Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia

Stable was defined as meeting all of the following criteria: Outpatient status; Positive and negative syndrome scale (PANSS) total score ≤ 80; Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): 1) conceptual disorganization 2) suspiciousness 3) hallucinatory behavior 4) unusual thought content; Clinical Global Impression of Severity (CGI-S) ≤ 4 (moderately ill); and Clinical Global Impression for Severity of Suicidality (CGI-SS) ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2. The percentage of stable participants at baseline who remain stable at endpoint (last visit) is described here.

Time frame: Baseline to Week 52/Last visit

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. N defines number of stable participants at baseline who were evaluated at the specified trial week.

To assess CGI-S, the rater or physician will answer the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time? Response choices include: 0 = not assessed; 1 = normal, not ill at all; 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, Weeks 12, 24, 52 and last visit

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed with baseline or at least one postbaseline assessment are included here.

PANSS positive subscale score (range 7-49) is the sum of the rating scores for the 7 positive scale items from the PANSS scale. Positive subscale consists of 7 positive symptom constructs: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). PANSS negative subscale score (range 7-49) is the sum of the rating scores for the 7 negative scale items from the PANSS scale. Negative subscale consists of 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive pathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking). The severity of each scale is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.

Time frame: Baseline, Weeks 12, 24, 52 and last visit

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed with baseline or at least one postbaseline assessment are included here.

PANSS total score (range 30-210) is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS scale. PANSS positive subscale score (range 7-49) is the sum of the rating scores for the 7 positive scale items from the PANSS scale. PANSS negative subscale score (range 7-49) is the sum of the rating scores for the 7 negative scale items from the PANSS scale. The severity of each scale is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.

Time frame: Baseline, Weeks 12, 24, 52 and last visit

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed with baseline or at least one postbaseline assessment are included here.

To assess CGI-I the rater or physician will rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses will be compared to the participants condition at baseline. Response choices include: 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: Weeks 2, 4, 12, 24, 52 and last visit

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed with baseline or at least one postbaseline assessment are included here.

Remission is defined as a score of ≤ 3 on each of the following specific PANSS items, maintained for a period of six months: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted affect, social withdrawal, and lack of spontaneity.

Time frame: Overall remission from Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48 and 52

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. N defines number of participants evaluated at the specified trial week.

Impending relapse criteria was defined as meeting all the following criteria: 1) Clinical Global Impression of Improvement (CGI-I) ≥ 5 (minimally worse), AND an increase to score of \>4 and absolute increase of ≥ 2 on the individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content); or an increase to score \>4 and absolute increase of ≥ 4 on the combined 4 PANSS items on any of these PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) OR 2) Hospitalization due to worsening of psychotic symptoms, but excluding hospitalization for psychosocial reasons, OR 3) CGI-SS score of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2, OR 4) Violent behavior resulting in clinically relevant self-injury, injury to another person, or property damage.

Time frame: Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48,52, and Last visit (upto 4 weeks ± 3 days after completion or withdrawal)

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. N defines number of participants evaluated at the specified trial week.

Stable was defined as meeting all of the following criteria: Outpatient status; PANSS total score ≤ 80; Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): 1) conceptual disorganization 2) suspiciousness 3) hallucinatory behavior 4) unusual thought content; Clinical Global Impression of Severity (CGI-S) ≤ 4 (moderately ill); and Clinical Global Impression for Severity of Suicidality (CGI-SS) ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2. The percentage of stable participants at baseline who remain stable at Week 28 is described here.

Time frame: Baseline to Week 28

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. N defines number of stable participants at baseline who were evaluated at the specified trial week.

Participants who discontinued due to any cause were noted. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.

Time frame: Baseline to Week 52

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included.

Participants who first time meet relapse criteria were considered as having an event at date of exacerbation of psychotic symptoms/impending relapse. Time to first event was calculated as the earliest date of meeting one of relapse criteria. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.

Time frame: Baseline to Week 52

Population: All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed had available assessments for evaluation of exacerbation of psychotic symptoms/impending relapse.