Bioequivalence Between Single Administration of ASC-01 (Aripiprazole/Sertraline Combination Drug) and Concomitant Single Administration of Aripiprazole and Sertraline, and Food Effect on Pharmacokinetics of ASC-01 in Healthy Male Adults

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03342963
• Collaborator: (none)
• Enrollment: 74
• Location: 1
• Arms: 4
• Actual Duration (Months): 1.9
• Patients Per Site Per Month: 38.8

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy Male Adults	Drug: ASC-01; Drug: Aripiprazole and sertraline	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-center, Open-label, Randomized, Two-treatment, Two-period Crossover Trial to Investigate Bioequivalence Between Single Administration of ASC-01 (Aripiprazole/Sertraline Combination Drug) and Concomitant Single Administration of Aripiprazole and Sertraline, and Food Effect on Pharmacokinetics of ASC-01 in Healthy Male Adults
• Actual Study Start Date: Nov 21, 2017
• Actual Primary Completion Date: Jan 18, 2018
• Actual Study Completion Date: Jan 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ASC-01 in period 1, Aripiprazole and sertraline in period 2 At Day 1 in Period I, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) will be administered after 10 or more hours of fasting. At Day 1 in Period II, Aripiprazole 3 mg and sertraline 100 mg will be administered after 10 or more hours of fasting.	Drug: ASC-01; Aripiprazole 3 mg/sertraline 100 mg combination drug; Drug: Aripiprazole and sertraline; Aripiprazole 3 mg and sertraline 100 mg
Experimental: Aripiprazole and sertraline in period 1, ASC-01 in period 2 At Day 1 in Period I, Aripiprazole 3 mg and sertraline 100 mg will be administered after 10 or more hours of fasting. At Day 1 in Period II, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) will be administered after 10 or more hours of fasting.	Drug: ASC-01; Aripiprazole 3 mg/sertraline 100 mg combination drug; Drug: Aripiprazole and sertraline; Aripiprazole 3 mg and sertraline 100 mg
Experimental: Fasting in period 1, After breakfast in period 2 At Day 1 in Period I, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) will be administered after 10 or more hours of fasting. At Day 1 in Period II, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) will be administered 30 minutes after the start of breakfast.	Drug: ASC-01; Aripiprazole 3 mg/sertraline 100 mg combination drug; Drug: Aripiprazole and sertraline; Aripiprazole 3 mg and sertraline 100 mg
Experimental: After breakfast in period 1, Fasting in period 2 At Day 1 in Period I, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) will be administered 30 minutes after the start of breakfast. At Day 1 in Period II, ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) will be administered after 10 or more hours of fasting.	Drug: ASC-01; Aripiprazole 3 mg/sertraline 100 mg combination drug; Drug: Aripiprazole and sertraline; Aripiprazole 3 mg and sertraline 100 mg

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 40 Years
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinic of Kyusyu Region	Fukuoka		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Oct 23, 2017
• Statistical Analysis Plan - Feb 19, 2018

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03342963
• Other Study ID Numbers: 031-102-00214; JapicCTI-173774
• First Posted: Nov 17, 2017
• Last Update Posted: May 3, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Aripiprazole; Sertraline

Study Results

Participant Flow

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.
Period Title: Overall Study
STARTED	27	27	10	10
COMPLETED	25	25	10	10
NOT COMPLETED	2	2	0	0

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	27	27	10	10	74
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	27 100%	27 100%	10 100%	10 100%	74 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	27 100%	27 100%	10 100%	10 100%	74 100%
Race/Ethnicity, Customized (Count of Participants)
Japanese	27 100%	27 100%	10 100%	10 100%	74 100%
Region of Enrollment (Count of Participants)
Japan	27 100%	27 100%	10 100%	10 100%	74 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set comprised subjects who received IMP and for whom plasma drug concentration data were obtained.

Arm/Group Title	ASC-01	Aripiprazole/Sertraline Concomitant
Arm/Group Description	ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.	Aripiprazole 3 mg and sertraline 100 mg was administered after 10 or more hours of fasting.
Measure Participants	40	39
Mean (Standard Deviation) [ng/mL]	18.8 (5.33)	16.9 (4.38)

2. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set comprised subjects who received IMP and for whom plasma drug concentration data were obtained.

Arm/Group Title	ASC-01	Aripiprazole/Sertraline Concomitant
Arm/Group Description	ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.	Aripiprazole 3 mg and sertraline 100 mg was administered after 10 or more hours of fasting.
Measure Participants	40	39
Mean (Standard Deviation) [ng*h/mL]	783 (273)	779 (236)

3. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set comprised subjects who received IMP and for whom plasma drug concentration data were obtained.

Arm/Group Title	ASC-01 Under Fasted	ASC-01 Under Fed
Arm/Group Description	ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.	ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered 30 minutes after the start of breakfast.
Measure Participants	20	20
Aripiprazole	16.9 (5.23)	16.6 (3.74)
Sertraline	28.9 (10.7)	36.5 (15.6)

4. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set comprised subjects who received IMP and for whom plasma drug concentration data were obtained.

Arm/Group Title	ASC-01 Under Fasted	ASC-01 Under Fed
Arm/Group Description	ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.	ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered 30 minutes after the start of breakfast.
Measure Participants	20	20
Aripiprazole	701 (221)	865 (219)
Sertraline	904 (415)	1060 (468)

Adverse Events

Time Frame	Treatment-emergent adverse events occurring up to 8 days after dosing date were collected.
Adverse Event Reporting Description	Safety Set comprised subjects who received IMP at least once.
Arm/Group Title	Cohort 1 - ASC-01		Cohort 1 - Aripiprazole/Sertraline Concomitant		Cohort 2 - ASC-01 Under Fasted		Cohort 2 - ASC-01 Under Fed
Arm/Group Description	ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.		Aripiprazole 3 mg and sertraline 100 mg was administered after 10 or more hours of fasting.		ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered after 10 or more hours of fasting.		ASC-01 (aripiprazole 3 mg/sertraline 100 mg combination drug) was administered 30 minutes after the start of breakfast.
All Cause Mortality
	Cohort 1 - ASC-01		Cohort 1 - Aripiprazole/Sertraline Concomitant		Cohort 2 - ASC-01 Under Fasted		Cohort 2 - ASC-01 Under Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/52 (0%)		0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Cohort 1 - ASC-01		Cohort 1 - Aripiprazole/Sertraline Concomitant		Cohort 2 - ASC-01 Under Fasted		Cohort 2 - ASC-01 Under Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/52 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 - ASC-01		Cohort 1 - Aripiprazole/Sertraline Concomitant		Cohort 2 - ASC-01 Under Fasted		Cohort 2 - ASC-01 Under Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/52 (84.6%)		43/52 (82.7%)		12/20 (60%)		14/20 (70%)
Cardiac disorders
Tachycardia	3/52 (5.8%)		2/52 (3.8%)		0/20 (0%)		0/20 (0%)
Gastrointestinal disorders
Diarrhoea	7/52 (13.5%)		9/52 (17.3%)		3/20 (15%)		1/20 (5%)
Nausea	39/52 (75%)		38/52 (73.1%)		11/20 (55%)		10/20 (50%)
Vomiting	20/52 (38.5%)		17/52 (32.7%)		6/20 (30%)		9/20 (45%)
Infections and infestations
Pharyngitis	0/52 (0%)		1/52 (1.9%)		0/20 (0%)		0/20 (0%)
Nasopharyngitis	0/52 (0%)		0/52 (0%)		0/20 (0%)		1/20 (5%)
Investigations
Blood creatine phosphokinase increased	1/52 (1.9%)		1/52 (1.9%)		0/20 (0%)		0/20 (0%)
Metabolism and nutrition disorders
Decreased appetite	4/52 (7.7%)		3/52 (5.8%)		1/20 (5%)		1/20 (5%)
Nervous system disorders
Dizziness postural	0/52 (0%)		1/52 (1.9%)		0/20 (0%)		2/20 (10%)
Headache	0/52 (0%)		1/52 (1.9%)		0/20 (0%)		0/20 (0%)
Vascular disorders
Orthostatic hypotension	0/52 (0%)		0/52 (0%)		0/20 (0%)		1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.