An Open Label Study of Aripiprazole Intramuscular Injection in Subjects With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to determine whether aripiprazole injection into the shoulder or the buttocks produces similar effects in the body

Detailed Description
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Extended-release gluteal intramuscular (IM) injection of aripiprazole has been tested in subjects with schizophrenia for safety and tolerability. This study will compare the gluteal IM aripiprazole injection with deltoid IM aripiprazole injection for safety and tolerability.

Official Title
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An Open-label, Randomized, Parallel Arm, Bioavailability Trial of Aripiprazole IM Depot Administered in the Deltoid or Gluteal Muscle in Adult Subjects With Schizophrenia

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: Diagnosis of schizophrenia Stabilized on oral antipsychotic medication Good physical health BMI 18 to 35 kg/m2 Prior history of tolerating aripiprazole 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. 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). Use of any psychotropic medications other than their current antipsychotic medication. Use of any CYP2D6 and CYP3A4 inhibitors, or CYP3A4 inducers within 14 days (fluoxetine 28 days) prior to dosing and for the duration of the trial. Females who are pregnant or lactating. Subjects who had participated in a previous IM depot trial within the last one year; 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, routine psychiatric status examination, investigator's judgment, or who have an answer of yes on questions 4 or 5 (current or over the last 30 days) on the Baseline/Screening version of the Columbia Suicide Severity Rating Scale (C-SSRS). 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 who have had electroconvulsive therapy within 2 months of administration of trial drug. Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia as assessed by the investigator. Any other sound medical reason not to be entered into the trial, as determined by the clinical investigator. 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Aripriprazole | Relative bioavailability (Frel) of aripiprazole intramuscular (IM) depot injected in the deltoid muscle compared to the gluteal muscle based on aripiprazole maximum (peak) plasma concentrations (Cmax) PK parameter. | Day 1: 4 hr, 8 hr, and 12 hr post dose, Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112 and 126/Early termination | 
| Area Under the Concentration-Time Curve Infinity (AUC Infinity); Area Under the Concentration-Time Curve 28 (AUC 28), and Area Under the Concentration-Time Curve t (AUC t): Aripiprazole | Relative bioavailability (Frel) of aripiprazole IM depot injected in the deltoid muscle compared to the gluteal muscle based on area under the concentration-time curve (AUC) from time zero to the time of last measurable concentration (AUCt), AUC time curve 28, and AUC from time zero to infinity PK parameters. | Day 1: 4 hr, 8 hr, and 12 hr post dose, Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112 and 126/Early termination | 
| Maximum Observed Plasma Concentration (Cmax) of Dehydro-Aripiprazole | Relative bioavailability (Frel) of aripiprazole intramuscular (IM) depot injected in the deltoid muscle compared to the gluteal muscle based on aripiprazole maximum (peak) plasma concentrations (Cmax) PK parameter. | Day 1: 4 hr, 8 hr, and 12 hr post dose, Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112 and 126/Early termination | 
| Area Under the Concentration-Time Curve Infinity (AUC Infinity); Area Under the Concentration-Time Curve 28 (AUC 28), and Area Under the Concentration-Time Curve t (AUC t): Dehydro-Aripiprazole | Relative bioavailability (Frel) of aripiprazole IM depot injected in the deltoid muscle compared to the gluteal muscle based on area under the concentration-time curve (AUC) from time zero to the time of last measurable concentration (AUCt), AUC time curve 28 and AUC from time zero to infinity PK parameters. | Day 1: 4 hr, 8 hr, and 12 hr post dose, Days 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 25, 28, 35, 42, 49, 56, 63, 70, 77, 84, 98, 112 and 126/Early termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Treatment Emergent Adverse Events (TEAE). | Safety was measured according to standard adverse event collection as described in the adverse event section of the results. | Starting at the time the ICF was signed to Day 126/Early termination | 
| Number of Participants With Laboratory Values of Potential Clinical Relevance. | The laboratory tests were collected and processed in accordance with directions from the clinical chemistry laboratory. Based on criteria for identifying laboratory values of potential clinical relevance, the abnormal values were noted. Some of the criteria are as follows: For fasting triglycerides: men: ≥ 160 mg/dL and women: ≥ 120 mg/dL; Fasting glucose: ≥ 115 mg/dL; Prolactin: > upper limit of normal (ULN); Neutrophils: ≤ 1,500/mm3; and Creatine phosphokinase: ≥ 3 x ULN. | Day 1, Day 28, Day 126/Early termination | 
| Number of Participants With Vital Signs of Potential Clinical Relevance-Blood Pressure | Vital sign assessment included orthostatic (supine and standing) blood pressure. Orthostatic assessments were made after participants had been in the supine position for at least 5 minutes and again after participants had been standing for 2 minutes, but not more than 3 minutes. Orthostatic hypotension defined as >/= 20 mm Hg decrease in systolic blood pressure and >/= 25 beats per minute increase in heart rate from supine to standing. | Day 1, Day 14, Day 28 and Day 126/Early termination | 
| Number of Participants With Vital Signs of Potential Clinical Relevance-Temperature | Vital sign assessment included body temperature measured in centigrade(C). Temperatures >=37.8°C and increase of >= 1.1°C were recorded. | Day 1, Day 14, Day 28 and Day 126/Early termination | 
| Number of Participants With Vital Signs of Potential Clinical Relevance-Heart Rate | Vital sign assessment included heart rate (supine and standing). Heart rate with increase or decrease of >/= 15 beats per minute were recorded. | Day 1, Day 14, Day 28 and Day 126/Early termination | 
| Number of Participants With Electrocardiogram (ECG) Measurements of Potential Clinical Relevance | Three 12 lead ECGs were performed approximately 5 minutes apart at each time point. The participant were supine and at rest (for at least 10 minutes) prior to the first ECG and will remain supine through the final ECG. Based on criteria for identifying ECG measurements of potential clinical relevance, the abnormal values were noted. Some of the criteria are as follows: For bradycardia: ≤ 50 beats per minute (bpm); and for increase in QTc: QTc ≥ 450msec. | Day 1, Day 14, Day 28 and Day 126/Early termination | 
| Visual Analog Scale (VAS) Score at Day 1, Day 14, Day 28 and Last Visit. | Injection site pain was assessed using a VAS, which was completed by the trial participant, and the investigator's assessment of most recent injection site, which was completed by the investigator. VAS is 100 mm line, 0=no pain, 100=unbearably painful. | Day 1, Day 14, Day 28 and last visit | 
| Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale. | This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post baseline evaluation that focuses on suicidality since the last trial visit. | Screening, Baseline, Week 1, Week 2, Week 8, Week 18 visit and Last visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, extended release antipsychotic