Schizophrenia in Adolescent Patients or Child and Adolescent Patients with Bipolar I Disorder, Manic or Mixed Episode with or without Psychotic Features MedDRA version: 14.1 Level: PT Classification code 10039626 Term: Schizophrenia System Organ Class: 10037175 - Psychiatric disorders MedDRA version: 14.1 Level: PT Classification code 10004939 Term: Bipolar I disorder System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Trade Name: Abilify
Product Name: aripiprazole 2 mg tablet
Product Code: OPC-14597
Pharmaceutical Form: Tablet
INN or Proposed INN: Aripiprazole
CAS Number: 129722-12-9
Current Sponsor code: OPC-14597
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Assessed at Screening 1. Study specific written informed consent/assent obtained from a parent/guardian or legally acceptable representative, as applicable for local laws, prior to the initiation of any protocol-required procedures. In addition, the subject must provide informed assent at screening and must be able to understand that he or she can withdraw from the study at any time. All informed consent/assent procedures must be in accordance with the study center’s institutional review board/ethics committee (IRB/IEC) and local regulatory requirements. If the rollover subject should turn 18 years of age (or the age of adulthood as specified by local laws or regulations) within 4 weeks prior to entry into Study 267 or during Study 267 participation, an informed consent must be obtained from the subject. 2) Adolescent male and female subjects including: Schizophrenia: • De novo subjects aged 13 to 17 years at the time of signing the informed consent/assent • Rollover subjects from Study 266 Bipolar Manic or Mixed Episode: • De novo subjects aged 10 to 17 years at the time of signing the informed consent/assent. 3. All Subjects: Co-morbid diagnoses are permitted including Attention Deficit Disorder (ADD), Attention Deficit Hyperactivity Disorder (ADHD), Conduct Disorder (CD), and Oppositional Defiant Disorder (ODD) and anxiety disorders (except Post Traumatic Stress Disorder [PTSD] and Obsessive Compulsive Disorder [OCD]). Subjects with Schizophrenia: Subjects with a current diagnosis of schizophrenia, as defined by DSM-IV-TR criteria (and confirmed by the K-SADS-PL for de novo subjects only), and a history of the illness (diagnosis or symptoms) for at least 6 months prior to screening (as per subject, family, or healthcare provider, or by previous medical records). Schizophrenia must be the primary DSM-IV-TR axis I diagnosis. The diagnosis of schizophrenia must be made and documented initially by an adequately trained clinician (eg, adolescent psychiatrist or local medical equivalent). For de novo subjects, the diagnosis should be confirmed by utilizing the K-SADSPL performed by an adequately trained clinician once at the time of the entry into Study 267. If a rollover subject does not have a completed K-SADS-PL assessment from Study 266, then this assessment must be completed at Screening for Study 267. Subjects with Bipolar Manic or Mixed Episode: Subjects with a current diagnosis of Bipolar I disorder, manic or mixed episode with or without psychotic features experiencing symptoms at least for a week, as defined by Axis I (DSM-IV-TR) criteria, confirmed by K-SADS-PL, and have a Young Mania Rating Scale (YMRS) score = 20 at Baseline. 4. Subjects who, in the investigator’s judgment, require treatment with antipsychotic medication(s). 5. Subjects who have shown previous response to antipsychotic treatment (other than clozapine) and are not resistant to treatment with other antipsychotics, according to the investigator’s clinical judgment. 6. Subjects who are currently being treated with oral antipsychotics other than clozapine, and subjects who are not resistant to treatment with other antipsychotics. De novo subjects who have been without antipsychotic treatment for no more than 3 weeks prior to screening will be considered as being treated currently for the purpose of determining eligibility for this trial. 7. Inpatient or outpatient status, with the exception of acute hospitaliza
Exclusion criteria
Exclusion criteria: ALL SUBJECTS: 1) Sexually active males who are not practicing doublebarrier birth control or who will not remain abstinent during the study and for 90 days following the last dose of study medication, or sexually active females of childbearing potential who are not practicing doublebarrier birth control or who will not remain abstinent during the study and for 30 days following the last dose of study medication. Abstinence will be permitted if it is confirmed and documented at every study visit. If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device (IUD), birth control pill, birth control depot injections, implant, condom or sponge with spermicide. 2) Females who are breast-feeding and/or who have a positive serum pregnancy test result prior to receiving study drug. Target Disease 3) All Subjects: Axis I (DSM-IV-TR) diagnosis for schizoaffective disorder, autism, pervasive developmental disorder (PDD), OCD, or PTSD. Subjects with Schizophrenia: Subjects with a current major depressive episode. Subjects with Bipolar Manic or Mixed Episode: Subjects presenting with a clinical picture and/or history that is consistent with an Axis I (DSM-IV-TR) diagnosis of Bipolar II Disorder or Bipolar Disorder not otherwise specified (NOS). 4. Subjects with a clinical presentation and/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 (ie, medication, illicit drug use, etc.). 5. Any neurological disorder, with the exception of Tourette’s syndrome. 6. Subjects experiencing symptoms consistent with a major depressive episode at the time of screening other than subjects diagnosed with Bipolar I Disorder Mixed Episode. 7. Subjects with schizophrenia or Bipolar Manic or Mixed Episode that is considered treatment resistant to antipsychotic medication, including relapse while on adequate doses of aripiprazole, by history. 8. Subjects who are currently receiving clozapine or have received clozapine, regardless of dose or duration, at any time in the past are ineligible for entry into the study. 9. Subjects who have a significant risk of committing suicide based on history (eg, suicide attempt in the past 1 year) or routine psychiatric status examination, or who have an answer of “yes” on Questions 4 or 5 (current or over the last 30 days) on the suicidal ideation section of the baseline screening version of the C-SSRS. 10. Subjects who have met DSM-IV-TR criteria for substance dependence within the past 180 days prior to screening. 11. Subjects who have epilepsy, a history of seizures, or a history of severe head trauma or stroke, or have a history or current evidence of other unstable medical conditions that would expose them to undue risk of a significant AE or interfere with assessments of safety or efficacy during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, hematologic, or immunologic disease as determined by the clinical judgment of the investigator; subjects with a comorbid serious systemic illness that requires pharmacotherapy. 12. Subject with a history of subclinical hypothyroidism (TSH =4 mIU/L), known hypothyroidism or hyperthyroidism (unless condition has been stabilized wit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Throughout the duration of the study (max 12 months for rollover subjects) Throughout the duration of the study (max 24 months for Denovo subjects);Main Objective: The objective of this study is to further characterize the long-term safety and tolerability of aripiprazole in adolescent subjects with schizophrenia and child and adolescent subjects with Bipolar I Disorder, manic or mixed episode, with or without psychotic features.;Secondary Objective: Not applicable;Primary end point(s): Primary Endpoint: • The frequency and severity of AEs, SAEs (clinical and laboratory), and discontinuation from study due to AEs | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Throughout the duration of the study (max 12 months for rollover subjects) Throughout the duration of the study (max 24 months for Denovo subjects);Secondary end point(s): Safety: • Mean change from baseline and incidence of clinically significant abnormalities in clinical laboratory tests and urinalysis results (including fasting blood lipids, glucose and insulin, serum prolactin, HbA1c and creatinine phosphokinase [CPK]), vital signs (supine and standing positions) and ECG parameters. A central ECG service will be utilized to review all ECGs in order to standardize interpretations for the safety analysis. • Review of physical examination findings • Mean change from baseline of z-scores for height and body weight, mean changes of BMI and waist circumference • Mean change from baseline on the AIMS, SAS, and BARS • The frequency of symptom items for the clinician-administered New York Assessment for Adverse Cognitive Effects of Neuropsychiatric Treatment: (NY-AACENT). • Baseline and postbaseline Tanner Staging • Analysis of potential suicide events recorded on the C-SSRS • Time to discontinuation due to AE Efficacy: Schizophrenia: • Mean change from baseline in PANSS Total Score • Mean change from baseline in PANSS Positive and Negative subscales • Mean change from baseline in CGI-S score • Mean CGI-I score at endpoint • Mean change from baseline in CGAS Bipolar Manic or Mixed Episode: • Mean change from baseline in YMRS • Mean change from baseline in CGI-BP Severity • Mean CGI-BP Improvement score at endpoint • Mean change from baseline in GBI • Mean change from baseline in ADHD-RS-IV • Mean change from baseline in CGAS Other Outcomes: • Change from baseline for P-QLES-Q • Mean change from baseline on the PANSS Cognitive Subscale Score • Time to discontinuation for all reasons | — |
Countries
Bulgaria, Croatia, Hungary, India, Malaysia, Philippines, Poland, Romania, Russian Federation, Serbia, Taiwan, Ukraine, United States
Outcome results
None listed