Trial Outcomes & Findings for Bioequivalence Study of Brexpiprazole Orally Disintegrating Tablets (ODT) 2mg (NCT NCT03902574)

NCT ID: NCT03902574

Last Updated: 2021-07-20

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

21 participants

Primary outcome timeframe

Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12,16, 24, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours postdose

Results posted on

2021-07-20

Participant Flow

Participant milestones

Participant milestones
Measure
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).
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).
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).
Overall Study
STARTED
7
7
7
Overall Study
COMPLETED
7
7
6
Overall Study
NOT COMPLETED
0
0
1

Reasons for withdrawal

Reasons for withdrawal
Measure
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).
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).
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).
Overall Study
Urinary drug test was positive on Day 20
0
0
1

Baseline Characteristics

Bioequivalence Study of Brexpiprazole Orally Disintegrating Tablets (ODT) 2mg

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Sequence 1: ODT Without Water/Conventional/ODT With Water
n=7 Participants
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).
Sequence 2: ODT With Water/ODT Without Water/Conventional
n=7 Participants
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).
Sequence 3: Conventional/ODT With Water/ODT Without Water
n=7 Participants
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).
Total
n=21 Participants
Total of all reporting groups
Age, Continuous
28.1 years
STANDARD_DEVIATION 6.6 • n=5 Participants
27.1 years
STANDARD_DEVIATION 5.4 • n=7 Participants
28.9 years
STANDARD_DEVIATION 5.4 • n=5 Participants
28.0 years
STANDARD_DEVIATION 5.6 • n=4 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
7 Participants
n=7 Participants
7 Participants
n=5 Participants
21 Participants
n=4 Participants
Race/Ethnicity, Customized
Asian
7 Participants
n=5 Participants
7 Participants
n=7 Participants
7 Participants
n=5 Participants
21 Participants
n=4 Participants
Region of Enrollment
Japan
7 Participants
n=5 Participants
7 Participants
n=7 Participants
7 Participants
n=5 Participants
21 Participants
n=4 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Conventional Tablet
n=19 Participants
Brexpiprazole conventional tablet 2 mg was administered with water.
ODT Without Water
n=19 Participants
Brexpiprazole ODT 2 mg was administered without water.
ODT With Water
n=19 Participants
Brexpiprazole ODT 2 mg was administered with water.
Maximum (Peak) Plasma Concentration (Cmax) of Brexpiprazole
23.31 ng/mL
Standard Deviation 4.722
24.24 ng/mL
Standard Deviation 6.090
23.75 ng/mL
Standard Deviation 5.320

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Conventional Tablet
n=19 Participants
Brexpiprazole conventional tablet 2 mg was administered with water.
ODT Without Water
n=19 Participants
Brexpiprazole ODT 2 mg was administered without water.
ODT With Water
n=19 Participants
Brexpiprazole ODT 2 mg was administered with water.
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
1340 ng*h/mL
Standard Deviation 629
1260 ng*h/mL
Standard Deviation 615

Adverse Events

Conventional Tablet

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

ODT Without Water

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

ODT With Water

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Conventional Tablet
n=21 participants at risk
Brexpiprazole conventional tablet 2 mg was administered with water.
ODT Without Water
n=20 participants at risk
Brexpiprazole ODT 2 mg was administered without water.
ODT With Water
n=20 participants at risk
Brexpiprazole ODT 2 mg was administered with water.
Gastrointestinal disorders
Nausea
4.8%
1/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
10.0%
2/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
Gastrointestinal disorders
Vomiting
4.8%
1/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
General disorders
Feeling Abnormal
4.8%
1/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
Hepatobiliary disorders
Hepatic Function Abnormal
4.8%
1/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
Infections and infestations
Gingivitis
0.00%
0/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
5.0%
1/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
Injury, poisoning and procedural complications
Contusion
4.8%
1/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
Investigations
Blood Urine Present
0.00%
0/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
5.0%
1/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
Nervous system disorders
Dizziness Postural
4.8%
1/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
5.0%
1/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
5.0%
1/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
Skin and subcutaneous tissue disorders
Rash
0.00%
0/21 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
0.00%
0/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).
5.0%
1/20 • Treatment-emergent adverse events were collected from the start of IMP administration up to 63 days
The safety analysis set consisted of all randomized subjects who received at least one dose of IMP. All the 21 subjects randomized to treatment sequences were included in the safety analysis set. (The number of subjects who received conventional tablet, ODT without water, and ODT with water were 21, 20, and 20, respectively).

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Results disclosure agreements

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