Trial of Aripiprazole Intramuscular Depot (OPC-14597, Lu... | NCT01663532

NCT01663532

Status Module

Sponsor/Collaborators Module

Name	Class
H. Lundbeck A/S	INDUSTRY
Otsuka America Pharmaceutical	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Aripiprazole IM Depot	Experimental	Aripiprazole IM Depot 400 mg, with allowed decrease to 300 mg for safety and return to 400 mg for efficacy if needed, every four weeks for 12 weeks	Drug: Aripiprazole IM Depot
Placebo	Placebo Comparator	Matching placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Aripiprazole IM Depot	Drug		Aripiprazole IM Depot	OPC-14597 Lu AF41155

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline to Endpoint in Positive and Negative Syndrome Scale (PANSS) Total Score.	The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 that indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The PANSS total score was the sum of the rating scores for 7 positive subscale items, 7 negative subscale items, and 16 general psychopathology subscale items from the PANSS panel. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome). The primary statistical comparison was performed using the Mixed Model Repeated Measure (MMRM) approach.	Baseline to Week 10

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score.	The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: "Considering your total experience with this particular population, how mentally ill is the patient at this time?" Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.
Subjects with a diagnosis of schizophrenia for at least 1 year as defined by DSM-IV-TR criteria and confirmed by the MINI for Schizophrenia and Psychotic Disorders Studies.
Subjects with a stable living environment when not in hospital.
Subjects who would benefit from hospitalization or continued hospitalization for treatment of a current acute relapse of schizophrenia at trial entry.
Subjects who are experiencing an acute exacerbation of psychotic symptoms and marked deterioration of usual function as demonstrated by meeting BOTH of the following at screening and baseline:
- Currently experiencing an acute exacerbation of psychotic symptoms accompanied by significant deterioration in the subject's clinical and/or functional status from their baseline clinical presentation with a Positive and Negative Syndrome Scale (PANSS) Total Score ≥ 80 AND
- Specific psychotic symptoms on the PANSS as measured by a score of > 4 on each of the following items (possible scores of 1 to 7 for each item)
  - Conceptual disorganization (P2)
  - Hallucinatory behavior (P3)
  - Suspiciousness/persecution (P6)
  - Unusual thought content (G9)
Subjects who have received previous outpatient antipsychotic treatment at an adequate dose for an adequate duration and who showed a previous good response to such antipsychotic treatment (other than clozapine) in last 12 months.
Subjects with a history of relapse and/or exacerbation of symptoms when not receiving antipsychotic treatment, excluding current episode.
Subjects willing to discontinue all prohibited psychotropic medications to meet protocol required washouts prior to and during trial period.
BMI less ≤ 40 kg/m2 (morbid obesity) at screening.
Subjects who are able to provide written informed consent.
Ability to understand the nature of trial and follow protocol requirements.

Exclusion Criteria:

Sexually active males of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 180 days after last dose of trial medication. Sexually active females of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 150 days after last dose of trial medication.
Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP in this trial.
Subjects with improvement of ≥ 30% in total PANSS score between the screening and baseline assessments. - Subjects presenting with a first episode of schizophrenia - Subjects hospitalized for ≥ 30 days out of the last 90 days prior to screening visit. Subjects who have been hospitalized > 5 days for current acute episode at the time of screening visit
Subjects with schizophrenia who are considered resistant/refractory to antipsychotic treatment Subjects who have a history of response to clozapine treatment only.
Subjects with a current DSM-IV-TR Axis I diagnosis other than schizophrenia Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder or mental retardation.
Subjects experiencing acute depressive symptoms within past 30 days that require treatment with an antidepressant.
Subjects with a significant risk of violent behavior; who represent a risk of committing suicide as indicated by any suicidal ideation within the last 1 month or any suicidal behaviors within the last year; or who present a serious risk of suicide.
Subjects with clinically significant tardive dyskinesia,.
Subjects with severe akathisia.
Subjects who have met DSM-IV-TR criteria for substance abuse with past 3 months prior to screening or dependence within past 6 months; including alcohol and benzodiazepines, but excluding caffeine and nicotine.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
		Little Rock	Arkansas	72201	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
42138587	Derived	Citrome L, Bell Lynum KS, Zhang Z, Atkins N Jr, Hutson Walker AM, Yildirim M. Aripiprazole Once-Monthly for Patients Diagnosed With Schizophrenia: Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. J Clin Psychiatry. 2026 May 13;87(2):26m16359. doi: 10.4088/JCP.26m16359.
25188501	Derived

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).
BG001	Placebo	Participants randomized to Placebo group received matching placebo. For 14 days beginning with the first injection, participants received concomitant oral placebo.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Week 1 (N= 162, 167)

Title	Measurements
	OG000-8.9± 0.9 OG001-5.0± 0.9

Week 2 (N= 144, 157)

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis of change from Baseline in PANSS total score of aripiprazole IM depot 400/300mg group is same as that of placebo group was tested. The sample size estimated a 1:1 randomization ratio (aripiprazole IM depot 400/300mg: placebo) to achieve 90% power and to preserve a nominal alpha level of 0.05 given a treatment difference of -7.5 points in change from Baseline with standard deviation of 20 points between aripiprazole and placebo using a two-sided z-test.	Mixed Models Analysis	MMRM analysis with treatment, pooled centers, Week and treatment-by-Week, and Baseline-by-Week interaction as an unstructured covariate was performed.	0.0005	Kenward-Rodger degree of freedom was used to test the treatment effects and p-value was not adjusted as this is a primary efficacy endpoint.	Mean Difference (Final Values)	-3.9			2-Sided	95	-6.1	-1.7

Secondary

Mean Change From Baseline to Endpoint in Clinical Global Impression-Severity Scale (CGI-S) Score.

The severity of illness for each participants were rated using the CGI-S scale. The study physician were to answer the following question: "Considering your total experience with this particular population, how mentally ill is the patient at this time?" Response choices included were: 0= not assessed; 1= normal; not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.

Efficacy sample was defined as the intent to treat (ITT) population which included randomized participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had at least one Post-Baseline efficacy assessment. Data of only 162 and 168 participants from aripiprazole and placebo groups were available.

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline to Week 10

ID	Title	Description
OG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).
OG001

Secondary

Mean Change From Baseline to Endpoint in PANSS Positive Subscale Score.

The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline to Week 10

ID	Title	Description
OG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).

Secondary

Mean Change From Baseline to Endpoint in PANSS Negative Subscale Score.

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 indicated- absence of symptoms and a score of 7 indicated- 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 were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms).

Posted

Least Squares Mean

Standard Error

Units on a scale

Baseline to Week 10

ID	Title	Description
OG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).

Secondary

Mean Change From Baseline to Endpoint in Personal and Social Performance Scale (PSP) Score.

The PSP was a validated clinician scale that measured personal and social functionining in 4 domains: socially useful activities eg, work and study), personal and social relationships, self-care, disturbing and aggressive behaviours. Impairement in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval and the study physician's judgement to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented varying degrees of disability (31 to 70) and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision.

Efficacy sample included participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had one Post-Baseline efficacy assessment. LOCF was used to impute the missing data with the recorded value obtained at the preceding visit.

Posted

Least Squares Mean

Standard Error

Units on a scale

Week 10

ID	Title	Description
OG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).

Secondary

Mean Clinical Global Impression-Improvement Scale (CGI-I) Score at Endpoint.

Efficacy sample was defined as the ITT population which included randomized participants who took at least one injection of double-blind (aripiprazole IM depot or placebo) and had at least one Post-Baseline efficacy assessment. LOCF was used to impute the missing data with the recorded value obtained at the preceding visit.

Posted

Mean

Standard Deviation

Units on a scale

Week 10

ID	Title	Description
OG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).
OG001	Placebo

Secondary

Responder Rate Based on PANSS Total Score.

Responder rate was defined as ≥30% reduction from Baseline in PANSS Total Score. PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

Posted

Number

participants

Week 10

ID	Title	Description
OG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).
OG001	Placebo	Participants randomized to Placebo group received matching placebo. For 14 days beginning with the first injection, participants received concomitant oral placebo.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Aripiprazole IM Depot 400/300mg	Participants randomized to aripiprazole IM depot received aripiprazole IM depot 400 mg as the initial dose with a single decrease to aripiprazole IM depot 300 mg permitted for tolerability per the study physician. The study treatment was injected into gluteal muscle every 4 weeks (Baseline/Day, Week 4, Week 8) during the 12-Week Acute Treatment Phase (ie, 3 IM depot injections). For 14 days beginning with the first injection, participants received concomitant oral aripiprazole (10 to 20 mg/day based on the study physician's clinical judgment).			8	167	91	167
EG001	Placebo	Participants randomized to Placebo group received matching placebo. For 14 days beginning with the first injection, participants received concomitant oral placebo.			6	172	68	172

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 affected167 at risk EG0010 affected172 at risk
Agitation	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 affected167 at risk EG0010 affected172 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0002 affected167 at risk EG0012 affected172 at risk
Schizophrenia	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0003 affected167 at risk EG0013 affected172 at risk
Substance abuse	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 affected167 at risk EG0010 affected172 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 affected167 at risk EG0010 affected172 at risk
Hypotension	Vascular disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 affected167 at risk EG0011 affected172 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG00016 affected167 at risk EG00112 affected172 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG00010 affected167 at risk EG00111 affected172 at risk
Toothache	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0009 affected167 at risk EG0018 affected172 at risk
Injection site pain	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0009 affected167 at risk EG0011 affected172 at risk
Weight increased	Investigations	MedDRA 15.0	Non-systematic Assessment	EG00028 affected167 at risk EG00112 affected172 at risk
Akathisia	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG00019 affected167 at risk EG0016 affected172 at risk
Headache	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG00024 affected167 at risk EG00128 affected172 at risk
Sedation	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0009 affected167 at risk EG0012 affected172 at risk
Agitation	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0009 affected167 at risk EG00111 affected172 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Non-systematic Assessment	EG00010 affected167 at risk EG00110 affected172 at risk

ID	Term
D012559	Schizophrenia

ID	Term
D000068180	Aripiprazole

Ancestor Terms

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

Units	Counts
Participants	OG000162 OG001168

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