Study in Stabilized Schizophrenic Patients to Evaluate the Pharmacokinetics of Risperidone and 9-Hydroxy (OH)-Risperidone When Risperidone is Administered From a Polyurethane Implant

Study Overview
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Brief Summary
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The study will be a 6-month, open-label, multiple center study in approximately 50 stable subjects diagnosed with schizophrenia or schizoaffective disorder to evaluate the safety, tolerability, and pharmacokinetics of Risperidone and 9-OH-Risperidone following implantation of two or three, 300 mg Risperidone Implants.

Detailed Description
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The study will be a 6-month, open-label, study in approximately 50 stable subjects diagnosed with schizophrenia or schizoaffective disorder to evaluate the safety, tolerability, and pharmacokinetics of Risperidone and 9-OH-Risperidone following implantation of two or three, 300 mg Risperidone Implants. Subjects who are diagnosed with schizophrenia or schizoaffective disorder according to DSM-V and are stable on a daily 4 mg oral dose of Risperidone for at least 8 weeks will be recruited into the study. Subjects stable on a 4 mg oral dose of Risperidone will be implanted with two or three, 300 mg, Risperidone Implants. All implants will be placed in the inner aspect of the upper arm. Plasma concentrations of Risperidone and the active moiety will be measured prior to placement of the Risperidone Implants, throughout the implantation period, and after re-converting to oral Risperidone following the removal of the Risperidone Implants.

Official Title
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Study in Stabilized Schizophrenic Patients to Evaluate the Pharmacokinetics of Risperidone and 9-Hydroxy (OH)-Risperidone When Risperidone is Administered From a Polyurethane Implant

Conditions
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Schizophrenia, Schizo-affective Disorder

Intervention / Treatment
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* Drug: Risperidone Implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject (and/or a subject's authorized legal representative) has provided written informed consent Patient meets the following criteria: Outpatient status PANSS Total Score ≤ 80 at screening and if PANSS score at baseline is ≥ 20% change from screening, the patients cannot participate in the study. A score of ≤ 3 on the following PANSS items: Conceptual disorganization Suspiciousness Hallucinatory behavior Unusual thought content Subject is male or female between 18 to 60 years of age Subject has a diagnosis of schizophrenia or schizoaffective disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria Exclusion Criteria: Hospitalized or required acute crisis intervention for symptom exacerbation in the 60 days prior to admission as determined by the Investigator Subject has a history of suicide attempt in the last year, or in the opinion of the investigator is currently at imminent risk of suicide Has a current or recent (within 12 months) DSM-V diagnosis of moderate or severe substance use disorder (except for tobacco use disorder) or has a positive urine drug screen for prohibited substances at screening. Have impaired hepatic (ALT/AST >1.5 times higher than the upper limit of normal) or renal function (eGFR<50 mL/min) Previously defined hypersensitivity to Risperidone History of neuromalignant syndrome (NMS) Electroconvulsive therapy within 6 months of admission Requires current use of agents that are strong inhibitors and inducers of cytochrome P450 2D6

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 600 mg<br>Two, 300 mg Risperidone Implants | Drug: Risperidone Implant<br> <br> |
| Experimental: 900 mg<br>Three, 300 mg Risperidone Implants | Drug: Risperidone Implant<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) for Active Moiety, 9-hydroxy-risperidone and Risperidone |  | 6 months | 
| Cmax for Active Moiety, 9-hydroxy-risperidone and Risperidone |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Efficacy of a Risperidone Implant as Assessed by the Positive and Negative Syndrome Scale (PANSS) |  | 12 months |