Efficacy & Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia

Phase 3

Completed

Conditions: Schizophrenia

Interventions: Drug: Aripiprazole

Registration Number: NCT01149655

Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary: This will be a randomized, double-blind, placebo-controlled study consisting of a screening period, a conversion phase (Phase 1), a stabilization phase (Phase 2), and a double-blind maintenance treatment phase (Phase 3), and a follow up period.

Subjects may be either outpatients or inpatients between screening and through the time they reach stabilization at the end of Phase 2; hospitalization is not a study requirement. However, eligible subjects must be outpatients at the beginning of Phase 3.

Subjects will be assessed weekly during Phase 1, weekly for the first 4 weeks of Phase 2 and 3, and biweekly for the remaining weeks during each of Phases 2 and 3. Subjects will be encouraged to call the investigators with any exacerbation of psychotic symptoms and/or any tolerability issues. The investigator will also have the option to phone the subjects and their guardian(s) at any time to ensure clinical stability.

A data monitoring committee (DMC) will provide oversight for safety monitoring and reviewing the interim analysis. One interim analysis is planned after 75% of the total expected number of impending relapse events (28 events) are achieved and will be conducted by an independent data analysis center. The DMC will make a recommendation about stopping or continuing the study based on safety and efficacy reviews. The results of the interim analysis and individual subject data will remain blinded to the sponsor during the course of the study until the DMC determines that the study will conclude based on the results of the interim analysis, or the study is completed after 37 endpoint events.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 252

Inclusion Criteria

Subjects with a current DSM-IV-TR diagnosis of schizophrenia, and a history of the illness (diagnosis or symptoms) for at least 6 months prior to screening.
Subjects who have shown previous response to antipsychotic treatment (other than clozapine) and are not resistant to treatment with other antipsychotics.
Subjects who are currently being treated with oral or depot antipsychotics other than clozapine.
Subjects with a history of relapse and/or exacerbation of symptoms when they are not receiving antipsychotic treatment.

Exclusion Criteria

Subjects with a current DSM-IV-TR diagnosis other than schizophrenia.
Subjects 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 (i.e., medication, illicit drug use, etc.).
Subjects with attention deficit disorder or attention deficit hyperactivity disorder and/or subjects who were on a stimulant treatment for any period of time over the last one year prior to screening.
Subjects with any neurodevelopmental disorder, except Tourette's syndrome.
Subjects experiencing acute depressive symptoms within the past 30 days prior to screening.
Subjects who meet the DSM-IV-TR criteria for substance dependence (including alcohol and benzodiazepines, but excluding caffeine and nicotine) within the past 180 days prior to screening.
Subjects who have epilepsy, a history of seizures (except for a single childhood febrile seizure or post-traumatic seizure), or a history of severe head trauma or stroke, or have a history or current evidence of other unstable medical conditions.
Subjects with a history of subclinical hypothyroidism (TSH ≥ 4.0 mIU/L), known hypothyroidism or hyperthyroidism (unless the condition has been stabilized with medication for at least 90 days prior to entry into Phase 1 or Phase 2).
Subjects who have a medical history of uncontrolled diabetes, labile or unstable diabetes (brittle diabetes), newly diagnosed diabetes, or clinically significant abnormal blood glucose levels.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2	Aripiprazole	Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)
Phase 1	Aripiprazole	Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)
Phase 3	Aripiprazole	Aripiprazole (10-mg, 15-mg, 20-mg, 25-mg or 30-mg) or placebo

Primary Outcome Measures

Name	Time	Method
Overall Relapse Rate (in Percent) From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse.	Baseline to Week 52/End of Phase 3 visit.	The primary efficacy variable was overall relapse rate from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score \> 4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content). OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria.	Baseline to Week 52/End of Phase 3 visit.	Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score \> 4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items. OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.
Percentage of Responders in Each Treatment Group.	Baseline to Week 52/End of Phase 3 visit	Percentage of responders in each treatment group (i.e, response defined as meeting stability criteria). Participants stabilized on aripiprazole (trial drug) within the approved dose range of 10 to 30 mg/day and are tolerable based on clinical judgment.
Percentage of Participants Who Had Achieved Remission.	Baseline to Week 52/End of Phase 3 visit.	Percentage of participants who had achieved remission, where remission was defined as a score of ≤ 3 on each of the following specific PANSS items, maintained for a period of 6 months: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/ posturing, blunted affect, social withdrawal, and lack of spontaneity.
Percentage of Participants Who Discontinued Due to All Reasons Other Than Sponsor Discontinued Study.	Baseline to Week 52/End of Phase 3 visit	Percentage of participants discontinued due to all reasons other than sponsor discontinued study were noted.