Healthy Male Adults
Conditions
Brief summary
To investigate the bioequivalence of aripiprazole between administration of one ASC-01 tablet (aripiprazole 3 mg/sertraline 100 mg combination drug) and concomitant administration of one aripiprazole 3-mg tablet and two sertraline 50-mg tablets (Cohort 1). To investigate food effect on plasma pharmacokinetics of aripiprazole and sertraline by single oral administration of ASC-01 under a fasting or fed condition (Cohort 2).
Interventions
DRUGASC-01
Aripiprazole 3 mg/sertraline 100 mg combination drug
DRUGAripiprazole and sertraline
Aripiprazole 3 mg and sertraline 100 mg
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subject at the age between 20 and 40 at the time of informed consent * Subject has a body mass index (BMI = body weight \[kg\]/height \[m\]2) of ≥18.5 and \<25.0 kg/m2 at screening * Subject is providing consent for participation in this trial in writing prior to the start of the procedures related to this trial, and judged by the investigator or subinvestigator to be capable of observing procedures in this trial.
Exclusion criteria
* Subject has a clinically significant abnormality in physical findings at screening or in medical history that in the investigator's or subinvestigator's opinion may place the subject at risk or interfere with outcome variables including drug absorption, distribution, metabolism, and excretion. * Subject is judged by the investigator or subinvestigator to be inappropriate for participation in this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peak Plasma Concentration (Cmax) of Aripiprazole in Cohort 1 | Baseline, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72,96, 144 and 168h after dosing |
| Area Under the Plasma Concentration Versus Time Curve 168h (AUC168h) of Aripiprazole in Cohort 1 | Baseline, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72,96, 144 and 168h after dosing |
| Cmax of Aripiprazole and Sertraline in Cohort 2 | Baseline, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72,96, 144 and 168h after dosing |
| AUC168h of Aripiprazole and Sertraline in Cohort 2 | Baseline, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72,96, 144 and 168h after dosing |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: ASC-01 First At Day 1 in Period I, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.
At Day 1 in Period II, Aripiprazole 3 mg and sertraline 100 mg was administered after 10 or more hours of fasting.
There was a washout period of at least 35 days between Period I and Period II. | 27 |
| Cohort 1: Aripiprazole/Sertraline Concomitant First At Day 1 in Period I, Aripiprazole 3 mg and sertraline 100 mg was administered after 10 or more hours of fasting.
At Day 1 in Period II, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.
There was a washout period of at least 35 days between Period I and Period II. | 27 |
| Cohort 2: ASC-01 Under Fasted First At Day 1 in Period I, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.
At Day 1 in Period II, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered 30 minutes after the start of breakfast.
There was a washout period of at least 35 days between Period I and Period II. | 10 |
| Cohort 2: ASC-01 Under Fed First At Day 1 in Period I, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered 30 minutes after the start of breakfast.
At Day 1 in Period II, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.
There was a washout period of at least 35 days between Period I and Period II. | 10 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: ASC-01 First | Cohort 1: Aripiprazole/Sertraline Concomitant First | Cohort 2: ASC-01 Under Fasted First | Cohort 2: ASC-01 Under Fed First | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 27 Participants | 10 Participants | 10 Participants | 74 Participants |
| Race/Ethnicity, Customized Japanese | 27 Participants | 27 Participants | 10 Participants | 10 Participants | 74 Participants |
| Region of Enrollment Japan | 27 Participants | 27 Participants | 10 Participants | 10 Participants | 74 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 27 Participants | 27 Participants | 10 Participants | 10 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 52 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 44 / 52 | 43 / 52 | 12 / 20 | 14 / 20 |
| serious Total, serious adverse events | 0 / 52 | 0 / 52 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve 168h (AUC168h) of Aripiprazole in Cohort 1
Time frame: Baseline, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72,96, 144 and 168h after dosing
Population: Pharmacokinetic Analysis Set comprised subjects who received IMP and for whom plasma drug concentration data were obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASC-01 | Area Under the Plasma Concentration Versus Time Curve 168h (AUC168h) of Aripiprazole in Cohort 1 | 783 ng*h/mL | Standard Deviation 273 |
| Aripiprazole/Sertraline Concomitant | Area Under the Plasma Concentration Versus Time Curve 168h (AUC168h) of Aripiprazole in Cohort 1 | 779 ng*h/mL | Standard Deviation 236 |
Primary
AUC168h of Aripiprazole and Sertraline in Cohort 2
Time frame: Baseline, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72,96, 144 and 168h after dosing
Population: Pharmacokinetic Analysis Set comprised subjects who received IMP and for whom plasma drug concentration data were obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ASC-01 | AUC168h of Aripiprazole and Sertraline in Cohort 2 | Sertraline | 904 ng*h/mL | Standard Deviation 415 |
| ASC-01 | AUC168h of Aripiprazole and Sertraline in Cohort 2 | Aripiprazole | 701 ng*h/mL | Standard Deviation 221 |
| Aripiprazole/Sertraline Concomitant | AUC168h of Aripiprazole and Sertraline in Cohort 2 | Sertraline | 1060 ng*h/mL | Standard Deviation 468 |
| Aripiprazole/Sertraline Concomitant | AUC168h of Aripiprazole and Sertraline in Cohort 2 | Aripiprazole | 865 ng*h/mL | Standard Deviation 219 |
Primary
Cmax of Aripiprazole and Sertraline in Cohort 2
Time frame: Baseline, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72,96, 144 and 168h after dosing
Population: Pharmacokinetic Analysis Set comprised subjects who received IMP and for whom plasma drug concentration data were obtained.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ASC-01 | Cmax of Aripiprazole and Sertraline in Cohort 2 | Aripiprazole | 16.9 ng/mL | Standard Deviation 5.23 |
| ASC-01 | Cmax of Aripiprazole and Sertraline in Cohort 2 | Sertraline | 28.9 ng/mL | Standard Deviation 10.7 |
| Aripiprazole/Sertraline Concomitant | Cmax of Aripiprazole and Sertraline in Cohort 2 | Aripiprazole | 16.6 ng/mL | Standard Deviation 3.74 |
| Aripiprazole/Sertraline Concomitant | Cmax of Aripiprazole and Sertraline in Cohort 2 | Sertraline | 36.5 ng/mL | Standard Deviation 15.6 |
Primary
Peak Plasma Concentration (Cmax) of Aripiprazole in Cohort 1
Time frame: Baseline, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72,96, 144 and 168h after dosing
Population: Pharmacokinetic Analysis Set comprised subjects who received IMP and for whom plasma drug concentration data were obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASC-01 | Peak Plasma Concentration (Cmax) of Aripiprazole in Cohort 1 | 18.8 ng/mL | Standard Deviation 5.33 |
| Aripiprazole/Sertraline Concomitant | Peak Plasma Concentration (Cmax) of Aripiprazole in Cohort 1 | 16.9 ng/mL | Standard Deviation 4.38 |