Trial Outcomes & Findings for Open-label, Extension Study of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in Patients With Schizophrenia (NCT NCT01683058)

NCT ID: NCT01683058

Last Updated: 2015-03-31

Results Overview

A TEAE was defined as an AE that began after the first injection or was continuous from Baseline and was serious, study drug-related, or resulted in death.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 74 participants
• Primary outcome timeframe: Baseline to Week 24
• Results posted on: 2015-03-31

Participant Flow

A multicenter, open-label, single-arm rollover trial designed to demonstrate the safety of aripiprazole intramuscular (IM) depot [400 or 300 milligrams (mg)] for the acute treatment of participants with schizophrenia, who met completion criteria in the registration trial NCT01663532. 74 participants were enrolled in this trial.

Participants entered this trial after completing the Week 12/Early Termination (ET) visit of trial NCT01663532 as it served as the Baseline evaluations for this trial.

Participant milestones

Measure	Aripiprazole IM Depot 400/300 mg All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Overall Study STARTED	74
Overall Study COMPLETED	45
Overall Study NOT COMPLETED	29

Reasons for withdrawal

Measure	Aripiprazole IM Depot 400/300 mg All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Overall Study Lost to Follow-up	9
Overall Study Adverse Event	6
Overall Study Subject Met Withdrawal Criteria	5
Overall Study Withdrawal by Subject	7
Overall Study Lack of Efficacy	2

Baseline Characteristics

Open-label, Extension Study of Aripiprazole Intramuscular Depot (OPC-14597, Lu AF41155) in Patients With Schizophrenia

Baseline characteristics by cohort

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Age, Continuous	43.0 Years STANDARD_DEVIATION 11.7 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: In safety analysis, all enrolled participants took at least one injection of aripiprazole IM depot 400/300mg in the IM depot treatment period.

A TEAE was defined as an AE that began after the first injection or was continuous from Baseline and was serious, study drug-related, or resulted in death.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Percentage of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Discontinued Investigational Medicinal Product (IMP) Due to AEs, Serious TEAEs and Outcome of Death Participants with TEAEs	66.2 Percentage of participants
Percentage of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Discontinued Investigational Medicinal Product (IMP) Due to AEs, Serious TEAEs and Outcome of Death Participants with serious TEAEs	6.8 Percentage of participants
Percentage of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Discontinued Investigational Medicinal Product (IMP) Due to AEs, Serious TEAEs and Outcome of Death Participants with severe TEAEs	8.1 Percentage of participants
Percentage of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Discontinued Investigational Medicinal Product (IMP) Due to AEs, Serious TEAEs and Outcome of Death Participants discontinued IMP due to AEs	8.1 Percentage of participants
Percentage of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Discontinued Investigational Medicinal Product (IMP) Due to AEs, Serious TEAEs and Outcome of Death Deaths	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: In safety analysis, all enrolled participants took at least one injection of aripiprazole IM depot 400/300mg in the IM depot treatment period.

Data collected from C-SSRS were mapped into C-CASA. The Columbia Classification Algorithm of Suicide Assessment (C-CASA) method and C-SSRS(text in parentheses as said below) were mapped as; 1= completed suicide(completed suicide); 2= suicide attempt(actual attempt); 3= preparatory actions toward imminent suicidal behavior (interrupted attempt, aborted attempt and preparatory acts/behavior); 4= suicidal ideation(wish to die,active suicidal thought, active suicidal thought with method, active suicidal thought with intent,active suicidal thought with plan/intent); 5= self-injurious behavior, intent unknown; 6= not enough information: death; 7= non-suicidal self-injurious behavior(nonsuicidal self-injurious behavior); 8= other accident; psychiatric/medical; 9= not enough information/non-death. C-CASA category 5, 6, 8 and 9 are not applicable. For each item, each participant received an intensity score from 0(none) to 5(worst). Suicidal ideation intensity total score range from 0 to 25.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS) Week 4 (N= 69)	-0.1 Units on a scale Standard Deviation 2.3
Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS) Week 8 (N= 61)	-0.1 Units on a scale Standard Deviation 2.2
Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS) Week 12 (N= 57)	-0.3 Units on a scale Standard Deviation 2.0
Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS) Week 16 (N= 52)	0.7 Units on a scale Standard Deviation 4.7
Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS) Week 20 (N= 44)	0.3 Units on a scale Standard Deviation 2.0
Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS) Week 24 (N= 45)	0.0 Units on a scale Standard Deviation 0.0
Mean Change From Baseline in Suicidal Ideation Intensity Total Score by the Columbia Suicide Severity Rating Scale (C-SSRS) Last Visit (N= 71)	0.6 Units on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: In safety analysis, all enrolled participants took at least one injection of aripiprazole IM depot 400/300mg in the IM depot treatment period.

The EPS rating scales included SAS total score (range 10-50) was the sum of the rating scores for 10 items from the SAS panel. This scale consists of a list of 10 symptoms, each to be rated on a 5-point scale of severity. For each symptom, the rating which best described the patient's condition were, 1= gait; 2= arm dropping; 3= shoulder shaking; 4= elbow rigidity; 5= wrist rigidity; 6= head rotation; 8= tremor; 9= salivation; 10= akathisia.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=72 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change From Baseline by Week by Extrapyramidal Symptoms (EPS) Evaluated Using the Simpson-Angus Scale (SAS) Week 12 (N= 66)	0.19 Units on a scale Standard Deviation 1.51
Mean Change From Baseline by Week by Extrapyramidal Symptoms (EPS) Evaluated Using the Simpson-Angus Scale (SAS) Week 24 (N= 70)	0.04 Units on a scale Standard Deviation 1.62

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: In safety analysis, all enrolled participants took at least one injection of aripiprazole IM depot 400/300mg in the IM depot treatment period.

EPS rating scale included the AIMS movement rating score (range 0-28) was the sum of the rating scores for facial and oral movements (i.e., item 1 - 4), extremity movements (i.e. item 5 - 6), and trunk movements (i.e. item 7). The symptoms for facial and oral movements were 1= muscles of facial expression, 2= lips and perioral area, 3= jaw and 4=tongue; extremity movements were, 5= upper (arms, wrists, hands, fingers), lower (legs, knees, ankles, toes), 7= neck, shoulders, hips). This scale consisted of 10 items, each to be rated on a 4-point scale of severity, and 2 questions to be answered by yes or no. To complete the scale, the patient was observed unobtrusively at rest (e.g., in waiting room). The chair used for this examination was hard, firm one without arms.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=73 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change From Baseline by Week by EPS Evaluated Using the Abnormal Involuntary Movement Scale (AIMS) Week 12 (N= 65)	-0.06 Units on a scale Standard Deviation 0.81
Mean Change From Baseline by Week by EPS Evaluated Using the Abnormal Involuntary Movement Scale (AIMS) Week 24 (N= 70)	0.07 Units on a scale Standard Deviation 1.28

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: In safety analysis, all enrolled participants took at least one injection of aripiprazole IM depot 400/300mg in the IM depot treatment period.

The BARS global score (range 0-5) was derived from the global clinical assessment of akathisia from the BARS panel were, 0= absent; 1= questionable; 2= mild akathisia; 3= moderate akathisia; 4= marked akathisia; 5= severe akathisia. Patients were observed while they were seated and then standing (for a minimum of 2 minutes in each position). Symptoms were observed in other situations (e.g., while engaged in neutral conversation, engaged in activity on the ward) was also rated.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=73 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change From Baseline by Week by EPS Evaluated Using Barnes Akathisia Rating Scale (BARS) Week 12 (N= 65)	0.19 Units on a scale Standard Deviation 0.73
Mean Change From Baseline by Week by EPS Evaluated Using Barnes Akathisia Rating Scale (BARS) Week 24 (N= 70)	0.14 Units on a scale Standard Deviation 0.91

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The body temperature, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure, and respiratory rate that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Body Temperature From Baseline in All Participants. Week 4 (N= 69)	0.1 °C Standard Deviation 0.4
Mean Change in Body Temperature From Baseline in All Participants. Week 8 (N= 61)	-0.0 °C Standard Deviation 0.4
Mean Change in Body Temperature From Baseline in All Participants. Week 12 (N= 58)	0.0 °C Standard Deviation 0.4
Mean Change in Body Temperature From Baseline in All Participants. Week 16 (N= 53)	0.0 °C Standard Deviation 0.3
Mean Change in Body Temperature From Baseline in All Participants. Week 20 (N= 44)	0.1 °C Standard Deviation 0.4
Mean Change in Body Temperature From Baseline in All Participants. Week 24 (N= 45)	0.1 °C Standard Deviation 0.4
Mean Change in Body Temperature From Baseline in All Participants. Last visit (N= 72)	0.0 °C Standard Deviation 0.4

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The heart rate supine, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure, and respiratory rate that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Heart Rate Supine From Baseline in All Participants. Week 12 (N= 58)	1.3 beats/min Standard Deviation 10.8
Mean Change in Heart Rate Supine From Baseline in All Participants. Week 16 (N= 53)	4.7 beats/min Standard Deviation 12.0
Mean Change in Heart Rate Supine From Baseline in All Participants. Week 20 (N= 44)	3.6 beats/min Standard Deviation 9.8
Mean Change in Heart Rate Supine From Baseline in All Participants. Week 24 (N= 45)	1.7 beats/min Standard Deviation 12.7
Mean Change in Heart Rate Supine From Baseline in All Participants. Last visit (N= 72)	3.4 beats/min Standard Deviation 12.1
Mean Change in Heart Rate Supine From Baseline in All Participants. Week 4 (N= 69)	3.8 beats/min Standard Deviation 10.9
Mean Change in Heart Rate Supine From Baseline in All Participants. Week 8 (N= 61)	2.3 beats/min Standard Deviation 11.2

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The systolic supine BP, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure, and respiratory rate that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants. Week 4 (N= 69)	1.9 mmHg Standard Deviation 12.8
Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants. Week 8 (N= 61)	1.3 mmHg Standard Deviation 12.2
Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants. Week 12 (N= 58)	-0.2 mmHg Standard Deviation 12.4
Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants. Week 16 (N= 53)	2.0 mmHg Standard Deviation 12.4
Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants. Week 20 (N= 44)	4.8 mmHg Standard Deviation 12.8
Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants. Week 24 (N= 45)	0.7 mmHg Standard Deviation 11.3
Mean Change in Systolic Supine Blood Pressure (BP) From Baseline in All Participants. Last visit (N= 72)	0.4 mmHg Standard Deviation 13.1

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The diastolic supine BP, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure and respiratory rate that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Diastolic Supine BP From Baseline in All Participants. Week 4 (N= 69)	0.1 mmHg Standard Deviation 8.6
Mean Change in Diastolic Supine BP From Baseline in All Participants. Week 8 (N= 61)	-1.3 mmHg Standard Deviation 8.1
Mean Change in Diastolic Supine BP From Baseline in All Participants. Week 12 (N= 58)	-0.9 mmHg Standard Deviation 7.7
Mean Change in Diastolic Supine BP From Baseline in All Participants. Week 16 (N= 53)	0.3 mmHg Standard Deviation 8.6
Mean Change in Diastolic Supine BP From Baseline in All Participants. Week 24 (N= 45)	0.4 mmHg Standard Deviation 9.7
Mean Change in Diastolic Supine BP From Baseline in All Participants. Last visit (N= 72)	0.5 mmHg Standard Deviation 9.9
Mean Change in Diastolic Supine BP From Baseline in All Participants. Week 20 (N= 44)	-0.0 mmHg Standard Deviation 9.6

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The heart rate sitting, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure and respiratory rate that were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant was supine for at least 5 minutes and again after the participant was sitting for approximately 2 minutes.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Heart Rate From Baseline in All Participants. Week 24 (N= 45)	0.6 beats/min Standard Deviation 13.6
Mean Change in Heart Rate From Baseline in All Participants. Week 8 (N= 61)	1.4 beats/min Standard Deviation 10.1
Mean Change in Heart Rate From Baseline in All Participants. Week 12 (N= 58)	-1.1 beats/min Standard Deviation 10.8
Mean Change in Heart Rate From Baseline in All Participants. Week 20 (N= 44)	3.3 beats/min Standard Deviation 10.1
Mean Change in Heart Rate From Baseline in All Participants. Week 16 (N= 53)	4.3 beats/min Standard Deviation 12.0
Mean Change in Heart Rate From Baseline in All Participants. Week 4 (N= 69)	1.2 beats/min Standard Deviation 9.1
Mean Change in Heart Rate From Baseline in All Participants. Last visit (N= 72)	1.9 beats/min Standard Deviation 13.0

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The systolic sitting BP, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure and respiratory rate that were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant was supine for at least 5 minutes and again after the participant was sitting for approximately 2 minutes.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Systolic BP From Baseline in All Participants. Week 20 (N= 44)	1.0 mmHg Standard Deviation 11.5
Mean Change in Systolic BP From Baseline in All Participants. Week 24 (N= 45)	-0.4 mmHg Standard Deviation 12.5
Mean Change in Systolic BP From Baseline in All Participants. Last visit (N= 72)	-0.7 mmHg Standard Deviation 13.4
Mean Change in Systolic BP From Baseline in All Participants. Week 4 (N= 69)	-0.1 mmHg Standard Deviation 13.0
Mean Change in Systolic BP From Baseline in All Participants. Week 8 (N= 61)	-0.3 mmHg Standard Deviation 11.3
Mean Change in Systolic BP From Baseline in All Participants. Week 12 (N= 58)	-0.7 mmHg Standard Deviation 11.3
Mean Change in Systolic BP From Baseline in All Participants. Week 16 (N= 53)	1.6 mmHg Standard Deviation 12.1

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The diastolic sitting BP, which is a vital sign parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of treatment-emergent adverse events of potential clinical relevance included abnormal values in body temperature, heart rate, systolic and diastolic blood pressure and respiratory rate that were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant was supine for at least 5 minutes and again after the participant was sitting for approximately 2 minutes.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Diastolic BP From Baseline in All Participants. Week 16 (N= 53)	0.8 mmHg Standard Deviation 7.8
Mean Change in Diastolic BP From Baseline in All Participants. Last visit (N= 72)	1.4 mmHg Standard Deviation 10.0
Mean Change in Diastolic BP From Baseline in All Participants. Week 4 (N= 69)	-0.9 mmHg Standard Deviation 9.7
Mean Change in Diastolic BP From Baseline in All Participants. Week 8 (N= 61)	-1.7 mmHg Standard Deviation 9.4
Mean Change in Diastolic BP From Baseline in All Participants. Week 12 (N= 58)	-0.2 mmHg Standard Deviation 7.9
Mean Change in Diastolic BP From Baseline in All Participants. Week 20 (N= 44)	-0.2 mmHg Standard Deviation 10.0
Mean Change in Diastolic BP From Baseline in All Participants. Week 24 (N= 45)	0.4 mmHg Standard Deviation 9.8

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The measurement ventricular rate is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Ventricular Rate From Baseline in All Participants. Week 12 (N= 56)	-1.5 Beats/min Standard Deviation 12.0
Mean Change in Ventricular Rate From Baseline in All Participants. Week 24 (N= 43)	-1.1 Beats/min Standard Deviation 12.3
Mean Change in Ventricular Rate From Baseline in All Participants. Last visit (N= 70)	-0.1 Beats/min Standard Deviation 13.7

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The measurement PR interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in PR Interval From Baseline in All Participants. Week 12 (N= 56)	3.5 msec Standard Deviation 11.1
Mean Change in PR Interval From Baseline in All Participants. Week 24 (N= 43)	0.5 msec Standard Deviation 12.5
Mean Change in PR Interval From Baseline in All Participants. Last visit (N= 70)	0.9 msec Standard Deviation 11.6

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The measurement RR interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in RR Interval From Baseline in All Participants. Week 24 (N= 43)	23.3 msec Standard Deviation 152.2
Mean Change in RR Interval From Baseline in All Participants. Last visit (N= 70)	8.0 msec Standard Deviation 158.4
Mean Change in RR Interval From Baseline in All Participants. Week 12 (N= 56)	23.7 msec Standard Deviation 140.9

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The measurement QRS interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in QRS Interval From Baseline in All Participants. Week 12 (N= 56)	-0.1 msec Standard Deviation 5.0
Mean Change in QRS Interval From Baseline in All Participants. Week 24 (N= 43)	0.4 msec Standard Deviation 5.3
Mean Change in QRS Interval From Baseline in All Participants. Last visit (N= 70)	0.0 msec Standard Deviation 5.7

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The measurement QT interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in QT Interval From Baseline in All Participants. Week 12 (N= 56)	3.1 msec Standard Deviation 21.5
Mean Change in QT Interval From Baseline in All Participants. Week 24 (N= 43)	1.5 msec Standard Deviation 24.9
Mean Change in QT Interval From Baseline in All Participants. Last visit (N= 70)	1.0 msec Standard Deviation 25.7

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The measurement QTcB interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in QTcB Interval From Baseline in All Participants. Week 12 (N= 56)	-1.6 msec Standard Deviation 20.2
Mean Change in QTcB Interval From Baseline in All Participants. Week 24 (N= 43)	-2.4 msec Standard Deviation 19.4
Mean Change in QTcB Interval From Baseline in All Participants. Last visit (N= 70)	0.3 msec Standard Deviation 19.0

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The measurement QTcF interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in QTcF Interval From Baseline in All Participants. Week 12 (N= 56)	-0.2 msec Standard Deviation 13.9
Mean Change in QTcF Interval From Baseline in All Participants. Week 24 (N= 43)	-1.3 msec Standard Deviation 14.0
Mean Change in QTcF Interval From Baseline in All Participants. Last visit (N= 70)	0.3 msec Standard Deviation 12.9

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

The measurement QTcN interval is an ECG parameter were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, RR, QRS, QT, QTcB, QTcN and QTcF that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in QTcN Interval From Baseline in All Participants. Week 12 (N= 56)	-0.5 msec Standard Deviation 14.7
Mean Change in QTcN Interval From Baseline in All Participants. Week 24 (N= 43)	-1.7 msec Standard Deviation 14.3
Mean Change in QTcN Interval From Baseline in All Participants. Last visit (N= 70)	0.3 msec Standard Deviation 13.4

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety Sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

Clinically relevant body weight changes was one of the primary parameters to measure the safety and tolerability of individual participants. Each participant's body mass index (BMI) kilogram per square meter (kg/m2) were calculated from the screening. Body weight, BMI, and waist circumference changes were evaluated by calculating mean change from Baseline and by tabulating the incidence of ≥7% weight gain or loss.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Clinically Relevant Body Weight Changes From Baseline in All Participants. Week 12 (N= 57)	-0.1 Kg Standard Deviation 4.5
Mean Change in Clinically Relevant Body Weight Changes From Baseline in All Participants. Week 24 (N= 44)	1.3 Kg Standard Deviation 6.0
Mean Change in Clinically Relevant Body Weight Changes From Baseline in All Participants. Last visit (N= 71)	0.5 Kg Standard Deviation 5.8

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety Sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit).

Clinically relevant body mass index was one of the primary parameters to measure the safety and tolerability of individual participants. Each participant's body mass index (BMI) kilogram per square meter (kg/m2) were calculated from the screening. Body weight, BMI, and waist circumference changes were evaluated by calculating mean change from Baseline and by tabulating the incidence of ≥7% weight gain or loss.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Clinically Relevant Body Mass Index From Baseline in All Participants. Week 12 (N= 57)	-0.0 Kg/m2 Standard Deviation 1.5
Mean Change in Clinically Relevant Body Mass Index From Baseline in All Participants. Week 24 (N= 44)	0.5 Kg/m2 Standard Deviation 2.0
Mean Change in Clinically Relevant Body Mass Index From Baseline in All Participants. Last visit (N= 71)	0.2 Kg/m2 Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline to last visit

Population: Safety Sample was analyzed. All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit). Only Week 24 and last visit data was included.

Clinically relevant waist circumference was one of the primary parameters to measure the safety and tolerability of individual participants. Each participant's body mass index (BMI) kilogram per square meter (kg/m2) were calculated from the screening. Body weight, BMI, and waist circumference changes were evaluated by calculating mean change from Baseline and by tabulating the incidence of ≥7% weight gain or loss.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Mean Change in Clinically Relevant Waist Circumference From Baseline in All Participants. Week 24 (N= 44)	1.6 cm Standard Deviation 6.6
Mean Change in Clinically Relevant Waist Circumference From Baseline in All Participants. Last visit (N= 64)	1.3 cm Standard Deviation 6.0

SECONDARY outcome

Timeframe: Baseline to last visit

Population: All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit). There were no clinically relevant findings with regard to laboratory values reported in this study.

The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Number of Participants With Clinically Relevant Laboratory Values.	0 participants

SECONDARY outcome

Timeframe: Baseline to last visit

Population: All enrolled participants who took at least one injection of study medication in the IM depot treatment period. Last visit was defined as the last assessment visit in the treatment phase (scheduled or unscheduled visit). None of the abnormalities or findings were noted during physical examination were considered clinically relevant.

The physical examination evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in the following body systems: head, ears, eyes, nose, and throat; thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae.

Outcome measures

Measure	Aripiprazole IM Depot 400/300 mg n=74 Participants All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Number of Participants With Clinically Relevant Physical Examination.	0 participants

Adverse Events

Aripiprazole IM Depot 400/300 mg

Serious events: 5 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aripiprazole IM Depot 400/300 mg n=74 participants at risk All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	1.4% 1/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Psychiatric disorders Depression	2.7% 2/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Psychiatric disorders Schizophrenia	2.7% 2/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Psychiatric disorders Suicidal ideation	1.4% 1/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.

Other adverse events

Measure	Aripiprazole IM Depot 400/300 mg n=74 participants at risk All participants in this trial received aripiprazole IM depot 400/300 mg every 4 weeks for over 24 weeks.
Investigations Weight decreased	8.1% 6/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Investigations Weight increased	29.7% 22/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Metabolism and nutrition disorders Hyperlipidaemia	5.4% 4/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Nervous system disorders Akathisia	12.2% 9/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Nervous system disorders Headache	8.1% 6/74 • AEs were recorded from the time the ICF was signed until follow-up for safety 14 (±2) days after the last trial visit. A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place