Study to Evaluate the Efficacy and Safety of Risperidone ISM® in Patients With Acute Schizophrenia: Open Label Extension
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Risperidone ISM 75 mg; Risperidone ISM 100 mg
Intervention description: Monthly (once every 4 weeks) intramuscular (IM) injection in the gluteal or deltoid muscle.; Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
Intervention MeSH terms: Risperidone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: It is an open label extension
Enrollment: 215.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This is the long-term open label extension (OLE) of the study PRISMA-3 (NCT03160521). Those
      patients who complete participation in the main segment of the study (double blind) together
      with other clinically stable not previously enrolled (de novo patients) may opt to
      participate in this extension segment, where they will receive active Risperidone ISM® (75 mg
      or 100 mg)under open-label conditions every four weeks for approximately 12 months.
    

Eligibility criteria:

        Participation in the open-label extension segment of the study PRISMA-3 is optional, and
        patients who complete participation in the main segment of the study (double blind segment
        of PRISMA-3, NCT03160521) may opt to not participate. Patients who are interested in
        participating must meet all eligibility criteria in order to enter into the extension
        segment.

        Inclusion Criteria (Rollover patients):

        To be eligible for entry into the extension segment of the study PRISMA-3, a patient must
        meet all of the following criteria at the extension baseline time point (immediately upon
        completion of the end-of-treatment visit assessments and procedures for the main part of
        the study):

          1. Has completed scheduled participation in the double blind segment of the study
             PRISMA-3, through to the end of the treatment period and including the
             end-of-treatment visit

          2. Continues to require long-term treatment with an antipsychotic medication, in the
             opinion of the investigator

          3. Continues to meet contraceptive requirements of the study PRISMA-3

          4. Is willing to participate in the extension segment of the study and remains capable of
             providing informed consent

             a. A signed informed consent form must be provided before any study assessments are
             performed for the extension segment

          5. Continues to reside in a stable living situation, in the opinion of the investigator

          6. Continues to have an identified reliable informant, in the opinion of the investigator

        Exclusion Criteria (Rollover patients):

        An individual who meets any of the following criteria at the extension baseline time point
        (immediately upon completion of the end-of-treatment visit assessments and procedures for
        the double blind segment PRISMA-3) will not be permitted to enter into this extension
        segment of the study PRISMA-3:

          1. Missed more than 1 scheduled study visit during participation in the double blind
             segment of study PRISMA-3

          2. Had an abnormal clinical laboratory value, vital sign, or ECG finding during
             participation in the main part of the study that, in the opinion of the investigator,
             was clinically relevant, related to study drug, and would compromise the well-being of
             the patient in the extension segment

          3. Had a clinically significant or unstable medical illness/condition/disorder during the
             main part of the study that would be anticipated, in the investigator's opinion, to
             potentially compromise patient safety in the extension segment

          4. Is taking or is anticipated to require any prohibited concomitant medication

          5. Pregnant, lactating, or breastfeeding

          6. Any contraindication for continued IM injections (e.g., treatment with anticoagulant)

          7. Inadequate gluteal or deltoid musculature or excessive fat, as determined by the
             investigator, that would interfere with IM study drug injections

          8. Study site personnel and/or persons employed by the investigator or study site or is
             an immediate family member of such persons

        Inclusion Criteria (De Novo Patients):

          1. Capable of providing informed consent

          2. Age ≥ 18 and ≤ 65 years old

          3. On a stable dose of oral risperidone from 4 to 6 mg daily as maintenance therapy for
             at least the last 4 weeks prior/before screening/baseline and would potentially
             benefit from conversion to an extended release injectable, in the opinion of the
             investigator

          4. Current diagnosis of schizophrenia, according to the Diagnostic and Statistical Manual
             of Mental Disorders, Fifth Edition (DSM-5) criteria that is clinically stable as
             evidenced by:

               -  No hospitalizations for acute exacerbations of schizophrenia and psychiatrically
                  stable without significant symptom exacerbation over the last 3 months before
                  screening based on the investigator's judgment

               -  PANSS total score < 70 at screening

               -  CGI-S score of ≤ 3 (mild) at screening

          5. Has previously had a clinically significant beneficial response (improvement in
             schizophrenia symptoms), as determined by the investigator, to treatment with an
             antipsychotic medication other than clozapine

          6. At least 2 years elapsed since initial onset of active-phase schizophrenia symptoms

          7. Subject is outpatient; not hospitalized for worsening of schizophrenia within the last
             3 months (hospitalization for social management within this time period is acceptable)

          8. Medically stable over the last month prior to screening based on the investigator's
             judgment

          9. BMI of 18.5 to 40.0 kg/m2 (inclusive) at screening

         10. Agrees to discontinue prohibited medications as applicable and as clinically indicated
             according to investigator instructions

         11. Dosages of all permitted medications are considered to have been stable (with the
             exception of medication to be used on an as-needed basis) for ≥ 2 weeks prior to the
             baseline visit and to remain stable during participation in this study

         12. Resides in a stable living situation, in the opinion of the investigator

         13. Has an identified reliable informant, in the opinion of the investigator

         14. Meets the contraceptive criteria stablished in the study

         15. Agrees not to post any personal medical data related to the study or information
             related to the study on any website or social media site during the study duration.

        Exclusion Criteria (De Novo Patients):

          1. History of proven inadequate clinical response to treatment with therapeutic doses
             (with good compliance) of risperidone or paliperidone

          2. History of treatment resistance, defined as failure to respond to 2 discrete adequate
             trials (≥ 4 weeks with an adequate dose) of 2 different antipsychotic medications;
             history of clozapine use (exception: use was not because of treatment resistance or
             refractory psychotic symptoms)

          3. Known or suspected intolerance of or allergy or hypersensitivity to risperidone,
             paliperidone, or any of the excipients in the IM formulations of these

          4. History of neuroleptic malignant syndrome, clinically significant tardive dyskinesia
             or tardive dystonia

          5. History of any other medical condition that is considered to pose any unjustifiable
             risk or interfere with study assessments

          6. Clinically significant extrapyramidal symptoms at screening or baseline

          7. At significant risk of suicidal, homicidal or violent ideation or behavior, by history
             or as clinically assessed by the investigator at screening visit

          8. Answer of "yes" on item 4 or on item 5 of the Columbia-Suicide Severity Rating Scale
             (C-SSRS) (ideation) with the most recent episode occurring within the past 2 months,
             or answer "yes" to any of the 5 items (behavior) with an episode occurring within the
             last year

          9. Current diagnosis or a history of substance use disorder according to DSM-5 criteria
             within 6 months prior to the screening visit (with the exception of tobacco, mild
             cannabis, or mild alcohol use disorder) or a positive drug screen test (with the
             exception of cannabis) verified by repeat testing

         10. Lifetime history of diagnosis of schizoaffective disorder or bipolar disorder

         11. Clinically significant comorbid neuropsychiatric disorders

         12. Clinically significant or unstable medical illness/condition/disorder that would be
             anticipated, in the investigator's opinion, to potentially compromise patient safety
             or adversely affect the evaluation of efficacy

         13. Laboratory abnormality that, in the opinion of the investigator, would compromise the
             well-being of the patient, or any of the following laboratory abnormalities at
             screening or baseline

         14. Pregnant, lactating, or breastfeeding

         15. Inadequate gluteal or deltoid musculature or excessive fat, as determined by the
             investigator, that would interfere with IM study drug injections

         16. Any contraindication for IM injections

         17. Receipt of any long-acting antipsychotic medication by IM injection within 60 days
             before screening

         18. Current involuntary hospitalization or incarceration

         19. Hospitalized for more than 30 days during the 90 days before screening

         20. Participation in another clinical study in which the patient received an experimental
             or investigational drug or agent within 6 months before screening

         21. Participation in a clinical study with Risperidone ISM within 12 months before
             screening

         22. Study site personnel and/or persons employed by the investigator or study site or is
             an immediate family member of such persons

         23. Patients taking or anticipated to require any prohibited concomitant medication