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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
252
Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)
Aripiprazole (10-mg, 15-mg, 20-mg, 25-mg or 30-mg)
Study Site
Downy, California, United States
Study Site
Glendale, California, United States
Study Site
Miami, Florida, United States
Study Site
Miami Springs, Florida, United States
Study Site
Atlanta, Georgia, United States
Study Site
Overall Relapse Rate (in Percent) From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse.
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.
Time frame: Baseline to Week 52/End of Phase 3 visit.
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria.
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.
Time frame: Baseline to Week 52/End of Phase 3 visit.
Percentage of Responders in Each Treatment Group.
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.
Time frame: Baseline to Week 52/End of Phase 3 visit
Percentage of Participants Who Had Achieved Remission.
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.
Time frame: Baseline to Week 52/End of Phase 3 visit.
Percentage of Participants Who Discontinued Due to All Reasons Other Than Sponsor Discontinued Study.
Percentage of participants discontinued due to all reasons other than sponsor discontinued study were noted.
Time frame: Baseline to Week 52/End of Phase 3 visit
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Bloomfield Hills, Michigan, United States
Study Site
Chapel Hill, North Carolina, United States
Study Site
Bothell, Washington, United States
Study Site
Vijayawada, Andhra Pradesh, India
Study Site
Visakhapatnam, Andhra Pradesh, India
...and 42 more locations