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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Aripiprazole IM Depot


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female individuals between 18 and 64 years of age, inclusive, with a diagnosis of schizophrenia as defined by DSM-IV-TR criteria. Good physical health as determined by no clinically significant deviation from normal in medical history, clinical laboratory determination, ECGs, or physical examinations. 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. Body mass index of 18 to 35 kg/m2, inclusive. Prior history of tolerating aripiprazole. 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: 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. 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 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. Females who are pregnant or lactating. 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. Any major surgery within 30 days prior to enrollment. Evidence of organ dysfunction or any clinically significant deviation from normal in physical, electrocardiographic, or clinical laboratory examinations. Subjects who have a significant risk of committing suicide based on history or routine psychiatric status examination Subjects currently in an acute relapse of schizophrenia. 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. Subjects who were considered treatment-resistant to antipsychotic medication. (Subjects needed to have shown a previous response to an antipsychotic medication other than clozapine.) Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia. Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aripiprazole IM Depot<br> | Drug: Aripiprazole IM Depot<br>* 400 mg intramuscular injection of aripiprazole<br>* Other names: Abilify;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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. | From the time the informed consent (ICF) was signed until follow-up at 30 days after the last trial visit (Day 28). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Score of Positive and Negative Syndrome Scale (PANSS) for Observed Cases (OC) Data. | 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). | Baseline, Week 1, 2, 4 and Last visit (Day 28). | 
| Change From Baseline in Total Score of PANSS for Last Observation Carried Forward (LOCF) Data. | 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). | Baseline, Week 1, 2 and 4 | 
| Change From Baseline in PANSS Positive Sub-scale Score for OC Data. | 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). | Baseline, Week 1, 2, 4 and Last visit (Day 28). | 
| Change From Baseline in PANSS Positive Sub-scale Score for LOCF Data. | 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). | Baseline, Week 1, 2 and 4 | 
| Change From Baseline in PANSS Negative Sub-scale Score for OC Data. | 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). | Baseline, Week 1, 2, 4 and Last visit (Day 28). | 
| Change From Baseline in PANSS Negative Sub-scale Score for LOCF Data. | 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). | Baseline, Week 1, 2 and 4 | 
| Change From Baseline in Clinical Global Impression Severity (CGI-S) Score in OC Data. | 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. | Baseline, Week 1, 2, 4 and Last visit (Day 28). | 
| Change From Baseline in CGI-S Score in LOCF Data. | 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. | Baseline, Week 1, 2 and 4. | 
| Clinical Global Impression Improvement (CGI-I) Scale Score in OC Data. | 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. | Week 1, 2, 4 and Last visit (Day 28). | 
| CGI-I Scale Score in LOCF Data. | 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. | Week 1, 2 and 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Tolerability, Schizophrenia, Aripiprazole