## Protocol Section
### Identification Module
**NCT ID:** NCT01670279

**Brief Title:** Phase 1 Study to Assess the Safety/Tolerability of Brexpiprazole as Adjunctive Therapy in Elderly Subjects With Major Depressive Disorder

**Official Title:** A Phase 1, Multicenter, Randomized, Double-blind, Sequential Cohort, Placebo-controlled Trial to Assess the Safety and Tolerability of Ascending Multiple Oral Doses of Brexpiprazole as Adjunctive Therapy in the Treatment of Elderly Subjects With Major Depressive Disorder

#### Organization Study ID Info
**ID:** 331-12-291
#### Organization
**Class:** INDUSTRY
**Full Name:** Otsuka Pharmaceutical Development & Commercialization, Inc.
### Status Module
#### Completion Date
**Date:** 2013-05

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2016-02-04

**Type:** ESTIMATED

**Last Update Submit Date:** 2016-01-05

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2013-05

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2016-02-04

**Type:** ESTIMATED

**Results First Submit Date:** 2015-08-04

**Results First Submit QC Date:** 2016-01-05

#### Start Date
**Date:** 2012-07

**Status Verified Date:** 2016-01

#### Study First Post Date
**Date:** 2012-08-22
**Type:** ESTIMATED
**Study First Submit Date:** 2012-08-07
**Study First Submit QC Date:** 2012-08-21
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** H. Lundbeck A/S

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Otsuka Pharmaceutical Development & Commercialization, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study is to assess the safety and tolerability of ascending multiple oral doses of brexpiprazole as adjunctive therapy in the treatment of elderly subjects with MDD.

**Detailed Description:** This is a phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial in 3 sequential cohorts of elderly subjects (age 70 to 85 years old) with MDD. Brexpiprazole will be administered as an adjunct treatment to the current antidepressant therapy that the subject is receiving. Total individual subject duration is expected to be no more than 119 days (a 30-day screening period, a 14-day washout period, up to 45-day in-clinic treatment period, and a 30-day follow-up after the last dose of trial medication).

### Conditions Module

**Conditions:**

- Major Depressive Disorder

**Keywords:**

- Major Depressive Disorder (MDD)

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 18

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 14 day titration phase and two fixed dose phases. The first fixed dose phase is 14 days with a daily dose of 2mg brexpiprazole/placebo. The second fixed dose phase is 14 days with a daily dose of 3 mg brexpiprazole/placebo.

**Intervention Names:**

- Drug: Brexpiprazole

**Label:** Cohort 1

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 14 day titration phase and a 14 day fixed dose phase a daily dose of 3mg brexpiprazole/placebo.

**Intervention Names:**

- Drug: Brexpiprazole

**Label:** Cohort 2

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** 21 day titration phase and a 14 day fixed dose phase a daily dose of 3mg brexpiprazole/placebo.

**Intervention Names:**

- Drug: Brexpiprazole

**Label:** Cohort 3

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** Placebo

**Intervention Names:**

- Drug: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cohort 1

- Cohort 2

- Cohort 3

**Description:** up to 3mg oral dose once daily

**Name:** Brexpiprazole

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Safety and tolerability of brexpiprazole was noted to be primary outcome measure. Brexpiprazole was judged to be tolerated if at least 6 out of 8 (75%) of the participants in a test cohort tolerated the dose after 14 days of QD dosing at the end of the fixed dose phase based on the blinded data. Dose toleration was defined as follows: during the course of the trial, the participants did not experience any moderate or severe adverse events (AEs) or potentially clinically relevant changes from Baseline in laboratory values, vital signs, electrocardiogram (ECG) tracings, Columbia-Suicide Severity Rating Scale (C-SSRS), or extrapyramidal symptom (EPS) ratings, which were assessed as possibly related to the study drug, and would have warranted a dose decrease or discontinuation of the study drug. The safety and tolerability of brexpiprazole was defined by parameters: AEs, laboratory values, vital signs, ECG, C-SSRS, or EPS ratings, the results of each of the parameters reported separately.

**Measure:** Number of Participants Who Tolerated Brexpiprazole

**Time Frame:** 45 Days

**Description:** The AEs were one of the primary parameters to measure the safety and tolerability of individual participants. The AEs were captured for all participants from the time the ICF was signed until the end of the trial. AEs were measured throughout the 14-day titration and 28-day fixed dose phase until follow-up (30 \[±2\] days after last dose of study medication).

**Measure:** Number of AEs Reported.

**Time Frame:** Throughout the study, up to 119 days

**Description:** The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria.

**Measure:** Incidence of Laboratory Values of Potential Clinical Significance

**Time Frame:** Titration Day 7, Fixed dose Day 14 and 28 and Last Visit

**Description:** The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria.

**Measure:** Incidence of Vital Signs of Potential Clinical Significance

**Time Frame:** Baseline, Titration Day 1, 2, 7, 8, Fixed Days 1, 2, 14, 15, 28, 29, Early Termination and Last Visit.

**Description:** The measurement of ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, and QTcF that were identified based on pre-defined criteria.

**Measure:** Incidence of ECG Evaluations of Potential Clinical Significance

**Time Frame:** Titratrion Day 1 and 7, Fixed dose Day 1, 14, 28, Early Termination

**Description:** The physical examination evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in the following body systems: head, ears, eyes, nose, and throat; thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae.

**Measure:** Incidence of Physical Examination Evaluation of Potential Clinical Significance

**Time Frame:** Physical examination was performed at Screening, check-in, and discharge

**Description:** EPS was one of the primary parameters to measure the safety and tolerability of individual participants. 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.

**Measure:** Mean Change From Baseline to Study Completion in Simpson-Angus Scale (SAS) Total Score

**Time Frame:** End of Titration, Day 15, Day 29, Early Termination and Last visit

**Description:** EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The Barnes Akathisia Rating Scale was an EPS rating scale. The Barnes Akathisia Rating Scale was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia).

**Measure:** Mean Change From Baseline to Study Completion in Barnes Akathisia Global Score

**Time Frame:** End of Titration, Day 15, Day 29, Early Termination and Last visit

**Description:** EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The AIMS Scale was an EPS rating scale. The AIMS is a 12 item scale. 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.

**Measure:** Mean Change From Baseline to Study Completion in Abnormal Involuntary Movement Scale (AIMS) Rating Score.

**Time Frame:** End of Titration, Day 15, Day 29, Early Termination and Last visit

**Description:** The C-SSRS was one of the primary parameters to measure the safety and tolerability of individual participants. Suicidality was monitored during the trial using the C-SSRS. This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last trial visit.

**Measure:** Change From Baseline to Study Completion in C-SSRS Score.

**Time Frame:** Baseline, End of Titration, Fixed dose Day 14 and 28, Day 15 and 29, Early Termination, Last Visit

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Subjects who are able to provide written informed consent
* Ability to understand the nature of the trial and follow protocol requirements
* Male and female patients 70 to 85 years of age
* Subjects with normal or clinically stable findings on physical examination, medical history, clinical laboratory determinations, ECGs in relation to age
* BMI of 18 to 35 kg/m2.
* Stable subjects with a principal psychiatric diagnosis of MDD
* Subjects willing to discontinue all prohibited psychotropic and other prohibited medication

Exclusion Criteria:

* Sexually active males who are not practicing 2 different methods of birth control during the trial and for 30 days after the last dose of trial medication or who will not remain abstinent during the trial and for 30 days after the last dose
* Subjects who have had a vagus nerve stimulation device implanted or who have received ECT within 6 months of Screening
* Subjects with a current Axis I (DSM-IV-TR) diagnosis of:

  * Delirium, dementia, amnestic, or other cognitive disorder
  * Eating disorder (including anorexia nervosa or bulimia)
  * Obsessive-compulsive disorder
  * Panic disorder
  * Posttraumatic stress disorder or current or prior Axis I (DSM-IV-TR) diagnosis of Schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder or bipolar disorder not otherwise specified
* Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder
* Subjects experiencing hallucinations, delusions, or any psychotic symptomatology
* Subjects who have Active Suicidal Ideation with Some Intent to Act and whose most recent episode occurred within the last 6 months
* Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days
* Subjects with hypothyroidism or hyperthyroidism and/or an abnormal result for free T4 at Screening
* Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders
* Subjects with IDDM
* Subjects with uncontrolled hypertension (DBP \> 95 mmHg) or symptomatic hypotension
* Subjects with epilepsy, a history of epilepsy, or a history of seizure
* Subjects with a positive drug screen for cocaine or other drugs of abuse
* The following laboratory test and ECG results are exclusionary:

  1. Platelets ≤ 75,000/mm3
  2. Hemoglobin ≤ 9 g/dL
  3. Neutrophils, absolute ≤ 1000/mm3
  4. AST \> 3 × upper limit of normal
  5. ALT \> 3 × upper limit of normal
  6. Creatinine ≥ 2 mg/dL
  7. HbA1c ≥ 7%
  8. QTcF ≥ 450 msec
* Treatment with a MAOI within the 2 weeks prior to the first dose of trial medication
* Use of benzodiazepines and/or hypnotics within 1 week prior the first dose of trial medication
* Use of oral neuroleptics within 30 days prior to or long-acting approved neuroleptics ≤ 1 full cycle plus 14 days prior to the first dose of trial medication on Day 1
* Prohibited concomitant medications used prior to randomization or anticipated need for such medications during the trial
* Subjects who would be likely to require prohibited concomitant therapy during the trial
* Subjects who received brexpiprazole in any prior clinical trial
* Subjects with a history of neuroleptic malignant syndrome
* Subjects with a history of true allergic response to more than 1 class of medications
* Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
* Subjects who participated in a clinical trial within the last 180 days or who participated in more than 2 clinical trials within the past year.

**Maximum Age:** 85 Years

**Minimum Age:** 70 Years

**Sex:** ALL

**Standard Ages:**

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Kissimmee

**Country:** United States

**Facility:** Accurate Clinical Trials

**State:** Florida

**Location 2:**

**City:** Miami

**Country:** United States

**Facility:** Miami Jewish Health System

**State:** Florida

**Location 3:**

**City:** St. Louis

**Country:** United States

**Facility:** St. Louis Clinical Trials

**State:** Missouri

**Location 4:**

**City:** Philadelphia

**Country:** United States

**Facility:** CRI Lifetree- Philadelphia Research Center

**State:** Pennsylvania

#### Overall Officials

**Official 1:**

**Affiliation:** Otsuka Pharmaceutical Development & Commercialization, Inc.

**Name:** James M. Youakim, MD

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000019964

- Term: Mood Disorders

- ID: D000001523

- Term: Mental Disorders

- ID: D000001526

- Term: Behavioral Symptoms

### Condition Browse Module - Browse Branches

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7058

- Name: Depression

- Relevance: HIGH

- As Found: Depressive Disorder

- ID: M7061

- Name: Depressive Disorder

- Relevance: HIGH

- As Found: Depressive Disorder

- ID: M7060

- Name: Depressive Disorder, Major

- Relevance: HIGH

- As Found: Major Depressive Disorder

- ID: M21835

- Name: Mood Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4818

- Name: Behavioral Symptoms

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003866

- Term: Depressive Disorder

- ID: D000003863

- Term: Depression

- ID: D000003865

- Term: Depressive Disorder, Major

### Intervention Browse Module - Ancestors

- ID: D000018490

- Term: Serotonin Agents

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018491

- Term: Dopamine Agonists

- ID: D000015259

- Term: Dopamine Agents

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: CaAg

- Name: Cardiotonic Agents

### Intervention Browse Module - Browse Leaves

- ID: M293045

- Name: Brexpiprazole

- Relevance: HIGH

- As Found: Urban

- ID: M15512

- Name: Serotonin

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7473

- Name: Dopamine

- Relevance: LOW

- As Found: Unknown

- ID: M20595

- Name: Dopamine Agonists

- Relevance: LOW

- As Found: Unknown

- ID: M17962

- Name: Dopamine Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000591922

- Term: Brexpiprazole

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

**Description:** Participants who had received at least one dose of study medication were included in safety analysis.

#### Event Groups

**Group ID:** EG000

**Title:** Brexpiprazole-Cohort 1

**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.

**ID:** EG000

**Other Num Affected:** 6

**Other Num at Risk:** 6

**Serious Number At Risk:** 6

**Title:** Brexpiprazole-Cohort 1

**Group ID:** EG001

**Title:** Brexpiprazole-Cohort 2

**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.

**ID:** EG001

**Other Num Affected:** 6

**Other Num at Risk:** 6

**Serious Number At Risk:** 6

**Title:** Brexpiprazole-Cohort 2

**Group ID:** EG002

**Title:** Placebo

**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.

**ID:** EG002

**Other Num Affected:** 1

**Other Num at Risk:** 5

**Serious Number At Risk:** 5

**Title:** Placebo

**Frequency Threshold:** 0

#### Other Events

**Term:** Atrioventricular block first degree

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Cardiac disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Hyperprolactinaemia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Endocrine disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Diarrhoea

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Dyspepsia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Nausea

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Cardiac murmur

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA 15.0

**Term:** Electrocardiogram QT prolonged

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA 15.0

**Term:** Weight increased

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA 15.0

**Term:** Dizziness

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Headache

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Tremor

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Nervous system disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Insomnia

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Psychiatric disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Pollakiuria

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Renal and urinary disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Oropharyngeal pain

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Arthritis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Back pain

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Pain in extremity

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Upper respiratory tract infection

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Infections and infestations

**Source Vocabulary:** MedDRA 15.0

**Term:** Oedema peripheral

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Constipation

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Dental caries

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Gastrooesophageal reflux disease

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Vomiting

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Eye pruritis

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Eye disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Dry eye

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Eye disorders

**Source Vocabulary:** MedDRA 15.0

**Term:** Blood pressure

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** MedDRA 15.0

**Time Frame:** AEs were captured for all participants from the signing of the informed consent and were measured throughout the 14-day titration period, 28-day fixed dose period until follow-up (30 [±2] days after last dose of study medication).

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 6

**Group ID:** BG001

**Value:** 7

**Group ID:** BG002

**Value:** 5

**Group ID:** BG003

**Value:** 18

**Units:** Participants

### Group

**ID:** BG000

**Title:** Brexpiprazole-Cohort 1

**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.

### Group

**ID:** BG001

**Title:** Brexpiprazole-Cohort 2

**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.

### Group

**ID:** BG002

**Title:** Placebo

**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.

### Group

**ID:** BG003

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 4.0

**Value:** 73.2

#### Measurement

**Group ID:** BG001

**Spread:** 5.3

**Value:** 76.0

#### Measurement

**Group ID:** BG002

**Spread:** 1.5

**Value:** 72.6

#### Measurement

**Group ID:** BG003

**Spread:** 4.2

**Value:** 74.1

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 4

#### Measurement

**Group ID:** BG001

**Value:** 5

#### Measurement

**Group ID:** BG002

**Value:** 4

#### Measurement

**Group ID:** BG003

**Value:** 13

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 2

#### Measurement

**Group ID:** BG001

**Value:** 2

#### Measurement

**Group ID:** BG002

**Value:** 1

#### Measurement

**Group ID:** BG003

**Value:** 5

**Category Title:** Male

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** Years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
## Results Section - More Information Module
### Certain Agreement
### Limitations and Caveats
**Description:** Cohort 3 was not initiated based on the safety/tolerability results from Cohorts 1 and 2.
### Point of Contact
**Organization:** Otsuka Pharmaceutical Development and Commercialization, Inc.
**Phone:** 800 562-3974
**Title:** Global Medical Affairs
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
### Outcome Measure 3
### Outcome Measure 4
### Outcome Measure 5
### Outcome Measure 6
### Outcome Measure 7
### Outcome Measure 8
### Outcome Measure 9
### Outcome Measure 10
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 7
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 5
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 12
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 33
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
#### Outcome Measure 4
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
#### Outcome Measure 5
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
**Title:** 
#### Outcome Measure 6
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
#### Outcome Measure 7
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.5
- **Upper Limit:** 
- **Value:** -0.3
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.8
- **Upper Limit:** 
- **Value:** -0.5
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.8
- **Upper Limit:** 
- **Value:** -1.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** N=0, data not collected.
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.4
- **Upper Limit:** 
- **Value:** 0.2
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.7
- **Upper Limit:** 
- **Value:** -1.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.4
- **Upper Limit:** 
- **Value:** -0.3
- **Comment:** N=0, data not collected.
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** N=0, data not collected.
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** N=1, standard deviation is not applicable.
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** -1.0
- **Comment:** N=1, standard deviation is not applicable.
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** 0.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.4
- **Upper Limit:** 
- **Value:** -0.2
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.6
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.9
- **Upper Limit:** 
- **Value:** -0.6
**Title:** 
#### Outcome Measure 8
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.4
- **Upper Limit:** 
- **Value:** -0.2
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.6
- **Upper Limit:** 
- **Value:** -0.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** N=0, data not collected.
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.7
- **Upper Limit:** 
- **Value:** -0.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** N=0, data not collected.
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.7
- **Upper Limit:** 
- **Value:** -0.5
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** N=0, data not collected.
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** N=1, standard deviation is not applicable.
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** N=1, standard deviation is not applicable.
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** 0.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.5
- **Upper Limit:** 
- **Value:** -0.4
**Title:** 
#### Outcome Measure 9
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.4
- **Upper Limit:** 
- **Value:** 0.2
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** N=0, data not collected.
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** N=0, data not collected.
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** N=0, data not collected.
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** NA
- **Comment:** N=1, standard deviation is not applicable.
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** N=1, standard deviation is not applicable.
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** NA
- **Upper Limit:** 
- **Value:** 0.0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.0
- **Upper Limit:** 
- **Value:** 0.0
**Title:** 
#### Outcome Measure 10
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 0
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** Safety and tolerability of brexpiprazole was noted to be primary outcome measure. Brexpiprazole was judged to be tolerated if at least 6 out of 8 (75%) of the participants in a test cohort tolerated the dose after 14 days of QD dosing at the end of the fixed dose phase based on the blinded data. Dose toleration was defined as follows: during the course of the trial, the participants did not experience any moderate or severe adverse events (AEs) or potentially clinically relevant changes from Baseline in laboratory values, vital signs, electrocardiogram (ECG) tracings, Columbia-Suicide Severity Rating Scale (C-SSRS), or extrapyramidal symptom (EPS) ratings, which were assessed as possibly related to the study drug, and would have warranted a dose decrease or discontinuation of the study drug. The safety and tolerability of brexpiprazole was defined by parameters: AEs, laboratory values, vital signs, ECG, C-SSRS, or EPS ratings, the results of each of the parameters reported separately.
**Parameter Type:** NUMBER
**Population Description:** Tolerability assessed in phase 1 trial in healthy participants (18-45 years) with MDD as adjunct therapy to ADTs; the efficacy assessed in phase 3 trials in participants (18-65 years) with MDD as adjunct therapy to ADTs. Thus, safety/tolerability of brexpiprazole in participants (\>65 years) with MDD as adjunct therapy to ADTs was not characterized.
**Reporting Status:** POSTED
**Time Frame:** 45 Days
**Title:** Number of Participants Who Tolerated Brexpiprazole
**Type:** PRIMARY
**Unit of Measure:** participants
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 2
**Description:** The AEs were one of the primary parameters to measure the safety and tolerability of individual participants. The AEs were captured for all participants from the time the ICF was signed until the end of the trial. AEs were measured throughout the 14-day titration and 28-day fixed dose phase until follow-up (30 \[±2\] days after last dose of study medication).
**Parameter Type:** NUMBER
**Population Description:** The safety dataset included all randomized participants who received at least one dose of study medication.
**Reporting Status:** POSTED
**Time Frame:** Throughout the study, up to 119 days
**Title:** Number of AEs Reported.
**Type:** PRIMARY
**Unit of Measure:** Events
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 3
**Description:** The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria.
**Parameter Type:** NUMBER
**Population Description:** The safety dataset included all randomized participants who received at least one dose of study medication.
**Reporting Status:** POSTED
**Time Frame:** Titration Day 7, Fixed dose Day 14 and 28 and Last Visit
**Title:** Incidence of Laboratory Values of Potential Clinical Significance
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 4
**Description:** The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria.
**Parameter Type:** NUMBER
**Population Description:** The safety dataset included all randomized participants who received at least one dose of study medication.
**Reporting Status:** POSTED
**Time Frame:** Baseline, Titration Day 1, 2, 7, 8, Fixed Days 1, 2, 14, 15, 28, 29, Early Termination and Last Visit.
**Title:** Incidence of Vital Signs of Potential Clinical Significance
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 5
**Description:** The measurement of ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, and QTcF that were identified based on pre-defined criteria.
**Parameter Type:** NUMBER
**Population Description:** The safety dataset included all randomized participants who received at least one dose of study medication.
**Reporting Status:** POSTED
**Time Frame:** Titratrion Day 1 and 7, Fixed dose Day 1, 14, 28, Early Termination
**Title:** Incidence of ECG Evaluations of Potential Clinical Significance
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 6
**Description:** The physical examination evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in the following body systems: head, ears, eyes, nose, and throat; thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae.
**Parameter Type:** NUMBER
**Population Description:** Safety Sample was analyzed. Any clinically significant condition present at the post-treatment physical examination that was not present at the baseline examination was documented as an adverse event and followed to a satisfactory conclusion. There were no clinically significant physical examination findings reported in this study.
**Reporting Status:** POSTED
**Time Frame:** Physical examination was performed at Screening, check-in, and discharge
**Title:** Incidence of Physical Examination Evaluation of Potential Clinical Significance
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 7
**Description:** EPS was one of the primary parameters to measure the safety and tolerability of individual participants. 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.
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Population Description:** Safety Sample includes all randomized participants who receive at least one dose of study medication.
**Reporting Status:** POSTED
**Time Frame:** End of Titration, Day 15, Day 29, Early Termination and Last visit
**Title:** Mean Change From Baseline to Study Completion in Simpson-Angus Scale (SAS) Total Score
**Type:** PRIMARY
**Unit of Measure:** Units on a scale
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 8
**Description:** EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The Barnes Akathisia Rating Scale was an EPS rating scale. The Barnes Akathisia Rating Scale was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia).
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Population Description:** Safety Sample includes all randomized participants who receive at least one dose of study medication.
**Reporting Status:** POSTED
**Time Frame:** End of Titration, Day 15, Day 29, Early Termination and Last visit
**Title:** Mean Change From Baseline to Study Completion in Barnes Akathisia Global Score
**Type:** PRIMARY
**Unit of Measure:** Units on a scale
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 9
**Description:** EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The AIMS Scale was an EPS rating scale. The AIMS is a 12 item scale. 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.
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Population Description:** Safety Sample includes all randomized participants who receive at least one dose of study medication.
**Reporting Status:** POSTED
**Time Frame:** End of Titration, Day 15, Day 29, Early Termination and Last visit
**Title:** Mean Change From Baseline to Study Completion in Abnormal Involuntary Movement Scale (AIMS) Rating Score.
**Type:** PRIMARY
**Unit of Measure:** Units on a scale
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
#### Outcome Measure 10
**Description:** The C-SSRS was one of the primary parameters to measure the safety and tolerability of individual participants. Suicidality was monitored during the trial using the C-SSRS. This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last trial visit.
**Parameter Type:** NUMBER
**Population Description:** Safety Sample includes all randomized participants who receive at least one dose of study medication.
**Reporting Status:** POSTED
**Time Frame:** Baseline, End of Titration, Fixed dose Day 14 and 28, Day 15 and 29, Early Termination, Last Visit
**Title:** Change From Baseline to Study Completion in C-SSRS Score.
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** OG000
**Title:** Brexpiprazole-Cohort 1
##### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** OG001
**Title:** Brexpiprazole-Cohort 2
##### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** OG002
**Title:** Placebo
### Participant Flow Module
#### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
**ID:** FG000
**Title:** Brexpiprazole-Cohort 1
#### Group
**Description:** In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
**ID:** FG001
**Title:** Brexpiprazole-Cohort 2
#### Group
**Description:** In the titration phase, participants were to receive 0.5 mg brexpiprazole or placebo QD for 7 days, followed by 1 mg brexpiprazole or placebo QD for 7 days, and then 2 mg brexpiprazole or placebo QD for 7 days. In the fixed dose phase, participants were to receive 3 mg brexpiprazole or placebo QD for 14 days. However, Cohort 3 was not conducted due to safety and tolerability results from Cohorts 1 and 2.
**ID:** FG002
**Title:** Brexpiprazole-Cohort 3
#### Group
**Description:** In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
**ID:** FG003
**Title:** Placebo
#### Period
**Title:** Overall Study
##### Withdraw
**Type:** Adverse Event
###### Reason
**Group ID:** FG000
**Number of Subjects:** 0
###### Reason
**Group ID:** FG001
**Number of Subjects:** 1
###### Reason
**Group ID:** FG002
**Number of Subjects:** 0
###### Reason
**Group ID:** FG003
**Number of Subjects:** 0
##### Withdraw
**Type:** Physician Decision
###### Reason
**Group ID:** FG000
**Number of Subjects:** 0
###### Reason
**Group ID:** FG001
**Number of Subjects:** 1
###### Reason
**Group ID:** FG002
**Number of Subjects:** 0
###### Reason
**Group ID:** FG003
**Number of Subjects:** 0
##### Withdraw
**Type:** Participant met withdrawal criteria
###### Reason
**Group ID:** FG000
**Number of Subjects:** 0
###### Reason
**Group ID:** FG001
**Number of Subjects:** 0
###### Reason
**Group ID:** FG002
**Number of Subjects:** 0
###### Reason
**Group ID:** FG003
**Number of Subjects:** 1
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 6
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 7
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG003
**Number of Subjects:** 5
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 6
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 5
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG003
**Number of Subjects:** 4
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 2
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG003
**Number of Subjects:** 1
**Pre-Assignment Details:** The study included a 30-day screening period, a 14-day washout period, up to 45-day inpatient treatment period (titration: received brexpiprazole or placebo once daily \[QD\] for 14 or 21 days and fixed dose phase: received assigned fixed dose for 14 or 28 days), and a 30-day follow-up after the last dose of study drug.
**Recruitment Details:** This was a phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial planned in 3 sequential cohorts of elderly participants (70 to 85 years old) with major depressive disorder (MDD). Brexpiprazole was administered as an adjunct treatment to the current antidepressant therapy that the participant received.
**Has Results:** True