Trial Outcomes & Findings for A Bioequivalence Study of ASC-01 Placebo (Aripiprazole 0 mg/Sertraline 100 mg) and Sertraline Tablet in Healthy Male Subjects (NCT NCT02088697)

NCT ID: NCT02088697

Last Updated: 2021-06-03

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 50 participants
• Primary outcome timeframe: predose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 144 and 168 hours postdose
• Results posted on: 2021-06-03

Participant Flow

Participant milestones

Measure	Arm A: ASC-01 Placebo First Period I: A single oral dose of ASC-01 placebo (aripiprazole 0 mg/sertraline 100 mg) was administered after 10 or more hours of fasting. Period II: A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting.	Arm B: Sertraline First Period I: A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting. Period II: A single oral dose of ASC-01 placebo (sertraline 100 mg) was administered after 10 or more hours of fasting.
Period I STARTED	25	25
Period I COMPLETED	24	21
Period I NOT COMPLETED	1	4
Wash-out Period (at Least 10 Days) STARTED	24	21
Wash-out Period (at Least 10 Days) COMPLETED	23	21
Wash-out Period (at Least 10 Days) NOT COMPLETED	1	0
Period II STARTED	23	21
Period II COMPLETED	23	21
Period II NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Arm A: ASC-01 Placebo First Period I: A single oral dose of ASC-01 placebo (aripiprazole 0 mg/sertraline 100 mg) was administered after 10 or more hours of fasting. Period II: A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting.	Arm B: Sertraline First Period I: A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting. Period II: A single oral dose of ASC-01 placebo (sertraline 100 mg) was administered after 10 or more hours of fasting.
Period I Physician Decision	1	4
Wash-out Period (at Least 10 Days) Adverse Event	1	0

Baseline Characteristics

A Bioequivalence Study of ASC-01 Placebo (Aripiprazole 0 mg/Sertraline 100 mg) and Sertraline Tablet in Healthy Male Subjects

Baseline characteristics by cohort

Measure	Arm A: ASC-01 Placebo First n=25 Participants Period I: A single oral dose of ASC-01 placebo (aripiprazole 0 mg/sertraline 100 mg) was administered after 10 or more hours of fasting. Period II: A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting.	Arm B: Sertraline First n=25 Participants Period I: A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting. Period II: A single oral dose of ASC-01 placebo (sertraline 100 mg) was administered after 10 or more hours of fasting.	Total n=50 Participants Total of all reporting groups
Age, Continuous	25.2 years STANDARD_DEVIATION 3.7 • n=5 Participants	28.5 years STANDARD_DEVIATION 4.3 • n=7 Participants	26.8 years STANDARD_DEVIATION 4.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Region of Enrollment Japan	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants

PRIMARY outcome

Timeframe: predose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 144 and 168 hours postdose

Population: Bioequivalence Analysis Set comprised all subjects for whom the Cmax and AUCt were determined in both Period I and Period II.

Outcome measures

Measure	ASC-01 Placebo n=44 Participants A single oral dose of ASC-01 placebo (aripiprazole 0 mg/sertraline 100 mg) was administered after 10 or more hours of fasting.	Sertraline n=44 Participants A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting.
Peak Plasma Concentration (Cmax) of Sertraline	28.3 ng/mL Standard Deviation 8.31	28.8 ng/mL Standard Deviation 10.1

SECONDARY outcome

Timeframe: predose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 144 and 168 hours postdose

Population: Bioequivalence Analysis Set comprised all subjects for whom the Cmax and AUCt were determined in both Period I and Period II.

Outcome measures

Measure	ASC-01 Placebo n=44 Participants A single oral dose of ASC-01 placebo (aripiprazole 0 mg/sertraline 100 mg) was administered after 10 or more hours of fasting.	Sertraline n=44 Participants A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting.
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Observable Concentration at Time t (AUCt) for Sertraline	835 ng*h/mL Standard Deviation 363	856 ng*h/mL Standard Deviation 421

Adverse Events

ASC-01 Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Sertraline

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	ASC-01 Placebo n=46 participants at risk A single oral dose of ASC-01 placebo (aripiprazole 0 mg/sertraline 100 mg) was administered after 10 or more hours of fasting.	Sertraline n=48 participants at risk A single oral dose of sertraline tablets (sertraline 100 mg) was administered after 10 or more hours of fasting.
Gastrointestinal disorders Nausea	10.9% 5/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	18.8% 9/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Gastrointestinal disorders Diarrhoea	6.5% 3/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	20.8% 10/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Gastrointestinal disorders Vomiting	0.00% 0/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	8.3% 4/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Investigations Blood bilirubin increased	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	2.1% 1/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Investigations Blood sodium decreased	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	4.2% 2/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Investigations Liver function test abnormal	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	0.00% 0/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Investigations White blood cell count increased	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	0.00% 0/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Investigations Blood creatine phosphokinase increased	0.00% 0/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	2.1% 1/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Investigations Eosinophil count increased	0.00% 0/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	2.1% 1/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Nervous system disorders Dizziness	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	0.00% 0/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Nervous system disorders Headache	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	2.1% 1/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Nervous system disorders Somnolence	0.00% 0/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	2.1% 1/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Nervous system disorders Tremor	0.00% 0/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	2.1% 1/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
General disorders Malaise	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	0.00% 0/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Infections and infestations Influenza	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	0.00% 0/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Renal and urinary disorders Ketonuria	2.2% 1/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	4.2% 2/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/46 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.	2.1% 1/48 • Treatment-emergent adverse events occurring up to 8 days after dosing date were collected. A single dose of ASC-01 placebo or sertraline tablet was administered to 25 subjects each in Period I, and a single dose of ASC-01 placebo or sertraline tablet was administered to 21 and 23 subjects, respectively, in Period II. In this trial, safety data for each formulation were summarized based on subjects treated with the respective formulation, and safety was therefore evaluated in 46 subjects receiving ASC-01 placebo and 48 subjects receiving sertraline tablets.

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: CL_OPCJ_RDA_Team@otsuka.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place