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Trial record 15 of 64 for:    brexpiprazole

PET Trial to Assess the Receptor Occupancy of Brexpiprazole in Adult Subjects With Schizophrenia

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ClinicalTrials.gov Identifier: NCT01854944
Recruitment Status : Completed
First Posted : May 16, 2013
Results First Posted : February 4, 2016
Last Update Posted : February 4, 2016
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Schizophrenia
Intervention Drug: Brexpiprazole 1mg to 4mg
Enrollment 12
Recruitment Details A Phase 1, single center, open-label trial of up to 12 enrolled participants.
Pre-assignment Details Participants were at the inpatient unit in the New York State Psychiatric Institute between Days -22 and -2. Participants remained inpatient during the drug-free interval at the principal investigator's discretion.
Arm/Group Title Cohort 1 - Brexpiprazole 4 mg Cohort 2 - Brexpiprazole 1 mg Cohort 3 - Brexpiprazole 4 mg
Hide Arm/Group Description Participants in cohort 1 received 1 milligram (mg) tablet of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10. Participants in cohort 2 received 1-mg tablet of brexpiprazole once daily on Days 1 to 10. Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Period Title: Overall Study
Started 4 4 4
Completed 4 4 3
Not Completed 0 0 1
Reason Not Completed
Withdrawal by Subject             0             0             1
Arm/Group Title Cohort 1 - Brexpiprazole 4 mg Cohort 2 - Brexpiprazole 1 mg Cohort 3 - Brexpiprazole 4 mg Total
Hide Arm/Group Description Participants in cohort 1 received 1-mg tablet of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10. Participants in cohort 2 received 1-mg tablet of brexpiprazole once daily on Days 1 to 10. Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10. Total of all reporting groups
Overall Number of Baseline Participants 4 4 4 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 4 participants 4 participants 12 participants
38.3  (4.4) 40.8  (11.9) 45  (6.9) 41.3  (8.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 12 participants
Female
3
  75.0%
1
  25.0%
1
  25.0%
5
  41.7%
Male
1
  25.0%
3
  75.0%
3
  75.0%
7
  58.3%
1.Primary Outcome
Title Change in Percentage Dopamine D2/D3 Receptor Occupancy
Hide Description Dopamine receptor occupancy measured using the radiotracer [11C]-(+)-PHNO in low and high dose. The binding of brexpiprazole to the D2/D3 receptors were assessed by comparing the binding potential from the Baseline scan (prior to treatment) to that of Day 10 (after treatment). The D2/D3 receptors following administration of a 1- and 4-mg doses of brexpiprazole were assessed and the occupancy estimates were averaged across brain regions 4 hours post-last dose on Day 10.
Time Frame Baseline to 4 hours post-last dose on Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The positron emission tomography (PET) analysis included all participants who had both the Baseline and Day 10 PET scans performed.
Arm/Group Title Brexpiprazole 1mg Brexpiprazole 4 mg
Hide Arm/Group Description:
Participants received 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants received 1-mg brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4
Mean (Standard Deviation)
Unit of Measure: percentage occupancy
6-region model (D2 receptor) 36  (16) 59  (5)
6-region model (D3 receptor) 2  (3) 13  (10)
8-region model (D2 receptor) 27  (25) 67  (15)
8-region model (D3 receptor) 1  (2) 31  (8)
2.Primary Outcome
Title Change in Percentage 5-HT1A Receptor Occupancy
Hide Description Mean (±SD) Serotonin 5-HT1A Receptor Occupancy Using the Radiotracer [11C]CUMI101 in high dose only. In cohorts 1, 2 and 3, the binding of brexpiprazole to the 5-HT1A receptors was assessed by comparing the binding potential from the Baseline scan (prior to treatment) to that of Day 10 (after treatment). The 5-HT1A receptors following administration of a 4-mg dose of brexpiprazole was assessed and the occupancy estimates were averaged across brain regions 4 hours post-last dose on Day 10.
Time Frame Baseline to 4 hours post-last dose on Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The PET analysis included all participants who had both the Baseline and Day 10 PET scans performed.
Arm/Group Title Brexpiprazole 4mg
Hide Arm/Group Description:
Participants received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: percentage occupancy
4  (6)
3.Primary Outcome
Title Change in Percentage 5-HT2A Receptor Occupancy
Hide Description Mean (±SD) Serotonin 5-HT2A Receptor Occupancy Using the Radiotracer [11C]MDL100907 (in low and high dose). The 5-HT2A receptors following administration of 1- and 4-mg doses of brexpiprazole were assessed and the occupancy estimates were averaged across brain regions 4 hours post-last dose on Day 10.
Time Frame Baseline and 4 hours post-last dose on Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The PET analysis included all participants who had both the Baseline and Day 10 PET scans performed.
Arm/Group Title Brexpiprazole 1mg Brexpiprazole 4 mg
Hide Arm/Group Description:
Participants received 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants received 1-mg brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4
Mean (Standard Deviation)
Unit of Measure: percentage occupancy
28  (10) 45  (7)
4.Primary Outcome
Title Change in Occupancy at Serotonin Transporter (SERT)
Hide Description Mean (±SD) SERT Occupancy Using the Radiotracer [11C]DASB in high dose only. Occupancy estimates were averaged across brain regions 4 hours post-last dose.
Time Frame Baseline to 4 hours post-last dose on Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The PET analysis included all participants who had both the Baseline and Day 10 PET scans performed.
Arm/Group Title Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: percentage occupancy
-3  (15)
5.Secondary Outcome
Title Area Under the Concentration-time Curve (AUCτ) During a Dosing Interval at Steady-state for Brexpiprazole and Its Metabolite DM-3411
Hide Description AUC during a dosing interval at steady-state for brexpiprazole and its metabolite DM-3411. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.
Time Frame Baseline to Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis included participants who had valid measurements (per clinical pharmacology). Blood samples were collected on Days 1 and 9 at predose and Day 10 at predose and at 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-last dose or at early termination (ET).
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2 - Brexpiprazole 1mg Cohort 3 - Brexpiprazole 4 mg
Hide Arm/Group Description:
Participants in Cohort 1 received 1-mg tablet of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in Cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in Cohort 3 received one 1- to 4-mg dose of brexpiprazole (at the investigator’s discretion) once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
Brexpiprazole 2520  (1290) 716  (118) 1410  (352)
DM-3411 807  (205) 329  (227) 761  (397)
6.Secondary Outcome
Title Peak (Maximal) Concentration of Drug in Plasma (Cmax) for Brexpiprazole and Its Metabolite DM-3411
Hide Description (Cmax) Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.
Time Frame Baseline to Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis included participants who had valid measurements (per clinical pharmacology). Blood samples were collected on Days 1 and 9 at predose and Day 10 at predose and at 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-last dose or at ET.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2- Brexpiprazole 1mg Cohort 3 - Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
Brexpiprazole 126  (58.3) 46.5  (7.47) 70.9  (18.8)
DM-3411 37.1  (10.8) 17.3  (10.4) 35.7  (18.6)
7.Secondary Outcome
Title Apparent Clearance of Drug From Plasma After Extravascular Administration (CL/F; Only Brexpiprazole)
Hide Description PK parameter - CL/F was assessed for brexpiprazole only. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.
Time Frame Baseline to Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis included participants who had valid measurements (per clinical pharmacology). Blood samples were collected on Days 1 and 9 at predose and Day 10 at predose and at 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-last dose or at ET.
Arm/Group Title Cohort 1 - Brexpiprazole 4 mg Cohort 2 - Brexpiprazole 1mg Cohort 3 - Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: mL/hr
1960  (960) 1420  (242) 2970  (831)
8.Secondary Outcome
Title Time to Maximum (Peak) Plasma Concentration (Tmax) for Brexpiprazole and Its Metabolite DM-3411
Hide Description Tmax for brexpiprazole and its metabolite DM-3411. Days 1 and 9: predose (within 15 minutes prior to dosing) Day 10: predose (within 15 minutes prior to dosing) and 1, 2, 3, 4, 5, 6, 8, and 12 hours post-last dose.
Time Frame Baseline to Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis included participants who had valid measurements (per clinical pharmacology). Blood samples were collected on Days 1 and 9 at predose and Day 10 at predose and at 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-last dose or at ET.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2 - Brexpiprazole 1mg Cohort 3 - Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received once 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Median (Full Range)
Unit of Measure: hour
Brexpiprazole
1.92
(0.00 to 2.92)
1.50
(0.93 to 1.93)
4.87
(3.10 to 6.00)
DM-3411
2.42
(0.00 to 24.08)
1.51
(0.00 to 11.92)
11.87
(3.10 to 24.00)
9.Secondary Outcome
Title Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score
Hide Description The AIMS Scale was an extrapyramidal symptoms (EPS) rating scale. The AIMS is a 12 item scale. The first 10 items e.g. facial and oral movements (items 1-4), extremity movements (items 5 and 6), trunk movements (item 7), investigators global assessment of dyskinesia (items 8 to 10). The first 10 items are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28, with a higher score indicating worse outcome. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.
Time Frame Baseline to Day 6, 11 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2 - Brexpiprazole 1mg Cohort 3 Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Day 6 0  (0) 0  (0) 0.3  (0.5)
Day 11 0  (0) 0  (0) 0  (0)
Last Visit 0  (0) 0  (0) 0  (0)
10.Secondary Outcome
Title Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score
Hide Description The SAS is a rating scale used to measure EPS. The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40, with higher scores indicating worse outcome. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.
Time Frame Baseline to Day 6, 11 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2- Brexpiprazole 1mg Cohort 3 Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received once 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Units on scale
Day 6 0.3  (0.5) 0  (0) -0.3  (1.3)
Day 11 0  (0) 0  (0) -0.7  (1.2)
Last Visit 0  (0) 0  (0) -0.5  (1.0)
11.Secondary Outcome
Title Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score
Hide Description The BARS consisted of 4 items related to akathisia: objective observation of akathisia by the study physician, subjective feelings of restlessness by the participant, participant distress due to akathisia, and global evaluation of akathisia. The first 3 items were rated on a 4-point scale, with a score of 0 = absence of symptoms and a score of 3 = severe condition. The global clinical evaluation were made on a 6-point scale, (0=absent, 1=questionable, 2=mild, 3=moderate, 4=marked, 5=severe). To complete this scale, participants were observed while they were seated and then stood for a minimum of 2 minutes in each position. Symptoms observed in other situations (e.g., while engaged in neutral conversation or engaged in activity on the ward) may also be rated. Subjective phenomena were to be elicited by direct questioning. The BARS total score (when combined) ranged from 0 to 18, with higher values indicating a severe condition.
Time Frame Baseline to Day 6, 11 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2- Brexpiprazole 1mg Cohort 3 Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Day 6 0.5  (1.0) 0  (0) 0.5  (1.0)
Day 11 0.5  (1.0) 0  (0) 0.0  (0.0)
Last Visit 0.5  (1.0) 0  (0) 0.0  (0.0)
12.Secondary Outcome
Title Percentage of Participants Who Reported at Least One Occurrence of Suicidality, Suicidal Behavior and Suicidal Ideation on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Hide Description The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). The suicidal ideation intensity total score is the sum of intensity scores of 5 items (frequency, duration, controllability, deterrents, and reasons for ideation). The score of each intensity item ranges from 0 (none) to 5 (worst) which leads to the range of the total score from 0 to 25, with a higher score indicating a worse outcome. A missing score of any item resulted in a missing total score. If no suicidal ideation was reported, a score of 0 was given to the intensity scale. Last Visit is last scheduled post-baseline evaluation including early termination evaluation.
Time Frame Baseline to Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2- Brexpiprazole 1mg Cohort 3 Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Number
Unit of Measure: Percentage of participants
Suicidality 0 0 0
Suicidal behaviour 0 0 0
Suicidal Ideation 0 0 0
13.Secondary Outcome
Title Mean Change From Baseline in Positive and Negative Symptom Scale (PANSS) Total Score
Hide Description The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.
Time Frame Baseline to Day 6, 11 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety sample included participants that are administered at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2 - Brexpiprazole 1mg Cohort 3 - Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Day 6 -4.0  (7.4) 0.3  (4.0) -2.0  (3.9)
Day 11 -1.5  (5.2) 6.0  (11.1) -4.0  (10.5)
Last Visit -1.5  (5.2) 6.0  (11.1) -3.0  (8.7)
14.Secondary Outcome
Title Mean Change From Baseline in PANNS Positive Subscale Score
Hide Description The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.
Time Frame Baseline to Day 6, 11 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2- Brexpiprazole 1mg Cohort 3 Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Day 6 -0.8  (1.0) 0.0  (2.0) -0.8  (3.9)
Day 11 0.5  (1.0) 0.5  (6.1) -2.7  (7.5)
Last Visit 0.5  (1.0) 0.5  (6.1) -2.0  (6.3)
15.Secondary Outcome
Title Mean Change From Baseline in PANSS Negative Subscale Score
Hide Description The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.
Time Frame Baseline to Day 6, 11 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2- Brexpiprazole 1mg Cohort 3 Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received once 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Day 6 -2.5  (4.4) 1.0  (1.0) 0.3  (1.0)
Day 11 -1.5  (2.4) 0.5  (3.0) -0.3  (3.2)
Last Visit -1.5  (2.4) 0.5  (3.0) -0.3  (2.6)
16.Secondary Outcome
Title Mean Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score
Hide Description The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.
Time Frame Baseline to Day 6, 11 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2- Brexpiprazole 1mg Cohort 3 Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received once 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Day 6 0.3  (0.5) 0.0  (0.0) 0.8  (1.0)
Day 11 0.5  (1.0) 0.0  (0.0) 1.0  (1.0)
Last Visit 0.5  (1.0) 0.0  (0.0) 0.8  (1.0)
17.Secondary Outcome
Title Mean Change From Baseline in Clinical Global Impression-Improvement (CGI-I) Score
Hide Description The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at baseline. Response choices include: 0 = not assessed; 1 =very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 =minimally worse; 6 = much worse; and 7 = very much worse. Last Visit is the last scheduled post-baseline evaluation including early termination evaluation.
Time Frame Baseline to Day 6, 11 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1 - Brexpiprazole 4mg Cohort 2- Brexpiprazole 1mg Cohort 3 Brexpiprazole 4mg
Hide Arm/Group Description:
Participants in cohort 1 received 1-mg of brexpiprazole once daily on Days 1 to 3 and 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Participants in cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10.
Participants in cohort 3 received once 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Day 6 4.0  (0.0) 4.0  (0.0) 4.0  (0.0)
Day 11 3.5  (1.0) 3.8  (0.5) 2.7  (1.2)
Time Frame Adverse events were reported once the informed consent was signed, throughout the 10-day treatment period until the safety follow-up via telephone 30 (+2) days post-last dose of study medication.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1 - Brexpiprazole 4 mg Cohort 2 - Brexpiprazole 1 mg Cohort 3 - Brexpiprazole 4 mg
Hide Arm/Group Description Participants in cohort 1 received one 1-mg of brexpiprazole once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10. Participants in cohort 2 received one 1-mg tablet of brexpiprazole once daily on Days 1 to 10. Participants in cohort 3 received once 1- to 4-mg dose of brexpiprazole (at the study physician's discretion) once daily on Days 1 to 3 and one 4-mg tablet of brexpiprazole once daily on Days 4 to 10.
All-Cause Mortality
Cohort 1 - Brexpiprazole 4 mg Cohort 2 - Brexpiprazole 1 mg Cohort 3 - Brexpiprazole 4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1 - Brexpiprazole 4 mg Cohort 2 - Brexpiprazole 1 mg Cohort 3 - Brexpiprazole 4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/4 (0.00%)   0/4 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1 - Brexpiprazole 4 mg Cohort 2 - Brexpiprazole 1 mg Cohort 3 - Brexpiprazole 4 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   2/4 (50.00%)   3/4 (75.00%) 
Eye disorders       
Blepharospasm * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders       
Abdominal discomfort * 1  0/4 (0.00%)  2/4 (50.00%)  0/4 (0.00%) 
Abdominal pain * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Dental carries * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
Dyspepsia * 1  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%) 
General disorders       
Fatigue * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Malaise * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
Nervous system disorders       
Akathisia * 1  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%) 
Sedation * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Psychiatric disorders       
Agitation * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Vascular disorders       
Peripheral artery thrombosis * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Results Point of Contact
Name/Title: Global Medical Affairs
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
Phone: 800 562-3974
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01854944     History of Changes
Other Study ID Numbers: 331-09-219
First Submitted: May 7, 2013
First Posted: May 16, 2013
Results First Submitted: September 17, 2015
Results First Posted: February 4, 2016
Last Update Posted: February 4, 2016