Safety and Tolerability of Open-Label Flexible-dose Brexpiprazole as Maintenance Treatment in Adolescents With Schizophrenia

A Long-term, Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Flexible-Dose Brexpiprazole as Maintenance Treatment in Adolescents (13-17 Years Old) With Schizophrenia

To further characterize the long-term safety and tolerability of brexpiprazole in adolescents with schizophrenia

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Brexpiprazole

Detailed Description

This is a long-term, multicenter, open-label trial designed to examine the long-term safety and tolerability of brexpiprazole in adolescent participants (ages 13-17) with a DSM-5 diagnosis of schizophrenia.

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Nice, France, 06200
    • Clinical Research Site #321
• Italy
  • Naples, Italy, 80131
    • Clinical Research Site #283
• Mexico
  • Durango, Mexico, 34000
    • Clinical Research Site #168
  • Guanajuato
    • León, Guanajuato, Mexico, 37000
      • Clinical Research Site #163
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • Clinical Research Site #165
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64310
      • Clinical Research Site #171
    • Monterrey, Nuevo León, Mexico, 64710
      • Clinical Research Site #160
  • San Luis Potosí
    • San Luis Potosí City, San Luis Potosí, Mexico, 78213
      • Clinical Research Site #170
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80230
      • Clinical Research Site #161
  • Yucatán
    • Mérida, Yucatán, Mexico, 97070
      • Clinical Research Site #166
• Poland
  • Poznan, Poland, 60-744
    • Clinical Research Site #260
  • Poznan, Poland, 61-485
    • Clinical Research Site #272
  • Wałbrzych, Poland, 58-309
    • Clinical Research Site #270
  • Wroclaw, Poland, 54-617
    • Clinical Research Site #267
  • Dolnyslask
    • Tyniec Mały, Dolnyslask, Poland, 55-040
      • Clinical Research Site #263
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-879
      • Clinical Research Site #266
  • Polorskie
    • Gdansk, Polorskie, Poland, 80-542
      • Clinical Research Site #269
• Romania
  • Bucharest, Romania, 041914
    • Clinical Research Site #244
  • Cluj-Napoca, Romania, 400660
    • Clinical Research Site #241
  • Iași, Romania, IS700282
    • Clinical Research Site #243
  • Timișoara, Romania, 300329
    • Clinical Research Site #242
• Russia
  • Moscow, Russia, 127083
    • Clinical Research Site #545
  • Saint Petersburg, Russia, 192019
    • Clinical Research Site #541
  • Saint Petersburg, Russia, 197341
    • Clinical Research Site #540
  • Yaroslavl, Russia, 150003
    • Clinical Research Site #544
  • Primorsky District
    • Arkhangelsk, Primorsky District, Russia, 163530
      • Clinical Research Site #542
  • Stavropolskiy Kray
    • Stavropol, Stavropolskiy Kray, Russia, 355038
      • Clinical Research Site #543
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Research Site #500
  • Belgrade, Serbia, 11000
    • Clinical Research Site #504
  • Kragujevac, Serbia, 34000
    • Clinical Research Site #503
  • Niš, Serbia, 18000
    • Clinical Research Site #502
  • Novi Sad, Serbia, 21000
    • Clinical Research Site #501
• Spain
  • Malaga
    • Torremolinos, Malaga, Spain, 29620
      • Clinical Research Site #224
• Ukraine
  • Dnipro, Ukraine, 49027
    • Clinical Research Site #527
  • Kharkiv, Ukraine, 61068
    • Clinical Research Site #523
  • Kharkiv, Ukraine, 61153
    • Clinical Research Site #521
  • Kherson, Ukraine, 73488
    • Clinical Research Site #522
  • Lviv, Ukraine, 79021
    • Clinical Research Site #520
  • Ternopil, Ukraine, 46027
    • Clinical Research Site #525
  • Poltava Oblast
    • Poltava, Poltava Oblast, Ukraine, 36013
      • Clinical Research Site #526
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Clinical Research Site #101
  • California
    • Anaheim, California, United States, 92805
      • Clinical Research Site #128
    • Culver City, California, United States, 90230
      • Clinical Research Site #105
    • Long Beach, California, United States, 90807
      • Clinical Research Site #103
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Clinical Research Site #136
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Clinical Research Site #148
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Clinical Research Site #138
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Clinical Research Site #124
  • New York
    • New York, New York, United States, 10036
      • Clinical Research Site #130
    • Rochester, New York, United States, 14618
      • Clinical Research Site #100
  • North Carolina
    • Kinston, North Carolina, United States, 28501
      • Clinical Research Site #121
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Clinical Research Site #133
    • Garfield Heights, Ohio, United States, 44125
      • Clinical Research Site #113
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Clinical Research Site #102
    • Tulsa, Oklahoma, United States, 74136
      • Clinical Research Site #135
  • Texas
    • Frisco, Texas, United States, 75034
      • Clinical Research Site #140
  • Washington
    • Everett, Washington, United States, 98201
      • Clinical Research Site #108

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male & female subjects 13-17 years of age, inclusive.
• Subjects who turn 18 during trial 331-10-234 are permitted in this trial.
• Subjects with a current primary diagnosis of schizophrenia, as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria and confirmed by the K-SADS-PL completed at time of entry into Trial 331-10-234. For de novo subjects who did not participate in Trial 331-10-234, the initial diagnosis of schizophrenia must be made and documented, and the diagnosis confirmed by the K-SADS-PL at screening.
• Subjects who, in the investigator's judgment, require treatment with antipsychotic medication(s).

Exclusion Criteria:

• Subjects with a DSM-5 diagnosis other than schizophrenia that has been the primary focus of treatment within 3 months of screening
• Subjects with a clinical presentation or history that is consistent with delirium, dementia, amnesia, or other cognitive disorders; subjects with psychotic symptoms that are better accounted for by another general medical condition(s) or direct effect of a substance (e.g., medication, illicit drug use).
• History of failure of clozapine treatment or response to clozapine treatment only.
• History of neuroleptic malignant syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: De Novo (Conversion Period); 1-3 milligrams/day (mg/day) brexpiprazole for 1 to 4 weeks	Drug: Brexpiprazole; Once daily, oral tablets; Other Names: OPC-34712
Experimental: Prior and Current Brexpiprazole (Open-label Treatment Period); 1-4 mg/day brexpiprazole; Start at 0.5 mg/day, titrate and maintain between 1mg/day to max of 4 mg/day	Drug: Brexpiprazole; Once daily, oral tablets; Other Names: OPC-34712
Experimental: Prior Aripiprazole and Current Brexpiprazole (Open-label Treatment Period); 1-4 mg/day brexpiprazole; Start at 0.5 mg/day, titrate and maintain between 1mg/day to max of 4 mg/day	Drug: Brexpiprazole; Once daily, oral tablets; Other Names: OPC-34712
Experimental: Prior Placebo and Current Brexpiprazole (Open-label Treatment Period); 1-4 mg/day brexpiprazole; Start at 0.5 mg/day, titrate and maintain between 1mg/day to max of 4 mg/day	Drug: Brexpiprazole; Once daily, oral tablets; Other Names: OPC-34712
Experimental: De Novo (Open-label Treatment Period); 1-4 mg/day brexpiprazole; Start at 0.5 mg/day, titrate and maintain between 1mg/day to max of 4 mg/day	Drug: Brexpiprazole; Once daily, oral tablets; Other Names: OPC-34712

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with the study treatment.	From the first dose of study drug (including the conversion period and the open-label treatment period in the current study) up to 21 days after the last dose of study drug (up to approximately 25.6 months).
Number of Participants With Serious Treatment Emergent Adverse Events (TEAEs)	An AE is defined as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with the study treatment. A serious adverse event (SAE) is any AE occurring at any dose that results in death, life-threatening experience, persistent or significant disability/incapacity, in-patient hospitalization or prolongs hospitalization or congenital anomaly/birth defect. A serious TEAE is defined as an AE that occurred or worsened after the first dose of study treatment up until 30 days after the last dose.	From the first dose of study drug (including the conversion period and the open-label treatment period in the current study) up to 21 days after the last dose of study drug (up to approximately 25.6 months).
Number of Participants Who Discontinued the Trial Due to AEs	An AE is defined as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with the study treatment. Participants who discontinued the trial due to AEs were recorded.	From the first dose of study drug (including the conversion period and the open-label treatment period in the current study) up to 21 days after the last dose of study drug (up to approximately 25.6 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Laboratory Tests (Parameters Assessed in Units Per Liter)	Clinical laboratory assessments included clinical chemistry (alanine aminotransferase [ALT], alkaline phosphatase, aspartate aminotransferase [AST], creatinine phosphokinase (CPK), gamma glutamyl transferase, lactate dehydrogenase.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Laboratory Tests (Parameters Assessed in Milligrams Per Deciliter)	Clinical laboratory assessments included clinical chemistry (bilirubin, urea nitrogen, calcium, glucose, cholesterol including low-density lipoprotein (LDL-C), creatinine, Triglycerides [TG]).	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Laboratory Tests (Parameters Assessed in Percentage)	Clinical laboratory assessments of HbA1c are reported in this outcome measure.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Laboratory Tests (Parameters Assessed in Million Cells Per Microliter)	Clinical laboratory assessments included hematology including the red blood cell count (RBC Count).	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Clinical Laboratory Tests (Parameters Assessed in Thousand Cells Per Microliter)	Clinical laboratory assessments included hematology (basophils, eosinophils, neutrophils, leukocytes, lymphocytes, white blood cell (WBC) count, platelets).	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Laboratory Tests (Parameters That Were Unitless)	Clinical laboratory assessments of pH are reported in this outcome measure.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Laboratory Tests (Parameters Assessed in Nanograms Per Milliliter)	Clinical laboratory assessments included prolactin for both males and females.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Laboratory Tests (Parameters Assessed in Milliequivalents Per Liter)	Clinical laboratory assessments including chloride and potassium are reported in this outcome measure.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Tests	Laboratory assessments included hematology, chemistry, and urinalysis. Abnormality criteria included: In mg/dL [high bilirubin≥2.0, low calcium≤8.2, high cholesterol fasting≥240, HDL-C, Fasting<40 male(M)/ < 50 female(F); LDL-C, fasting≥160, high glucose, fasting≥100, non-fasting≥200 high TG, fasting≥150, high urate≥8.5 F/≥10.5 M, high protein urine≥2 units increase]; high creatine kinase(units per liter [U/L])>3xupper limit of normal (ULN)]; high eosinophils/leukocytes ≥10%;ALT>3×ULN; in mEq/L [Cl≤ 90; potassium≤ 2.5; sodium low≤ 126, high ≥156]; platelets≤75000/mm3; hemoglobin≤11g/dL M/≤ 9.5 F; glucose, urine≥2 units inc.; casts≥2 units inc.; hematocrit≤37% and decrease of≥3% points, M/≤ 32% and ≥3% points dec.,F. Number of participants with clinically significant laboratory test abnormalities were reported as per criteria defined in protocol. The categories with at least 1 participant with clinically significant abnormalities are reported.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Vital Signs (Parameters Assessed in Beats Per Minute)	Vital sign measurements included pulse rate assessed in beats per minute in standing and supine position.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Vital Signs (Parameters Assessed in Millimeters of Mercury)	Vital sign measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Blood pressure measurements were made in the supine and standing positions after the participant has been in each position at least 3 minutes.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Vital Signs (Parameters Assessed in Centimeters)	Vital sign measurements included height assessed in centimeters.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Vital Signs (Parameters Assessed in Kilograms)	Vital sign measurements included weight assessed in kilograms.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Vital Signs (Parameters Assessed in Celsius)	Vital sign measurements included temperature assessed in celsius.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Vital Signs (Parameters Assessed in Z-Score)	Vital sign measurements- Z-score for body weight (BW), height, and BMI. To adjust for normal growth, z-scores were derived, which normalize for the natural growth of pediatric patients and adolescents. Z-score was calculated as the deviation of the participant's each parameter from the mean for the respective parameter of the reference population divided by the standard deviation (SD) for the reference population. Z-score-0 represents the population mean for the respective parameter. Positive Z-scores-values above the mean, negative Z-scores indicate values below the mean. BW and BMI: Higher Z-scores-Potential overweight/obesity (worse outcome if excessive). Lower Z-scores -Underweight (worse outcome if extreme). Height: Higher Z-scores-Taller than average (neutral unless clinically relevant). Lower Z-scores → Short stature (may indicate growth issues). Z ≥ +2-Above normal range (e.g., overweight or obesity for BMI). Z ≤ -2-Below normal range (e.g., underweight or short stature).	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Vital Signs (Parameters Assessed in Kilograms Per Meter Square)	Vital sign measurements included body mass index (BMI).	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Number of Participants With Clinically Significant Abnormalities in Vital Signs	Vital sign measurements included SBP, and DBP, pulse rate, body temperature, body weight, BMI, and height. Vital sign measurements included pulse rate in supine and standing positions (low: <50 beats per minute [bpm] and decrease ≥15 bpm; High: >120 bpm and increase ≥15 bpm), SBP in supine and standing positions (low: <110 mmHg and decrease ≥20 mmHg; High: >120 mmHg and increase ≥20 mmHg), DBP in supine and standing positions (low: <60 mmHg and decrease ≥15 mmHg; High: >80 mmHg and increase ≥15 mmHg), weight in kg (low: ≥7% decrease; High: ≥7% increase), orthostatic hypotension, (≥20mmHg decrease in SBP or ≥10 mmHg in DBP in heart rate from supine to standing). Number of participants with clinically significant abnormalities in vital signs were reported as per criteria defined in protocol. The categories with at least one participant with clinically significant abnormalities in vital signs are reported.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in Electrocardiogram (ECG) (Parameters Assessed in Milliseconds)	12-lead ECG recordings were obtained for parameters including PR interval, QRS duration, QT interval, QTcB [QT interval as corrected for heart rate by Bazett's formula] interval, QTcF [QT interval as corrected for heart rate by Fridericia's formula] interval, QTcN [QT interval corrected for heart rate by the FDA Neuropharm] interval, and RR interval.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in ECG Parameters (Parameters Assessed in Beats Per Minute)	Twelve-lead ECG recordings were obtained for parameters including mean heart rate.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Number of Participants With Clinically Significant Abnormalities in ECG Parameters	12-lead ECG recordings were obtained for certain parameters and the 12-lead ECG abnormality criteria included bradycardia ≤ 50 bpm and decrease ≥15 bpm; sinus bradycardia ≤ 50 bpm and decrease of ≥ 15 bpm, supraventricular premature beat (SVPB)-not present at baseline and present post baseline, ventricular premature beat (VPB)- not present at baseline and present post baseline; and primary (1°) atrioventricular (AV) block (PR ≥200 milliseconds [msec] and increase of ≥50 msec, right bundle-branch block (RBBB) and symmetrical T-wave inversion (Sym T Wave Inv) - both not present at baseline and present post baseline; Increase in QTc-QTcF ≥ 450 msec for males, ≥ 470 msec for females. Number of participants with clinically significant ECG abnormalities was reported as per the criteria defined in the protocol. The categories with at least 1 participant with clinically significant ECG abnormalities are reported.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline on the Abnormal Involuntary Movement Scale (AIMS) Total Score	The AIMS assessment consists of 12 items rating the involuntary movements: Facial and oral movements (4 items), extremity movements (2 items), and trunk movements (1 item) were observed unobtrusively while the participant is at rest and the investigator also made global judgments on the participant's dyskinesias (2 items), and dental status (2 items). Severity of each item was rated on a 5-point scale, with a score of 0 (absence of symptoms) to 4 (severe condition). Total Score is the sum of the scores of all 12 items, ranging from 0 to 48, higher scores indicate severe condition. A negative change reflects an improvement or reduction in the severity of abnormal movements.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline on the Simpson-Angus Scale (SAS) Total Score	The SAS 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). Each item is rated on a 5-point scale, with a score of zero representing absence of symptoms, and a score of 4 representing a severe condition. The SAS Total Score is the sum of the scores for all 10 items, ranging from 0-40. A negative change reflects an improvement or reduction in Parkinsonism severity.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Change From Baseline in the Barnes Akathisia Rating Scale (BARS) Total Score	The BARS score is based only on the item of "Global Clinical Assessment of Akathisia". The BARS consists of 4 items related to akathisia as follows. Item 1: objective observation of akathisia by the investigator; Item 2: subjective feelings of restlessness by the participant; Item 3: subjective distress due to akathisia; and Item 4: global clinical assessment of akathisia. The first 3 items will be rated on a 4-point Likert scale from 0 to 3, with 0 representing absence of symptoms and 3 representing a severe condition. The BARS global clinical assessment score refers to the ratings from the 4th item Global Clinical Assessment of Akathisia, which is a 6-point Likert scale from 0 to 5, with 0 representing absence of symptoms and 5 representing severe akathisia. Total score is the sum of the scores of all 4 items, ranging from 0 to 14. Higher score indicates severe akathisia. A negative change from baseline reflects improvement or reduction in the severity of akathisia symptoms.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Number of Participants With At Least One Occurrence of Suicidal Behavior or Suicidal Ideation as Recorded on Columbia-Suicide Severity Rating Scale (C-SSRS)	C-SSRS is a scale used to report at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any of the following items: actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior. The suicidal ideation 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) and the total score ranges from 0 to 25. Lower scores indicate improvement.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Number of Participants With Psychotropic Side Effects as Assessed by Udvalg for Kliniske Undersogelser (UKU) Rating Scale	The UKU rating scale is a semi-structured interview used to assess the side effects of participants being treated with antipsychotic drugs. Each item (i.e., each symptom) of the UKU side effects is defined by the means of a 4-point-scale (0-1-2-3) if it is assessed in psychic, autonomic (auto), neurologic, other categories. In general, Degree 0 means "doubtfully or not present (NP)", and Degrees 1, 2, and 3 indicate that the symptom is present to a mild, moderate or severe degree, respectively.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Number of Participants With at Least One Occurrence of Cognitive Adverse Effects Assessed by New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT)	The NY-AACENT is used to detect changes in cognitive function for neurological or psychiatric problems, specifically created to be used in pediatric population (ages 12 -17), but could be used with other age groups, as appropriate. Each of the 7 items is derived from the 7 domains as follows: Working Memory, Attention/Vigilance, Verbal Learning/Memory, Visual Learning/Memory, Reasoning and Problem Solving, Speed of Processing, and Social Cognition. Each score is derived as follows: 0=not present in the past week; 1=present (during past week) and mild; 2=present (during past week) and moderate; 3=present (during past week) and severe; and 4=present (during past week) and extreme; and the item score is set to missing/unknown. The NY-AACENT total score is calculated by summing up 7 individual item scores at participant-visit level. The Total range is 0-28. Higher scores reflects greater severity and frequency of cognitive problems and lower scores shows absence or mild cognitive issues.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Number of Participants With Stages of Tanner Scale Score at Baseline and Month 24	The Tanner scale is a classification system used to assess physical development during puberty, detailing five distinct stages of growth. The Tanner Staging Scale assessment consists of 2 domains for girls and 3 domains for boys. Participants with change in Tanner Staging Scale (Stage 1-5) Score are reported.	Baseline, Month 24
Change From Baseline in the PANSS Total Score	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) to 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 ranges from 30 (best possible outcome) to 210 (worst possible outcome). Higher scores indicate worsening of symptoms. A negative change from baseline reflects improvement or reduction in symptom severity.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Change From Baseline in the PANSS Positive Subscale Scores	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) to 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive (+ve) scale items, 7 negative (-ve) scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranges from 30 (best possible outcome) to 210 (worst possible outcome). Higher scores indicate worsening of symptoms. A negative change from baseline reflects improvement or reduction in symptom severity.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Change From Baseline in the PANSS Negative Subscale Scores	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) to 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 ranges from 30 (best possible outcome) to 210 (worst possible outcome). Higher scores indicate worsening of symptoms. A negative (-ve) change from baseline reflects improvement or reduction in symptom severity.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Change From Baseline in Children's Global Assessment Scale (CGAS) Total Score	The CGAS is a 100-point rating scale measuring psychological, social and school functioning for children aged 6-17. The scale is separated into 10-point sections with the score ranging from 0-100, 1 to 10 indicates the need for constant supervision and 91 to 100 indicates superior functioning in all areas. A positive change from baseline reflects improvement in functioning.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Clinical Global Impression Severity (CGI-S) Scale Score	The CGI-S scale is an investigator-rated evaluation that assesses the severity of a participant's illness on a 7-point scale, ranging from 1 to 7. The investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" Response choices include: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients. Higher scores indicate worse condition.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)
Mean Clinical Global Impression - Improvement (CGI-I) Scale Score	The efficacy of brexpiprazole in the treatment was rated for each participant using the CGI-I. The investigator rated the participant's total improvement whether or not it was entirely due to drug treatment on a 7-point scale, ranging from 0 to 7. Response choices were: 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. Higher scores indicate worse condition.	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)

Other Outcome Measures

Outcome Measure	Time Frame
Time to Discontinuation Due to AEs	From the first dose of the study drug up to the last dose in the open-label treatment period (Up to Month 24)

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: H. Lundbeck A/S
• Investigators: Study Director: Heather Guthrie, MD, Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Atkinson SD, Shah A, Burgess MV, Hefting N, Chen D, Ward C. Safety and Tolerability of Brexpiprazole in Adolescents With Schizophrenia: A Long-Term, Open-Label Study. JAACAP Open. 2024 May 27;3(2):313-322. doi: 10.1016/j.jaacop.2024.04.005. eCollection 2025 Jun.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2017
• Primary Completion (Actual): April 22, 2025
• Study Completion (Actual): April 22, 2025

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 3, 2017

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Schizophrenia; Brexpiprazole
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Dopamine Agents; Dopamine Agonists; Serotonin Agents; brexpiprazole
• Other Study ID Numbers: 331-10-236

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No