Trial Outcomes & Findings for Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia (NCT NCT00731549)

Last Updated: 2014-11-26

Results Overview

"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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1081 participants

Primary outcome timeframe

Baseline to Week 52/Last visit

Results posted on

2014-11-26

Participant Flow

This open label Phase 3 study enrolled participants from the maintenance phase of study NCT00705783 (31-07-246) and study NCT00706654 (31-07-247) and new participants. Participants received aripiprazole intramuscular (IM) depot as maintenance treatment.

Study comprised of screening phase (applicable if enrolled late/new participants/received antipsychotic treatment other than aripiprazole), conversion phase (Phase 1, to convert from other antipsychotics to aripiprazole), oral stabilization phase (Phase 2-aripiprazole 10-30 mg), and open-label IM phase (Phase 3-aripiprazole 400 mg IM depot).

Participant milestones

Participant milestones
Measure	Aripiprazole 400/300 mg IM Depot Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Overall Study STARTED	1081
Overall Study COMPLETED	858
Overall Study NOT COMPLETED	223

Reasons for withdrawal

Reasons for withdrawal
Measure	Aripiprazole 400/300 mg IM Depot Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Overall Study Lost to Follow-up	19
Overall Study Met withdrawal criteria	24
Overall Study Physician Decision	16
Overall Study Withdrawal by Subject	89
Overall Study Protocol deviation	1
Overall Study Adverse Event	31
Overall Study Lack of efficacy with AE	37
Overall Study Lack of efficacy without AE	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Age, Continuous	41.2 Years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	439 Participants n=5 Participants
Sex: Female, Male Male	642 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Baseline (N=1075)	100 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 2 (N=1023)	99.02 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 4 (N=1045)	99.14 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 8 (N=1009)	98.51 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 12 (N=988)	97.47 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 16 (N=951)	98.42 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 20 (N=919)	98.15 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 24 (N=880)	99.20 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 28 (N=854)	98.95 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 32 (N=838)	99.16 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 36 (N=814)	99.26 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 40 (N=807)	99.50 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 44 (N=784)	99.11 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 48 (N=751)	99.20 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Week 52 (N=671)	98.96 Percentage of participants
Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). Last visit (N=1072)	94.96 Percentage of participants

SECONDARY outcome

Timeframe: 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.

"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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Last visit (N=1079)	4.17 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 2 (N=1028)	0.49 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 4 (N=1049)	0.48 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 8 (N=1011)	0.79 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 12 (N=988)	1.52 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 16 (N=948)	0.84 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 20 (N=920)	1.09 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 24 (N=883)	0.45 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 28 (N=857)	0.58 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 32 (N=838)	0.36 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 36 (N=814)	0.25 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 40 (N=808)	0.25 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 44 (N=783)	0.26 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 48 (N=750)	0.27 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Week 52 (N=668)	0.30 Percentage of participants
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. Overall (N=1079)	8.25 Percentage of participants

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Percentage of Participants Achieving Remission.	51.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 28

"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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Percentage of Participants Stable at Baseline and Remaining Stable at Week 28. Baseline (N=1075)	100 Percentage of participants
Percentage of Participants Stable at Baseline and Remaining Stable at Week 28. Week 28 (N=854)	98.95 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1079 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Percentage of Participants With Time to First Exacerbation of Psychotic Symptoms/Impending Relapse.	8.2 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Mean Change From Baseline to Endpoint (Last Visit) in Positive and Negative Syndrome Scale (PANSS) Total Score. Last visit (N=1078)	-1.72 Units on a scale Standard Deviation 10.21
Mean Change From Baseline to Endpoint (Last Visit) in Positive and Negative Syndrome Scale (PANSS) Total Score. Week 12 (N=987)	-1.69 Units on a scale Standard Deviation 6.21
Mean Change From Baseline to Endpoint (Last Visit) in Positive and Negative Syndrome Scale (PANSS) Total Score. Week 24 (N=882)	-2.55 Units on a scale Standard Deviation 7.08
Mean Change From Baseline to Endpoint (Last Visit) in Positive and Negative Syndrome Scale (PANSS) Total Score. Week 52 (N=669)	-3.55 Units on a scale Standard Deviation 7.75

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 52 and last visit

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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score. Week 12 (N=987)	-0.11 Units on a scale Standard Deviation 0.52
Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score. Week 24 (N=883)	-0.17 Units on a scale Standard Deviation 0.53
Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score. Week 52 (N=668)	-0.24 Units on a scale Standard Deviation 0.56
Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score. Last visit (N=1079)	-0.14 Units on a scale Standard Deviation 0.70

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 52 and last visit

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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. Week 24 negative subscale score (N=882)	-0.53 Units on a scale Standard Deviation 2.52
Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. Week 12 positive subscale score (N=987)	-0.42 Units on a scale Standard Deviation 2.11
Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. Week 24 positive subscale score (N=882)	-0.68 Units on a scale Standard Deviation 2.26
Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. Week 52 positive subscale score (N=669)	-1.04 Units on a scale Standard Deviation 2.53
Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. Last visit positive subscale score (N=1078)	-0.49 Units on a scale Standard Deviation 3.38
Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. Week 12 negative subscale score (N=987)	-0.40 Units on a scale Standard Deviation 2.40
Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. Week 52 negative subscale score (N=669)	-0.80 Units on a scale Standard Deviation 2.94
Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. Last visit negative subscale score (N=1078)	-0.46 Units on a scale Standard Deviation 3.19

SECONDARY outcome

Timeframe: Weeks 2, 4, 12, 24, 52 and last visit

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.

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Mean Clinical Global Impression of Improvement (CGI-I) Score. Baseline (N=1081)	3.48 Units on a scale Standard Deviation 0.82
Mean Clinical Global Impression of Improvement (CGI-I) Score. Week 2 (N=1026)	3.52 Units on a scale Standard Deviation 0.85
Mean Clinical Global Impression of Improvement (CGI-I) Score. Week 4 (N=1049)	3.49 Units on a scale Standard Deviation 0.86
Mean Clinical Global Impression of Improvement (CGI-I) Score. Week 12 (N=987)	3.42 Units on a scale Standard Deviation 0.92
Mean Clinical Global Impression of Improvement (CGI-I) Score. Week 24 (N=882)	3.33 Units on a scale Standard Deviation 0.98
Mean Clinical Global Impression of Improvement (CGI-I) Score. Week 52 (N=669)	3.25 Units on a scale Standard Deviation 0.99
Mean Clinical Global Impression of Improvement (CGI-I) Score. Last visit (N=1079)	3.35 Units on a scale Standard Deviation 1.10

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Aripiprazole 400/300 mg IM Depot n=1081 Participants Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Percentage of Participants Who Discontinued Due to All Causes.	20.6 Percentage of participants

Adverse Events

Aripiprazole 400/300 mg IM Depot

Serious events: 95 serious events

Other events: 254 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Aripiprazole 400/300 mg IM Depot n=1081 participants at risk Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Blood and lymphatic system disorders Anaemia	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Cardiac disorders Atrial fibrillation	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Cardiac disorders Cardiac arrest	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Cardiac disorders Cardiac failure	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Cardiac disorders Cardiac failure acute	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Cardiac disorders Cardio-respiratory arrest	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Cardiac disorders Myocardial infarction	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Eye disorders Open angle glaucoma	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Eye disorders Uveitis	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Gastrointestinal disorders Dyspepsia	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Gastrointestinal disorders Pancreatitis acute	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Gastrointestinal disorders Stomach mass	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
General disorders Facial pain	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
General disorders Sudden death	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Hepatobiliary disorders Bile duct stone	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Hepatobiliary disorders Cholelithiasis	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Bronchitis	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Cellulitis	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Gangrene	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Genital candidiasis	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Hepatitis viral	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Influenza	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Pilonidal cyst	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Pneumonia	0.37% 4/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Respiratory tract infection	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Infections and infestations Syphilis	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Injury, poisoning and procedural complications Alcohol poisoning	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Injury, poisoning and procedural complications Concussion	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Injury, poisoning and procedural complications Hand fracture	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Injury, poisoning and procedural complications Intentional overdose	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Injury, poisoning and procedural complications Multiple injuries	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Investigations Liver function test abnormal	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Metabolism and nutrition disorders Dehydration	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Metabolism and nutrition disorders Hypoglycaemia	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Metabolism and nutrition disorders Hypovolaemia	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer metastatic	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer metastatic	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Nervous system disorders Convulsion	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Nervous system disorders Loss of consciousness	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Nervous system disorders Ruptured cerebral aneurysm	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Nervous system disorders Tremor	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Adjustment disorder	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Anxiety	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Depression	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Hallucination	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Hallucination, auditory	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Homicidal ideation	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Psychotic disorder	1.4% 15/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Schizoaffective disorder	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Schizophrenia	1.9% 21/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Schizophrenia, paranoid type	0.46% 5/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Suicidal ideation	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Suicide attempt	0.28% 3/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Reproductive system and breast disorders Menorrhagia	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Reproductive system and breast disorders Ovarian cyst	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Respiratory, thoracic and mediastinal disorders Asthma	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.19% 2/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Vascular disorders Arteriosclerosis	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Vascular disorders Hypertension	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Vascular disorders Hypotension	0.09% 1/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.

Other adverse events

Other adverse events
Measure	Aripiprazole 400/300 mg IM Depot n=1081 participants at risk Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Infections and infestations Nasopharyngitis	7.0% 76/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Nervous system disorders Headache	7.6% 82/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Anxiety	6.8% 73/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Psychiatric disorders Insomnia	6.6% 71/1081 • Phase 3 Week 1 to Week 52/Early termination. All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.

Additional Information

Global Medical Affairs

Otsuka Pharmaceutical Development & Commercialization, Inc

Phone: 800 562-3974

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place