Safety and Tolerability Trial of Aripiprazole IM Depot Treatment in Adult Subjects With Schizophrenia Stabilized on Oral Antipsychotics Other Than Aripiprazole

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01552772
• Collaborator: (none)
• Enrollment: 60
• Locations: 12
• Arm: 1
• Duration (Months): 3
• Patients Per Site: 5
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This study will test the safety of an aripiprazole injection in subjects with schizophrenia that are currently taking oral antipsychotic medication other than aripiprazole. Subjects in this study will receive one injection of aripiprazole and will need to stop taking their other antipsychotic medication two weeks after the injection. The study will last one month. Subjects will be required to come to a clinic for evaluations and drug and urine collection five times during the course of the study.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Aripiprazole IM Depot	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Safety and Tolerability Trial of Aripiprazole IM Depot Treatment Initiation in Adult Subjects With Schizophrenia Stabilized on Atypical Oral Antipsychotics Other Than Aripiprazole
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole IM Depot	Drug: Aripiprazole IM Depot; 400 mg intramuscular injection of aripiprazole; Other Names: Abilify

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AE). [From the time the informed consent (ICF) was signed until follow-up at 30 days after the last trial visit (Day 28).]

   An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the study physician. A serious adverse event (SAE) was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. TEAE stands for treatment emergent adverse events.

Secondary Outcome Measures

1. Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Observed Cases (OC) Data. [Baseline, Week 1, 2, 4 and Last visit (Day 28).]

   The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

2. Change From Baseline in Total Score of PANSS for Last Observation Carried Forward (LOCF) Data. [Baseline, Week 1, 2 and 4]

   The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

3. Change From Baseline in PANSS Positive Sub-scale Score for OC Data. [Baseline, Week 1, 2, 4 and Last visit (Day 28).]

   The Positive and Negative Syndrome Scale (PANSS) consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

4. Change From Baseline in PANSS Positive Sub-scale Score for LOCF Data. [Baseline, Week 1, 2 and 4]

   The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

5. Change From Baseline in PANSS Negative Sub-scale Score for OC Data. [Baseline, Week 1, 2, 4 and Last visit (Day 28).]

   The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

6. Change From Baseline in PANSS Negative Sub-scale Score for LOCF Data. [Baseline, Week 1, 2 and 4]

   The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

7. Change From Baseline in Clinical Global Impression Severity (CGI-S) Score in OC Data. [Baseline, Week 1, 2, 4 and Last visit (Day 28).]

   The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not 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.

8. Change From Baseline in CGI-S Score in LOCF Data. [Baseline, Week 1, 2 and 4.]

   The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not 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.

9. Clinical Global Impression Improvement (CGI-I) Scale Score in OC Data. [Week 1, 2, 4 and Last visit (Day 28).]

   The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition a 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.

10. CGI-I Scale Score in LOCF Data. [Week 1, 2 and 4]

    The efficacy of trial medication were rated for each participant using the Clinical Global Impression Improvement (CGI-I) scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition a 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male and female individuals between 18 and 64 years of age, inclusive, with a diagnosis of schizophrenia as defined by DSM-IV-TR criteria.

2. Good physical health as determined by no clinically significant deviation from normal in medical history, clinical laboratory determination, ECGs, or physical examinations.

3. Ability to provide written informed consent or consent obtained from a legally acceptable representative (as required by IRB) prior to the initiation of any protocol-required procedures.

4. Body mass index of 18 to 35 kg/m2, inclusive.

5. Prior history of tolerating aripiprazole.

6. Subjects must be treated with one of the following atypical oral antipsychotic medications: risperidone, olanzapine, quetiapine, ziprasidone, or paliperidone and be clinically stable, per the investigator's judgment, for 14 days prior to the administration of aripiprazole IM depot

Exclusion Criteria:

1. Sexually active males who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 180 days following the last dose of trial medication, or have not had an orchidectomy or sexually active females of childbearing potential who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 150 days following the last dose of trial medication. Abstinence will be permitted if it is confirmed and documented at every trial visit. If employing birth control, 2 of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control depot injections, implant, condom or sponge with spermicide. Note: Women of childbearing potential (WOCBP) are defined as all women unless they have had an oophorectomy or hysterectomy or have been postmenopausal for 12 consecutive months.

2. Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days; including alcohol and benzodiazepines, but excluding caffeine and nicotine. Subjects with a positive drug screen for cocaine or other drugs of abuse (excluding stimulants and other prescribed medications and marijuana).a

3. Subjects likely to require prohibited concomitant therapy during the trial, and use of any CYP2D6 and CYP3A4 inhibitors, or CYP3A4 inducers within 14 days prior to dosing and for the duration of the trial.

4. Females who are pregnant or lactating.

5. Subjects who had participated in any clinical trial involving a psychotropic medication within 1 month prior to enrollment; subjects who had participated in a previous IM depot trial within the last 6 months; or who had previously enrolled and received trial medication in an aripiprazole IM depot clinical trial.

6. Any major surgery within 30 days prior to enrollment.

7. Evidence of organ dysfunction or any clinically significant deviation from normal in physical, electrocardiographic, or clinical laboratory examinations.

8. Subjects who have a significant risk of committing suicide based on history or routine psychiatric status examination

9. Subjects currently in an acute relapse of schizophrenia.

10. Subjects with a current DSM-IV-TR diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.

11. Subjects who were considered treatment-resistant to antipsychotic medication. (Subjects needed to have shown a previous response to an antipsychotic medication other than clozapine.)

12. Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia.

13. Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	South Coast Clinical Trials	Anaheim	California	United States	92804
2	Comprehensive Clinical Development	Cerritos	California	United States	90703
3	Collaborative Neuroscience Network	Garden Grove	California	United States	92845
4	South Coast Clinical Trials	Norwalk	California	United States	90650
5	CNRI-San Diego	San Diego	California	United States	92102
6	Neuropsychiatric Research Center of Orange County	Santa Ana	California	United States	92701
7	Comprehensive Clinical Development	Washington	District of Columbia	United States	20016
8	Accurate Clinical Trials	Kissimmee	Florida	United States	34741
9	Compass Research, LLC	Orlando	Florida	United States	32806
10	St. Louis Clinical Trials	St. Louis	Missouri	United States	63118
11	Community Clinical Research	Austin	Texas	United States	78754
12	Pillar Clinical Research	Dallas	Texas	United States	75243

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

• Study Director: Stacy Wu, MD, Otsuka Pharmaceutical Development and Commercialization

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT01552772
• Other Study ID Numbers: 31-11-289
• First Posted: Mar 13, 2012
• Last Update Posted: Oct 10, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Safety; Tolerability; Schizophrenia; Aripiprazole
• Additional relevant MeSH terms: Schizophrenia; Aripiprazole

Study Results

Participant Flow

Recruitment Details	Trial to assess the safety and tolerability of aripiprazole intramuscular (IM) depot as an adjunctive therapy in adults with schizophrenia who were stabilized on any one of the atypical oral antipsychotics other than aripiprazole. In the United States, the trial was conducted in 60 enrolled participants and were screened in 12 centres.
Pre-assignment Detail	The study consisted of a 30-day Screening period, a treatment phase of 28 days, and a Follow-up at 30 days after the last trial visit. Participants must have been stabilized on one of the following atypical oral antipsychotic medications for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone.

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Period Title: Overall Study
STARTED	60
COMPLETED	56
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Overall Participants	60
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.2 (10.7)
Sex: Female, Male (Count of Participants)
Female	10 (33.0) 16.7%
Male	50 (67.0) 83.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AE).
Description	An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug related by the study physician. A serious adverse event (SAE) was any untoward medical occurrence that resulted in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. TEAE stands for treatment emergent adverse events.
Time Frame	From the time the informed consent (ICF) was signed until follow-up at 30 days after the last trial visit (Day 28).

Outcome Measure Data

Analysis Population Description

The safety analyses dataset consisted of data from all enrolled participants who received one dose of trial medication, regardless of any protocol deviation. All observed data for these participants were included.

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Participants with TEAE	35 58.3%
Participants with serious TEAE	1 1.7%

2. Secondary Outcome

Title	Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Observed Cases (OC) Data.
Description	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame	Baseline, Week 1, 2, 4 and Last visit (Day 28).

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who had at least one efficacy measurement. The OC dataset are participants who were evaluated at that visit on the efficacy variable under analysis (i.e. participants who had missing data due to drop out or other reasons were not included in the OC dataset).

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	-2.42 (5.57)
Week 2 (N= 56)	-2.86 (7.98)
Week 4 (N= 57)	-3.82 (8.34)
Last visit (N= 59)	-3.68 (8.26)

3. Secondary Outcome

Title	Change From Baseline in Total Score of PANSS for Last Observation Carried Forward (LOCF) Data.
Description	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame	Baseline, Week 1, 2 and 4

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who have at least one efficacy measurement. The LOCF method was used to impute missing data at visits after Baseline for the efficacy analysis and for the safety extrapyramidal symptoms (EPS) assessment scales.

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	-2.42 (5.91)
Week 2 (N= 59)	-2.80 (7.83)
Week 4 (N= 59)	-3.68 (8.26)

4. Secondary Outcome

Title	Change From Baseline in PANSS Positive Sub-scale Score for OC Data.
Description	The Positive and Negative Syndrome Scale (PANSS) consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame	Baseline, Week 1, 2, 4 and Last visit (Day 28).

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who had at least one efficacy measurement. The OC dataset are participants who were evaluated at that visit on the efficacy variable under analysis (i.e. participants who had missing data due to drop out or other reasons were not included in the OC dataset).

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	-0.81 (2.45)
Week 2 (N= 56)	-0.79 (3.37)
Week 4 (N= 57)	-1.28 (2.89)
Last visit (N= 59)	-1.25 (2.84)

5. Secondary Outcome

Title	Change From Baseline in PANSS Positive Sub-scale Score for LOCF Data.
Description	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame	Baseline, Week 1, 2 and 4

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who have at least one efficacy measurement. The LOCF method was used to impute missing data at visits after Baseline for the efficacy analysis and for the safety EPS assessment scales.

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	-0.81 (2.45)
Week 2 (N= 59)	-0.78 (3.29)
Week 4 (N= 59)	-1.25 (2.84)

6. Secondary Outcome

Title	Change From Baseline in PANSS Negative Sub-scale Score for OC Data.
Description	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame	Baseline, Week 1, 2, 4 and Last visit (Day 28).

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who had at least one efficacy measurement. The OC dataset are participants who were evaluated at that visit on the efficacy variable under analysis (i.e. participants who had missing data due to drop out or other reasons were not included in the OC dataset).

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	-0.78 (2.30)
Week 2 (N= 56)	-1.14 (2.88)
Week 4 (N= 57)	-0.96 (2.88)
Last visit (N= 59)	-0.92 (2.84)

7. Secondary Outcome

Title	Change From Baseline in PANSS Negative Sub-scale Score for LOCF Data.
Description	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame	Baseline, Week 1, 2 and 4

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who have at least one efficacy measurement. The LOCF method was used to impute missing data at visits after Baseline for the efficacy analysis and for the safety EPS assessment scales.

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	-0.78 (2.30)
Week 2 (N= 59)	-1.08 (2.82)
Week 4 (N= 59)	-0.92 (2.84)

8. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression Severity (CGI-S) Score in OC Data.
Description	The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not 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, Week 1, 2, 4 and Last visit (Day 28).

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who had at least one efficacy measurement. The OC dataset are participants who were evaluated at that visit on the efficacy variable under analysis (i.e. participants who had missing data due to drop out or other reasons were not included in the OC dataset).

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	0.02 (0.39)
Week 2 (N= 56)	-0.09 (0.35)
Week 4 (N= 57)	-1.14 (0.64)
Last visit (N= 59)	-1.14 (0.63)

9. Secondary Outcome

Title	Change From Baseline in CGI-S Score in LOCF Data.
Description	The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not 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, Week 1, 2 and 4.

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who have at least one efficacy measurement. The LOCF method was used to impute missing data at visits after Baseline for the efficacy analysis and for the safety EPS assessment scales.

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	0.02 (0.39)
Week 2 (N= 59)	-0.08 (0.34)
Week 4 (N= 59)	-0.14 (0.63)

10. Secondary Outcome

Title	Clinical Global Impression Improvement (CGI-I) Scale Score in OC Data.
Description	The efficacy of trial medication were rated for each participant using the CGI-I scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition a 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	Week 1, 2, 4 and Last visit (Day 28).

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who had at least one efficacy measurement. The OC dataset are participants who were evaluated at that visit on the efficacy variable under analysis (i.e. participants who had missing data due to drop out or other reasons were not included in the OC dataset).

Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	3.85 (0.45)
Week 2 (N= 56)	3.70 (0.57)
Week 4 (N= 57)	3.56 (0.78)
Last visit (N= 59)	3.58 (0.77)

11. Secondary Outcome

Title	CGI-I Scale Score in LOCF Data.
Description	The efficacy of trial medication were rated for each participant using the Clinical Global Impression Improvement (CGI-I) scale. The study physician must rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition a 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	Week 1, 2 and 4

Outcome Measure Data

Analysis Population Description

The efficacy analyses dataset consisted of enrolled participants who have at least one efficacy measurement. The LOCF method was used to impute missing data at visits after Baseline for the efficacy analysis and for the safety EPS assessment scales.

Arm/Group Title	Total
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
Measure Participants	60
Week 1 (N= 59)	3.85 (0.45)
Week 2 (N= 59)	3.69 (0.56)
Week 4 (N= 59)	3.58 (0.77)

Adverse Events

Time Frame	From the time the ICF was signed until follow-up at 30 days after the last trial visit (Day 28).
Adverse Event Reporting Description	SAE was any untoward medical occurrence that resulted in death, life-threatening, required inpatient hospitalization or prolonged hospitalization. AE was an exacerbation of an existing problem, any new problem, experienced by a participant in a trial, whether or not considered drug related by study physician.
Arm/Group Title	Aripiprazole IM Depot 400mg
Arm/Group Description	Participants were stabilized on one of the following atypical oral antipsychotic medication for at least 14 days before Day 1: risperidone, quetiapine, olanzapine, ziprasidone, or paliperidone. On Day 1, participants were administered a single aripiprazole IM depot 400 mg injection. Concomitant to the aripiprazole IM depot injection, participants continued to receive their current atypical antipsychotic medication for 14 days.
All Cause Mortality
	Aripiprazole IM Depot 400mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aripiprazole IM Depot 400mg
	Affected / at Risk (%)	# Events
Total	1/60 (1.7%)
Psychiatric disorders
Suicide Attempt	1/60 (1.7%)
Other (Not Including Serious) Adverse Events
	Aripiprazole IM Depot 400mg
	Affected / at Risk (%)	# Events
Total	35/60 (58.3%)
Gastrointestinal disorders
Constipation	1/60 (1.7%)
Diarrhoea	1/60 (1.7%)
Dry mouth	1/60 (1.7%)
Dyspepsia	1/60 (1.7%)
Gastritis	1/60 (1.7%)
Salivary hypersecretion	2/60 (3.3%)
Toothache	4/60 (6.7%)
Vomiting	1/60 (1.7%)
General disorders
Chest pain	1/60 (1.7%)
Fatigue	3/60 (5%)
Injection site pain	4/60 (6.7%)
Irritability	1/60 (1.7%)
Malaise	1/60 (1.7%)
Oedema peripheral	1/60 (1.7%)
Infections and infestations
Nasopharyngitis	1/60 (1.7%)
Tooth abscess	1/60 (1.7%)
Upper respiratory tract infection	1/60 (1.7%)
Injury, poisoning and procedural complications
Procedural pain	1/60 (1.7%)
Thermal burn	1/60 (1.7%)
Investigations
Blood creatine phosphokinase increased	3/60 (5%)
Gamma-glutamyltransferase increased	1/60 (1.7%)
Heart rate increased	1/60 (1.7%)
Weight increased	1/60 (1.7%)
Metabolism and nutrition disorders
Decreased appetite	2/60 (3.3%)
Increased appetite	1/60 (1.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/60 (1.7%)
Costochondritis	1/60 (1.7%)
Joint stiffness	2/60 (3.3%)
Muscle spasms	1/60 (1.7%)
Muscular weakness	1/60 (1.7%)
Musculoskeletal pain	2/60 (3.3%)
Musculoskeletal stiffness	1/60 (1.7%)
Neck pain	1/60 (1.7%)
Osteoarthritis	1/60 (1.7%)
Nervous system disorders
Akathisia	2/60 (3.3%)
Disturbance in attention	1/60 (1.7%)
Dizziness	1/60 (1.7%)
Dystonia	3/60 (5%)
Extrapyramidal disorder	1/60 (1.7%)
Headache	1/60 (1.7%)
Sedation	1/60 (1.7%)
Tremor	2/60 (3.3%)
Psychiatric disorders
Impatience	1/60 (1.7%)
Insomnia	3/60 (5%)
Restlessness	3/60 (5%)
Renal and urinary disorders
Proteinuria	1/60 (1.7%)
Pyuria	1/60 (1.7%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/60 (1.7%)
Cough	1/60 (1.7%)
Nasal congestion	1/60 (1.7%)
Skin and subcutaneous tissue disorders
Rash	1/60 (1.7%)
Skin discolouration	1/60 (1.7%)
Skin nodule	1/60 (1.7%)
Vascular disorders
Hypertension	1/60 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.