Male
Conditions
Brief summary
To investigate the bioequivalence of brexpiprazole ODT 2 mg and brexpiprazole conventional tablet 2 mg
Interventions
DRUGBrexpiprazole ODT 2mg with water
Brexpiprazole ODT 2mg is administered with water.
DRUGBrexpiprazole ODT 2mg without water
Brexpiprazole ODT 2mg is administered without water.
DRUGBrexpiprazole conventional tablet 2mg
Brexpiprazole conventional tablet 2mg is administered with water.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Japanese males * BMI ［body weight in kg /(height in m)2］ of at least 18.5 kg/m2 and less than 25.0 kg/m2 (as a result of at the screening examination) * 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, subinvestigator, or sponsor may place the subject at risk or interfere with outcome variables such as 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 another investigational drug within 120 days prior to the first administration of IMP * Consumption of grapefruit, grapefruit products, Seville oranges, Seville orange products, Star fruit, or Star fruit products within 72 hours prior to the first administration of IMP or consumption of alcohol within 72 hours prior to administration of IMP * Use of prescription, over-the-counter (OTC), or herbal medication, or vitamin supplements, or consumption of food or beverages containing St. John's Wort within 14 days prior to the first administration of IMP, or use of antibiotics within 30 days prior to the first administration of IMP * History of major surgery of the digestive tract (excluding appendectomy) * Any subject who, in the judgement of the investigator or subinvestigator, should not participate in the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum (Peak) Plasma Concentration (Cmax) of Brexpiprazole | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12,16, 24, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours postdose |
| Area Under the Concentration-time Curve Calculated to the Last Observable Concentration at Time t (AUCt) of Brexpiprazole | Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12,16, 24, 48, 72, 96, 120, 144, 168, 216, 264, and 312 hours postdose |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: ODT Without Water/Conventional/ODT With Water Subjects randomized to Sequence 1 received a brexpiprazole ODT 2 mg without water on Day 1 in Period 1 (Days 1 to 20), then a brexpiprazole conventional tablet 2 mg on Day 21 in Period 2 (Days 21 to 40), then a brexpiprazole ODT 2 mg with water on Day 41 in Period 3 (Days 41 to 60). | 7 |
| Sequence 2: ODT With Water/ODT Without Water/Conventional Subjects randomized to Sequence 2 received a brexpiprazole ODT 2 mg with water on Day 1 in Period 1 (Days 1 to 20), then a brexpiprazole ODT 2 mg without water on Day 21 in Period 2 (Days 21 to 40), then a brexpiprazole conventional tablet 2 mg on Day 41 in Period 3 (Days 41 to 60). | 7 |
| Sequence 3: Conventional/ODT With Water/ODT Without Water Subjects randomized to Sequence 3 received a brexpiprazole conventional tablet 2 mg on Day 1 in Period 1 (Days 1 to 20), then a brexpiprazole ODT 2 mg with water on Day 21 in Period 2 (Days 21 to 40), then a brexpiprazole ODT 2 mg without water on Day 41 in Period 3 (Days 41 to 60). | 7 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Urinary drug test was positive on Day 20 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Sequence 1: ODT Without Water/Conventional/ODT With Water | Sequence 2: ODT With Water/ODT Without Water/Conventional | Sequence 3: Conventional/ODT With Water/ODT Without Water | Total |
|---|---|---|---|---|
| Age, Continuous | 28.1 years STANDARD_DEVIATION 6.6 | 27.1 years STANDARD_DEVIATION 5.4 | 28.9 years STANDARD_DEVIATION 5.4 | 28.0 years STANDARD_DEVIATION 5.6 |
| Race/Ethnicity, Customized Asian | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
| Region of Enrollment Japan | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 4 / 21 | 2 / 20 | 4 / 20 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Concentration-time Curve Calculated to the Last Observable Concentration at Time t (AUCt) of Brexpiprazole
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12,16, 24, 48, 72, 96, 120, 144, 168, 216, 264, and 312 hours postdose
Population: Bioequivalence analysis set: subjects for whom the relevant bioequivalence variables are available for all periods
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Tablet | Area Under the Concentration-time Curve Calculated to the Last Observable Concentration at Time t (AUCt) of Brexpiprazole | 1250 ng*h/mL | Standard Deviation 592 |
| ODT Without Water | Area Under the Concentration-time Curve Calculated to the Last Observable Concentration at Time t (AUCt) of Brexpiprazole | 1340 ng*h/mL | Standard Deviation 629 |
| ODT With Water | Area Under the Concentration-time Curve Calculated to the Last Observable Concentration at Time t (AUCt) of Brexpiprazole | 1260 ng*h/mL | Standard Deviation 615 |
Primary
Maximum (Peak) Plasma Concentration (Cmax) of Brexpiprazole
Time frame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12,16, 24, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours postdose
Population: Bioequivalence analysis set: subjects for whom the relevant bioequivalence variables are available for all periods
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Tablet | Maximum (Peak) Plasma Concentration (Cmax) of Brexpiprazole | 23.31 ng/mL | Standard Deviation 4.722 |
| ODT Without Water | Maximum (Peak) Plasma Concentration (Cmax) of Brexpiprazole | 24.24 ng/mL | Standard Deviation 6.09 |
| ODT With Water | Maximum (Peak) Plasma Concentration (Cmax) of Brexpiprazole | 23.75 ng/mL | Standard Deviation 5.32 |