Trial Outcomes & Findings for Evaluation Study of the Bioavailability of Brexpiprazole Orally Disintegrating Tablets in Healthy Male Subjects (NCT NCT02875080)
NCT ID: NCT02875080
Last Updated: 2021-02-23
Results Overview
To evaluate Cmax of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
Predose, 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
2021-02-23
Participant Flow
A total of 33 subjects were screened for participation in this trial. Of the 33 subjects, 18 subjects were enrolled and randomized to one of 3 sequences, each consisting of 6 subjects. Of the 6 subjects in the Sequence 1 group, 6 subjects received a single dose of OPC-34712 orally disintegrating tablet (ODT) without water, 5 subjects received a single dose of OPC-34712 conventional tablet, and 4 subjects received a single dose of OPC-34712 ODT with water.
Participant milestones
| Measure |
Sequence 1
Subjects randomized to Sequence 1 received an ODT without water on Day 1, a conventional tablet on Day 21, and an ODT with water on Day 41.
|
Sequence 2
Subjects randomized to Sequence 2 received an ODT with water on Day 1, an ODT without water on Day 21, and a conventional tablet on Day 41.
|
Sequence 3
Subjects randomized to Sequence 3 received a conventional tablet on Day 1, an ODT with water on Day 21, and an ODT without water on Day 41.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
4
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
Subjects randomized to Sequence 1 received an ODT without water on Day 1, a conventional tablet on Day 21, and an ODT with water on Day 41.
|
Sequence 2
Subjects randomized to Sequence 2 received an ODT with water on Day 1, an ODT without water on Day 21, and a conventional tablet on Day 41.
|
Sequence 3
Subjects randomized to Sequence 3 received a conventional tablet on Day 1, an ODT with water on Day 21, and an ODT without water on Day 41.
|
|---|---|---|---|
|
Overall Study
Positive urine test for cotinine on Day 20 or Day 40
|
2
|
0
|
0
|
Baseline Characteristics
Evaluation Study of the Bioavailability of Brexpiprazole Orally Disintegrating Tablets in Healthy Male Subjects
Baseline characteristics by cohort
| Measure |
Sequence 1
n=6 Participants
Subjects randomized to Sequence 1 received an ODT without water on Day 1, a conventional tablet on Day 21, and an ODT with water on Day 41.
|
Sequence 2
n=6 Participants
Subjects randomized to Sequence 2 received an ODT with water on Day 1, an ODT without water on Day 21, and a conventional tablet on Day 41.
|
Sequence 3
n=6 Participants
Subjects randomized to Sequence 3 received a conventional tablet on Day 1, an ODT with water on Day 21, and an ODT without water on Day 41.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
32.8 years
STANDARD_DEVIATION 5.5 • n=5 Participants
|
29.7 years
STANDARD_DEVIATION 7.4 • n=7 Participants
|
28.7 years
STANDARD_DEVIATION 8.0 • n=5 Participants
|
30.4 years
STANDARD_DEVIATION 6.9 • 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
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Region of Enrollment
Japan
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Predose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96, 120，144, 168, 216, 264, and 312 hours postdosePopulation: Pharmacokinetic analysis set consisted of subjects with all evaluable PK parameters from enrolled subjects who had evaluable plasma concentrations. No data imputation was done for missing data, ie, missing data remained missing for the analyses.
To evaluate Cmax of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation
Outcome measures
| Measure |
OPC-34712 Disintegrating Tablet With Water
n=15 Participants
OPC-34712 (4 mg) orally disintegrating tablet is administered with water.
|
OPC-34712 Disintegrating Tablet Without Water
n=17 Participants
OPC-34712 (4 mg) orally disintegrating tablet is administered without water.
|
OPC-34712 Conventional Tablet With Water
n=17 Participants
OPC-34712 (4 mg) conventional tablet is administered with water.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of OPC-34712
|
47.4 ng/mL
Standard Deviation 10.0
|
44.9 ng/mL
Standard Deviation 13.8
|
46.1 ng/mL
Standard Deviation 10.8
|
PRIMARY outcome
Timeframe: Predose, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, 72, 96, 120，144, 168, 216, 264, and 312 hours postdosePopulation: Pharmacokinetic analysis set consisted of subjects with all evaluable PK parameters from enrolled subjects who had evaluable plasma concentrations. No data imputation was done for missing data, ie, missing data remained missing for the analyses.
To evaluate AUC∞ of OPC-34712 4-mg ODT formulation relative to 4-mg conventional tablet formulation
Outcome measures
| Measure |
OPC-34712 Disintegrating Tablet With Water
n=15 Participants
OPC-34712 (4 mg) orally disintegrating tablet is administered with water.
|
OPC-34712 Disintegrating Tablet Without Water
n=17 Participants
OPC-34712 (4 mg) orally disintegrating tablet is administered without water.
|
OPC-34712 Conventional Tablet With Water
n=17 Participants
OPC-34712 (4 mg) conventional tablet is administered with water.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) of OPC-34712
|
2920 ng·h/mL
Standard Deviation 1630
|
2830 ng·h/mL
Standard Deviation 1270
|
2770 ng·h/mL
Standard Deviation 1460
|
Adverse Events
OPC-34712 Disintegrating Tablet With Water
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
OPC-34712 Disintegrating Tablet Without Water
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
OPC-34712 Conventional Tablet With Water
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
OPC-34712 Disintegrating Tablet With Water
n=16 participants at risk
OPC-34712 (4 mg) orally disintegrating tablet is administered with water.
|
OPC-34712 Disintegrating Tablet Without Water
n=18 participants at risk
OPC-34712 (4 mg) orally disintegrating tablet is administered without water.
|
OPC-34712 Conventional Tablet With Water
n=17 participants at risk
OPC-34712 (4 mg) conventional tablet is administered with water.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
25.0%
4/16 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
27.8%
5/18 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
23.5%
4/17 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
1/16 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
5.6%
1/18 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
0.00%
0/17 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
6.2%
1/16 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
0.00%
0/18 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
0.00%
0/17 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
0.00%
0/18 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
0.00%
0/17 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
|
Nervous system disorders
Headache
|
0.00%
0/16 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
5.6%
1/18 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
0.00%
0/17 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
|
Vascular disorders
Orthostatic Hypotension
|
25.0%
4/16 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
16.7%
3/18 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
41.2%
7/17 • From the start of IMP administration throughout follow-up period (up to 22 days after the last dose of IMP)
A treatment-emergent adverse event (AE) was defined as an AE that started after start of IMP, or an AE that continued from baseline and became serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of trial medication. The safety analysis dataset included all subjects that were administered at least one dose of IMP.
|
Additional Information
Director of Clinical Trials
Otsuka Pharmaceutical Co., LTD.
Phone: +81-3-6361-7366
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place