Safety, Tolerability, Pharmacokinetics and Efficacy of 180 mg Subcutaneous Risperidone From 6 mg Oral Risperidone
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: PERSERIS; Risperidone
Intervention description: PERSERIS is an extended-release SC injectable suspension administered once-monthly; Oral risperidone
Intervention MeSH terms: Risperidone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: The study will enroll subjects currently on a stable dose of 5 or 6 mg of oral risperidone. After screening, eligible subjects will be admitted to the clinical unit and stabilized on 6 mg daily (3 mg oral risperidone twice a day) for 5 days, followed by an additional 3 days, during which the first injection of PERSERIS will be administered. Subjects will then return to the clinical unit every 28 days for an additional 3 admit periods for subsequent PERSERIS injections (2 injections per visit).
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study evaluates PERSERIS at a higher dose than what has been administered in previous
      clinical trials. Subjects with stable schizophrenia on a dose of 5-6 mg oral risperidone will
      be switched to PERSERIS at the higher dose, which is believed to be similar to the oral dose
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of schizophrenia

          -  Clinically stable as defined as no hospitalizations for acute exacerbations within 3
             months of screening and Screening PANSS score ≤70

          -  Total body mass index (BMI) between 18 and 35 kg/m2

          -  Given written informed consent

        Exclusion Criteria:

          -  Received a once-monthly long-acting injectable (LAI) antipsychotic within 60 days of
             screening and a once every 3 month LAI antipsychotic within 120 days of screening

          -  Taking the following concurrent or over the counter (OTC) products:

               1. Inducers or inhibitors of CYP2D6 within 14 days or 5 half-lives whichever is
                  greater prior to study screening

               2. Bupropion, chlorpheniramine, cimetidine, clomipramine, doxepin or quinidine
                  within 30 days prior to study screening

               3. Clozapine, phenothiazines, aripiprazole, haloperidol or any other antipsychotic
                  other than oral risperidone within 14 days prior to study screening

               4. Selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine
                  reuptake inhibitors (SNRIs) within 30 days prior to study screening

               5. Opioids or opioid-containing analgesics within 14 days prior to study screening

               6. Medications, in the addition to those listed above which in the opinion of the
                  Investigator in conjunction with the medical monitor, may be expected to
                  significantly interfere with the metabolism or excretion of risperidone and/or
                  9-hydroxyrisperidone, that may be associated with a significant drug interaction
                  with risperidone, or that may pose a significant risk to subjects' participation
                  in the study. The medical monitor should be contacted with any questions
                  regarding the use of CYP2D6 or 3A4 inducers or inhibitors in particular.

          -  History of cancer (with the exception of resected basal cell or squamous cell
             carcinoma of the skin) unless they have been disease free for ≥5 years.

          -  Another active medical condition or organ disease that may either compromise subject
             safety or interfere with the safety and/or outcome evaluation of the study drug.

          -  Evidence or history of a significant hepatic disorder that may either compromise
             subject safety or interfere with the safety and/or outcome evaluation of the study
             drug. Individuals with acute or chronic hepatitis (including but not limited to
             hepatitis B or C); or individuals with 1) total bilirubin >1.5x the upper limit of
             normal (ULN) and/or 2) alanine aminotransferase (ALT) or aspartate aminotransferase
             (AST) >3x ULN will be excluded.

          -  A history of renal disease, or a creatinine clearance of less than 60 mL/min (as
             determined by the Cockcroft-Gault formula).

          -  A history of orthostatic hypotension, syncope, significant low white blood cell (WBC)
             count (i.e., based on absolute neutrophil count or drug-induced leukopenia or other
             medical conditions including, but not limited to, history of heart attack (i.e.,
             myocardial infarction) or brain injury (i.e., traumatic with loss of consciousness
             and/or cardiovascular accident) within a year of Screening and clinically significant
             low blood pressure or arrhythmias as interpreted by the principal investigator (PI).

          -  Corrected QT interval [Fridericia's calculation (QTcF)] >450 msec (male) or >470 msec
             (female) at screening or prior to administration of the 1st dose of PERSERIS, or with
             a known history of Torsades de Points, or family member with sudden unexplained
             cardiac death.

          -  Known to have AIDS (acquired immunodeficiency syndrome) or to be HIV (human
             immunodeficiency virus) positive.

          -  Suicidal ideation with intent and plan, as assessed by affirmative answers to C-SSRS
             questions 4 and 5 of the ideation section,or suicide attempts within the last 6 months
             as noted on the C-SSRS, or subjects with uncontrolled depression in the opinion of the
             Investigator.

          -  Known diagnosis of type 1 diabetes or subjects with Haemoglobin A1c (HbA1c) >8.0% at
             screening.

          -  Participated in a clinical trial within 30 days prior to study screening.

          -  Significant traumatic injury, major surgery or open biopsy within 30 days prior to
             study screening.

          -  Meet the criteria for the diagnosis of current moderate or severe substance use
             disorder.

          -  Prior allergic reactions, sensitivities, or other known contraindications to any
             component of PERSERIS.

          -  Women of childbearing potential who are pregnant or breastfeeding, seeking pregnancy
             or failing to use adequate contraceptive methods during the study.

          -  Positive urine drug screen (UDS) anytime through Day -1 for opioids, cocaine,
             amphetamines, methadone, cannabinoids, barbiturates, benzodiazepines, methamphetamine
             and phencyclidine, unless the positive screen is determined to be secondary to an
             allowable concomitant medication. If a positive UDS is possibly the result of a
             subject's use of OTC or prescription medications, a repeat urine drug screen may be
             permissible. Study site personnel should contact the medical monitor for approval to
             retest.

          -  Tardive dyskinesia as assessed by a score of ≥2 on Item 8 of the Abnormal Involuntary
             Movement Scale (AIMS) at Screening.

          -  Epilepsy or other seizure disorders, Parkinson's disease or dementia.

          -  History of neuroleptic malignant syndrome.

          -  Previously injected with PERSERIS within 6 months prior to screening.

          -  Unable, in the opinion of the PI, to comply fully with the study requirements.

          -  Determined to be poor metabolisers, intermediate metabolisers or ultra-rapid
             metabolisers for CYP2D6 genotype.