A Multiple Dose Safety, Tolerability and Pharmacokinetics... | NCT01870999

Label	Type	Description	Intervention Names
400 mg Aripiprazole IM Depot	Experimental	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.	Drug: aripiprazole IM depot Drug: aripiprazole tablets
300 mg Aripiprazole IM Depot	Experimental	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.	Drug: aripiprazole IM depot Drug: aripiprazole tablets
200 mg Aripiprazole IM depot	Experimental	200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.	Drug: aripiprazole IM depot Drug: aripiprazole tablets

Name	Type	Description	Arm Group Labels	Other Names
aripiprazole IM depot	Drug	Aripiprazole IM depot supplied as 200 mg or 400 mg vials of lyophilized aripiprazole powder to prepare for IM injection.	200 mg Aripiprazole IM depot

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events as a Measure of Safety	Safety and tolerability was assessed by the number of participants with adverse events (AE). An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a subject while enrolled in the study, whether or not it was considered drug-related by the investigator. Abnormal laboratory test findings were considered AEs if, in the opinion of the investigator, they represented an abnormal (ie, clinically significant) change from baseline for that individual participant.	7 Months
Aripiprazole Maximum Steady State Plasma Concentration (Css,Max)	Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,max were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.	Pre-dose and 1 to 1344 hours post-dose at Month 5
Aripiprazole Minimum Steady State Plasma Concentration (Css,Min)	Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,min were determined directly from the observed data at 672 hours after the fifth monthly injection.	672 hours post-dose at Month 5
Aripiprazole Area Under the Concentration-time Curve at Steady-state (AUCτ)	Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values of AUCτ were estimated using the linear trapezoidal rule during each dosing interval from 0 to 1344 hours post-dose.	Pre-dose and 1 to 1344 hours post-dose at Month 5

Secondary Outcomes

Measure	Description	Time Frame
Aripiprazole Maximum (Peak) Plasma Concentration (Tmax)	Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for tmax were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria
good physical health as determined by normal medical history, clinical laboratory results, electrocardiograms (ECGs) and physical examinations
ability to provide informed consent and/or consent from a legally acceptable representation
body mass index (BMI) of 18 to 35 kg/m^2

Exclusion Criteria:

sexually active males and females of child-bearing potential who are not practicing double barrier birth control or are not abstinent during the study plus 30 days for female or 90 days for males following the last dose of medication
history of drug or alcohol abuse within 6 months and/or positive urine drug screen
participants who consume alcohol beverages routinely
participants who consume alcohol beverages during the screening period
use of any antipsychotic medication, other prohibited psychotropic medication, and any cytochrome P450 2D6 (CYP2D6) and cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 inducers within 14 days
use of any prescription medication unless approved by Medical Monitor or Study Director
history of current hepatitis or carrier of HBsAg (Hepatitis B surface antigen) and/or Hepatitis C Virus antibodies (anti-HCV)
females who are pregnant or lactating
participants who have participated in any clinical trial involving a psychotropic medication within one month prior to enrollment; participants who have participated in a previous IM Depot study within the last 1 year; patients who have previously enrolled and received study medication in an aripiprazole IM Depot clinical trial
donation of blood or plasma to a blood bank or in a clinical study (except a screening visit)within 30 days prior to enrollment
any major surgery within 30 days prior to enrollment
blood transfusion within 30 days prior to enrollment
evidence of organ dysfunction or any clinically significant deviation from normal in the physical, electrocardiographic, or clinical laboratory examinations
patient represents a significant risk of committing suicide based on history
patients currently in an acute relapse
patients with Axis I (DSM-IV) diagnosis of schizoaffective or bipolar disorder
patients who are considered treatment-resistant to antipsychotic medication
patients with a history of neuroleptic malignant syndrome
any other sound medical reason as determined by the clinical investigator

Facility	Status	City	State	ZIP	Country	Contacts
Otsuka Investigative Site		Cerritos	California	90703	United States
Otsuka Investigative Site

ID	Title	Description
FG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

ID	Title	Description
BG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
BG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
BG002	200 mg Aripiprazole IM Depot	200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00014 BG00116 BG00211 BG00341

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Adverse Events as a Measure of Safety

Safety and tolerability was assessed by the number of participants with adverse events (AE). An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a subject while enrolled in the study, whether or not it was considered drug-related by the investigator. Abnormal laboratory test findings were considered AEs if, in the opinion of the investigator, they represented an abnormal (ie, clinically significant) change from baseline for that individual participant.

Participants who received at least one dose of study medication are included in the safety analysis set.

Posted

Number

Participants

7 Months

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG002	200 mg Aripiprazole IM Depot	200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Units	Counts
Participants	OG00014 OG00115 OG00210

Title

Denominators

Categories

Title	Measurements
	OG00011 OG00111 OG0026

Primary

Aripiprazole Maximum Steady State Plasma Concentration (Css,Max)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,max were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

Participants who received at least 3 doses of study medication and had pharmacokinetic (pK) samples collected through at least 672 hours following the 5th dose are included in the efficacy pK analysis set.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Primary

Aripiprazole Minimum Steady State Plasma Concentration (Css,Min)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,min were determined directly from the observed data at 672 hours after the fifth monthly injection.

Posted

Mean

Standard Deviation

ng/mL

672 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Primary

Aripiprazole Area Under the Concentration-time Curve at Steady-state (AUCτ)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values of AUCτ were estimated using the linear trapezoidal rule during each dosing interval from 0 to 1344 hours post-dose.

Participants who received at least 3 doses of study medication and had pharmacokinetic (pK) samples collected through at least 672 hours following the 3rd or 4th dose are included in the efficacy pK analysis set. Data was missing for 1 patient in the 300 mg Aripiprazole IM Depot arm.

Posted

Mean

Standard Deviation

μg*h/mL

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Aripiprazole Maximum (Peak) Plasma Concentration (Tmax)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for tmax were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

Participants who received study medication and had pharmacokinetic (pK) samples collected through at least 672 hours following the 5th dose are included in the efficacy pK analysis set.

Posted

Median

Full Range

Day

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Aripiprazole Steady-state Plasma Concentration (Css,Avg)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for Css,avg were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

Participants who received study medication and had pharmacokinetic (pK) samples collected through at least 672 hours following the 5th dose are included in the efficacy pK analysis set. Data was missing for 1 patient in the 300 mg Aripiprazole IM Depot arm.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Aripiprazole Terminal-phase Elimination Half-life (t1/2,z)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for aripiprazole. Values for t1/2,z were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

Participants who received at least 3 doses of study medication and had pharmacokinetic (pK) samples collected through at least 672 hours following the 3rd or 4th dose are included in the efficacy pK analysis set. The analysis population for this outcome measure represents a sub-set who were evaluable for this measure at month 5.

Posted

Mean

Standard Deviation

Day

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Dehydro-aripiprazole Maximum Steady State Plasma Concentration (Css,Max)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for dehydro-aripiprazole. Values for Css,max were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Dehydro-aripiprazole Minimum Steady State Plasma Concentration (Css,Min)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for dehydro-aripiprazole. Values for Css,min were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Dehydro-aripiprazole Area Under the Concentration-Time Curve at Steady-State (AUCτ)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for dehydro-aripiprazole. Values of AUCτ were estimated using the linear trapezoidal rule during each dosing interval from 0 to 1344 hours post-dose.

Posted

Mean

Standard Deviation

μg*h/mL

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Dehydro-aripiprazole Maximum (Peak) Plasma Concentration (Tmax)

Blood samples were collected for pharmacokinetic parameters pre-dose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, 264, 336, 504, 672, 1008 and 1344 hours post-dose and were analyzed for dehydro-aripiprazole. Values for tmax were determined directly from the observed data during the dosing interval (0-1344 hours) after the fifth monthly injection.

Posted

Median

Full Range

Day

Pre-dose and 1 to 1344 hours post-dose at Month 5

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 and Week 24

The PANSS consisted of 3 subscales with a total of 30 symptom constructs each rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The Positive Subscale consisted of 7 positive symptom constructs with a possible subscale score of 7 to 49, the Negative Subscale consisted of 7 negative symptom constructs with a possible subscale score of 7 to 49 and the General Psychopathology Subscale consisted of 16 symptom constructs for a possible subscale score of 16 to 112. The PANSS Total Score ranged from 30 (best) to 210 (worst; indicating more severe symptoms). A Negative change from Baseline indicated improvement.

All randomized participants with data available were included in this analysis population-last observation carried forward (LOCF).

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 12, Week 24

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Positive Subscale Scores at Week 12 and Week 24

The PANSS Positive Subscale consisted of 7 symptom constructs: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Severity was rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The total score on the Positive Subscale ranged from 7 to 49 with a higher score indicating more severe symptoms. A Negative change from Baseline indicated improvement.

All randomized participants with data available were included in this analysis population (LOCF).

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 12, Week 24

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Negative Subscale Scores at Week 12 and Week 24

The PANSS Negative Subscale consisted of 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. Severity was rated on a 7-point scale where 1=absence of symptoms to 7=extremely severe symptoms. The total score on the Negative Subscale ranged from 7 to 49 with a higher score indicating more severe symptoms. A negative change from Baseline indicated improvement.

All randomized participants with data available were included in this analysis population (LOCF).

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 12, Week 24

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Change From Baseline in the Clinical Global Impression- Severity of Illness Score (CGI-S) at Week 12 and Week 24

The severity of illness for each participant was rated using the CGI-S scale. The investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" using an 8-point scale where 0=not assessed to 7=among the most extremely ill patients. A negative change from Baseline indicated improvement.

All randomized participants with data available were included in this analysis population (LOCF).

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 12, Week 24

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Clinical Global Impression-Improvement Scale (CGI-I) at Week 12 and Week 24

The participant's overall improvement was rated for each participant using the CGI-I scale. The investigator rated the participant's total improvement by answering the following question: "Compared to his/her condition at baseline (prior to randomization), how much has the patient changed?" using an 8-point scale where 0=not assessed, 1=very much improved to 7=very much worse. Lower scores indicated improvement.

All randomized participants with data available at the given time-point were included in this analysis population.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Week 12, Week 24

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Secondary

Number of Participants Hospitalized for Adverse Event "Worsening Schizophrenia"

The number of participants hospitalized for the Adverse Event "Worsening Schizophrenia included all participants who were hospitalized for any Adverse Event pertaining to the exacerbation of schizophrenic symptoms.

All randomized participants were included in the analysis population.

Posted

Number

Participants

7 Months

ID	Title	Description
OG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.
OG002	200 mg Aripiprazole IM Depot	200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tachycardia	Cardiac disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Constipation	Gastrointestinal disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Dry Mouth	Gastrointestinal disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Nausea	Gastrointestinal disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0012 affected15 at risk EG0020 affected10 at risk
Salivary hypersecretion	Gastrointestinal disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Toothache	Gastrointestinal disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Vomiting	Gastrointestinal disorders	MedDRA (9.1)	Systematic Assessment	EG0002 affected14 at risk EG0012 affected15 at risk EG0020 affected10 at risk
Cyst	General disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Fatigue	General disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0021 affected10 at risk
Injection site discomfort	General disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Injection site pain	General disorders	MedDRA (9.1)	Systematic Assessment	EG0004 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Pyrexia	General disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Bed bug infestation	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Furuncle	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Infected insect bite	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Influenza	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Nasopharyngitis	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0002 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Sinusitis	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0002 affected14 at risk EG0011 affected15 at risk EG0021 affected10 at risk
Vaginal infection	Infections and infestations	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA (9.1)	Systematic Assessment	EG0002 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Blood glucose increased	Investigations	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Blood magnesium increased	Investigations	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Blood potassium decreased	Investigations	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Cardiac murmur	Investigations	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Electrocardiogram QT corrected interval prolonged	Investigations	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0012 affected15 at risk EG0021 affected10 at risk
Glucose urine present	Investigations	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA (9.1)	Systematic Assessment	EG0002 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Akathisia	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0011 affected15 at risk EG0021 affected10 at risk
Disturbance in attention	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Dizziness	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Dyskinesia	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Dystonia	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Headache	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0022 affected10 at risk
Sedation	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0002 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Somnolence	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0012 affected15 at risk EG0021 affected10 at risk
Tremor	Nervous system disorders	MedDRA (9.1)	Systematic Assessment	EG0003 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Anxiety	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Drug dependence	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Hallucination, auditory	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Hallucination, visual	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Insomnia	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0011 affected15 at risk EG0021 affected10 at risk
Nightmare	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Paranoia	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Restlessness	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (9.1)	Systematic Assessment	EG0001 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (9.1)	Systematic Assessment	EG0002 affected14 at risk EG0010 affected15 at risk EG0020 affected10 at risk
Hypertension	Vascular disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Orthostatic hypotension	Vascular disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk
Psychotic disorder	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0010 affected15 at risk EG0021 affected10 at risk

ID	Term
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D015363	Quinolones
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	400 mg Aripiprazole IM Depot	400 mg aripiprazole IM (intramuscular) depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.	0	14	9	14
EG001	300 mg Aripiprazole IM Depot	300 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.	3	15	10	15
EG002	200 mg Aripiprazole IM Depot	200 mg aripiprazole IM depot intramuscular injection once every 4 weeks for 5 months. All participants were on a stable dose of 10 mg aripiprazole tablets once daily in the morning for at least 14 days prior to randomization and continued 10 mg aripiprazole tablets once daily on days 1 to 14.	0	10	6	10

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest Pain	General disorders	MedDRA 9.1	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Psychotic disorder	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk
Schizophrenia	Psychiatric disorders	MedDRA (9.1)	Systematic Assessment	EG0000 affected14 at risk EG0011 affected15 at risk EG0020 affected10 at risk

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders