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

• ClinicalTrials.gov Identifier: NCT03238326
• Recruitment Status: Active, not recruiting
• First Posted: August 3, 2017
• Last Update Posted: April 18, 2023
• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborator: H. Lundbeck A/S
• Information provided by (Responsible Party): Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Brexpiprazole	Phase 3

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 296 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: 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
• Actual Study Start Date: August 23, 2017
• Estimated Primary Completion Date: May 2025
• Estimated Study Completion Date: May 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Rollover & De-Novo; 1-4 mg/day; 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 Name: OPC-34712

Outcome Measures

Primary Outcome Measures :

1. Frequency & Severity of Adverse Events (AE) [Safety] [ Time Frame: Up to 24 months or early termination with a 21 day follow-up period ]
   Frequency and severity will be monitored; along with serious AEs & discontinuation from trial due to AE

Secondary Outcome Measures :

1. Mean change from baseline and incidence of clinically significant abnormalities in clinical laboratory tests [Safety] [ Time Frame: Up to 24 months or early termination ]
   Abnormalities in hematology, serum chemistry [including fasting blood lipids, glucose and insulin, serum prolactin], glycosylated hemoglobin [HbA1c], creatine phosphokinase [CPK] and urinalysis) results
2. Mean change from baseline and incidence of clinically significant abnormalities in vital signs [Safety] [ Time Frame: Up to 24 months or early termination with a 21 day follow-up period ]
   Mean change from baseline in supine and standing positions will be assessed and incidence of clinically significant abnormalities
3. Weight [Safety] [ Time Frame: Up to 24 months or early termination ]
   Change in weight, in kilograms, will be assessed for any notable differences from baseline
4. Height [Safety] [ Time Frame: Up to 24 months or early termination ]
   Change in height, in centimeters, will be assessed for any notable differences from baseline
5. Body Mass Index (BMI) [Safety] [ Time Frame: Up to 24 months or early termination ]
   Measured in kilograms/meter^2 and assessed to determine any notable differences from baseline
6. Waist Circumference [Safety] [ Time Frame: Up to 24 months or early termination ]
   Change in waist circumference, in centimeters will be assessed for any notable differences from baseline
7. Changes in ECG [Safety] [ Time Frame: Up to 24 months or early termination ]
   Mean change from baseline will be assessed and incidence of clinically significant abnormalities
8. Change in Abnormal Involuntary Movement Scale (AIMS) Score [Safety] [ Time Frame: Up to 24 months or early termination ]
   Mean change from baseline will be assessed
9. Change in Simpson-Angus Scale (SAS) Score [Safety] [ Time Frame: Up to 24 months or early termination ]
   Mean change from baseline will be assessed
10. Change in Barnes Akathisia Rating Scale (BARS) Score [Safety] [ Time Frame: Up to 24 months or early termination ]
    Mean change from baseline will be assessed
11. Potential suicide events recorded on the Columbia-Suicide Severity Rating Scale (C-SSRS) [Safety] [ Time Frame: Up to 24 months or early termination ]
    Analysis of potential suicide events recorded with C SSRS
12. Comprehensive psychotropic side effects as assessed by Udvalg for Kliniske Undersogelser (UKU) [Safety] [ Time Frame: Up to 24 months or early termination ]
    Psychotropic side effects will be assessed by UKU
13. The frequency of symptom items from New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) [Safety] [ Time Frame: Up to 24 months or early termination ]
    Frequency of symptom items will be assessed
14. Change in Tanner Staging Scale Scores [Safety] [ Time Frame: Up to 24 months or early termination ]
    Baseline and post-baseline data will be assessed
15. Time to discontinuation due to AE [ Time Frame: Up to 24 months or early termination ]
    Time to discontinue will be assessed as applicable
16. Change in the Positive and Negative Syndrome Scale (PANSS) Total Score and PANSS Subscale Scores [ Time Frame: Up to 24 months or early termination ]
    Change from baseline in total score will be assessed for efficacy of drug. Positive/Negative subscale scores will be assessed for efficacy of drug.
17. Change in Children's Global Assessment Scale (CGAS) Score [ Time Frame: Up to 24 months or early termination ]
    Change from baseline in CGAS will be assessed for efficacy of drug
18. Change in Clinical Global Impression Severity (CGI-S) Score [ Time Frame: Up to 24 months or early termination ]
19. Change in Clinical Global Impression Improvement (CGI-I) Score [ Time Frame: Up to 24 months or early termination ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Oklahoma

For additional information regarding sites, contact 844-687-8522

Oklahoma City, Oklahoma, United States, 73116

Sponsors and Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

H. Lundbeck A/S

Investigators

• Study Director: Caroline Ward, PhD.; Otsuka Pharmaceutical Development & Commercialization, Inc.

More Information

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT03238326
• Other Study ID Numbers: 331-10-236
• First Posted: August 3, 2017
• Last Update Posted: April 18, 2023
• Last Verified: April 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Brexpiprazole; Schizophrenia

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Brexpiprazole; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Dopamine Agonists; Dopamine Agents