Efficacy & Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia

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.

Population: For the primary analysis, participants that belonged to the ITT (intent to treat) data set were included in the analysis. Participants who were lost to follow-up or who were still in the study at the end of Week 52 were considered as censored on their date of last efficacy evaluation. The ITT data set comprised participants randomized to period 3.

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.

Population: The ITT data set comprised of all participants who were randomized to period 3.

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

Population: The ITT data set comprised of all participants who were randomized to period 3.

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.

Population: The ITT data set comprised of participants who were randomized to the double-blind treatment. For evaluation of remission, 48 of 98 aripiprazole participants and 19 of 48 placebo participants met the 6 month threshold for remission analysis. Of those, 21 of 48 aripiprazole participants and 8 of 19 placebo participants met criteria for remission.

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

Population: The ITT data set comprised of all participants were randomized to period 3.

Baseline for the double-blind maintenance phase was defined as the last visit with available data in the stabilization phase, and the CGI-I scale was completed prior to or on the first dose date in the double-blind maintenance phase. Response choices included: 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.

Time frame: Baseline to Week 52/End of Phase 3 visit.

Population: The ITT data set comprised of participants randomized to period 3. LOCF method was used to impute missing data. Week 1 participants analyzed were 94 and 45 and Week 2 to Week 52 participants analyzed were 97 and 48.

The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-s, the Investigator answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices included: 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 participants.

Time frame: Baseline to Week 52/End of Phase 3 visit.

Population: The ITT data set comprised of participants randomized to period 3. LOCF method was used to impute missing data. Week 1 participants analyzed were 94 and 45 and Week 2 to Week 52 participants analyzed were 97 and 48.

The CGAS was developed by Schaffer and colleagues to provide a global measure of severity of disturbance in children and adolescents. The CGAS is a rating scale for evaluating the overall functioning of a participant during a specified time period on a continuum from psychological or psychiatric sickness to health. The CGAS is a valid and reliable tool for rating a child's general level of functioning on a health-illness continuum. CGAS score (range 1-100) was a single item score for rating a child's general level of functioning on a health-illness continuum, with higher scores represented better functioning.

Time frame: Baseline to Week 52/End of Phase 3 visit.

Population: The ITT data set comprised of participants randomized to period 3. LOCF method was used to impute missing data. Week 1 participants analyzed were 95 and 45.

The PANSS consisted of 3 subscales were a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated (absence of symptoms) and a score of 7 indicated (extremely severe symptoms). The 7 negative symptom constructs were blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

Time frame: Baseline to Week 52/End of Phase 3 visit.

Population: The ITT data set comprised of participants randomized to period 3. LOCF method was used to impute missing data. Week 1 participants analyzed were 94 and 45.

The PANSS consisted of 3 subscales were a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated (absence of symptoms) and a score of 7 indicated (extremely severe symptoms). The 7 positive symptom constructs were delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

Time frame: Baseline to Week 52/End of Phase 3 visit.

Population: The ITT data set comprised of participants randomized to period 3. LOCF method was used to impute missing data. Week 1 participants analyzed were 94 and 45.

The PANSS consisted of 3 subscales with a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicates (absence of symptoms) and a score of 7 indicates (extremely severe symptoms). The symptom constructs for each subscale were positive subscale, negative subscale and general psychopathology subscale. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

Time frame: Baseline to Week 52/End of Phase 3 visit.

Population: The ITT data set comprised of participants randomized to period 3. LOCF (last observation carried forward) method was used to impute missing data. Week 1 had only 95 and 45 participants analyzed.