Study to Determine the Pharmacokinetics, Safety & Tolerability of Aripiprazole in Adults With Schizophrenia

Study Overview
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Brief Summary
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This trial will determine the Pharmacokinetics, safety and tolerability of single-dose Aripiprazole administered intramuscularly in adults with schizophrenia

Official Title
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A Phase 1, Open-label, Single Ascending Dose, Parallel Arm Trial to Determine the Pharmacokinetics, Safety, and Tolerability of Aripiprazole 2 Month Intramuscular Depot Administered Gluteally in Adult Subjects With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female individuals between 18 and 64 years, inclusive, at screening with a current diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders: edition 5 (DSM-5) Body mass index (BMI) between 18 and 35 kg/m^2 at screening Male and female subjects who are surgically sterile, female subjects who have been postmenopausal for at least 12 consecutive months prior to screening or male/female subjects who agree to remain abstinent or practice 2 of the approved birth control methods from screening for at least 150 days after dose of Investigational Medical Product (IMP) for female subjects or 180 days after dose of IMP for male subjects. Documented history of previously tolerating Aripiprazole per investigator's judgment. Exclusion Criteria: Met DSM-5 criteria for substance use disorder within past 180 days Positive drug screen for drugs of abuse Use of more than 1 antipsychotic medication at screening or baseline, except for oral Aripiprazole administered during tolerability testing and current antipsychotic medication Subjects may not receive varenicline beyond the screening visit. Subjects who had participated in any clinical trial involving a psychotropic medication within 1 month prior to administration of IMP Major surgery within 30 days prior to administration of IMP or surgery during the trial Subjects at significant risk of committing suicide based on history, psychiatric exams Subjects currently in an acute relapse of schizophrenia Subjects with a current DSM-5 diagnosis other than schizophrenia Subjects with a history of neuroleptic malignant syndrome, seizure disorder, or clinically significant tardive dyskinesia Subjects who have had electroconvulsive therapy within 2 months prior to administration of IMP Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP History of or current hepatitis or Acquired Immunodeficiency Syndrome or carriers of Hepatitis B surface antigen (HBsAG), Hepatitis C antigen (anti-HCV) and/or Human Immunodeficiency Virus (HIV) antibodies

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: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Aripiprazole; single; gluteal | Drug: Aripiprazole<br>* Injection<br>* Other names: Abilify Maintena;|
| Experimental: Cohort 2<br>Aripiprazole; single; gluteal | Drug: Aripiprazole<br>* Injection<br>* Other names: Abilify Maintena;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) [safety and tolerability] | AEs will be monitored to assess safety and tolerability of drug | Screening Days -30 to Day 182 post dose/Early Termination | 
| Clinical Laboratory Tests [safety and tolerability] | Hematology, clinical chemistry & urinalysis tests will be performed to assess the safety and tolerability of drug. | Screening Days -30 to Day 182 post dose/Early Termination | 
| Electrocardiograms (ECGs) [Safety and tolerability] | Heart rate, RR, PR, WRS and WT intervals will be monitored to assess the safety and tolerability of the drug. | Screening Days -30 to Day 182 post dose/Early Termination | 
| Vital Signs [safety and tolerability] | Systolic/diastolic blood pressure, heart rate and body temperature will be monitored to assess the safety and tolerability of the drug. | Screening Days -30 to Day 182 post dose/Early Termination | 
| Suicidality via Columbia-Suicide Severity Rating Scale (C-SSRS) [safety and tolerability] | C-SSRS score will be monitored throughout the trial to assess the safety and tolerability of drug | Screening Days -30 to Day 182 post dose/Early Termination | 
| Extrapyramidal Symptoms (EPS) Rating Scales | EPS score will be monitored to assess safety and tolerability of drug | Screening Days -30 to Day 182 post dose/Early Termination | 
| Investigator's Assessment of Injection Site | The injection site will be monitored to assess the safety and tolerability of drug | Screening Days -30 to Day 182 post dose/Early Termination | 
| Visual Analog Scale (VAS) Scores for Pain Perception | VAS score will be monitored to assess safety and tolerability of drug | Day 1 to Day 28 post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics - Maximum plasma concentration (Cmax) | The maximum plasma concentration of drug at injection site will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole | Day 1 to Day 182/Early Termination | 
| Pharmacokinetics - time of maximum plasma concentration (tmax) | The amount of time that the maximum plasma concentration of drug at injection site will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole | Day 1 to Day 182/Early Termination | 
| Pharmacokinetics - area under concentration-time curve (AUC) calculated from time zero to time t (AUCt) | AUCt will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole to determine average concentration of drug over time | Day 1 to Day 182/Early Termination | 
| Pharmacokinetics - AUC calculated from time to infinity | AUCinfinity will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole to determine total drug exposure over time | Day 1 to Day 182/Early Termination | 
| Pharmacokinetics - Terminal-phase elimination half-life (t1/2,z) | t1/2,z will be assessed for plasma Aripiprazole and its major metabolite dehydro-aripiprazole to determine drug persistence in the body | Day 1 to Day 182/Early Termination |