A Study to Test if TV-46000 is Safe for Maintenance Treatment of Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: TV-46000; Placebo
Intervention description: TV-46000 will be administered per dose and schedule specified in the arm description.; Placebo matching to TV-46000 will be administered per schedule specified in the arm description.
Intervention MeSH terms: Risperidone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 336.0
Sex: All
Minimum age: 13 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to evaluate the long-term safety and tolerability of
      TV-46000. The primary safety and tolerability endpoint is the frequency of all adverse
      events, including serious adverse events. For new participants, the total duration of
      participant participation in the study is planned to be up to 80 weeks (including a screening
      period of up to 4 weeks, a 12-week oral conversion/stabilization stage [Stage 1], a 56-week
      double-blind maintenance stage [Stage 2], and a follow-up period [8 weeks]). For roll-over
      participants, the total duration of participant participation in the study is planned to be
      up to 64 weeks (including up to 56 weeks in the maintenance stage [Stage 2] and a follow-up
      period [8 weeks]). Participants who started Stage 2 who relapse or meet 1 or more of the
      withdrawal criteria should be invited to perform the Early Termination visit as soon as
      possible within 4 weeks of the last injection. Participants who withdraw from the study
      before completing the 56-week maintenance stage will have follow-up procedures and
      assessments performed at their follow-up visits. During the follow-up period, participants
      will be treated according to the investigator's judgment.

      All participants will be treated with active drug.
    

Eligibility criteria:

        Inclusion Criteria:

        Participants Rolling Over from the Pivotal Efficacy Study TV46000-CNS-30072:

          -  The participant must have participated in the pivotal efficacy study (Study
             TV46000-CNS-30072) without experiencing relapse events and without important protocol
             deviations.

          -  If the participant was taking antidepressants or mood stabilizers in Study
             TV46000-CNS-30072, no dose changes or initiation of treatment with these medications
             will be permitted.

          -  The participant, in the investigator's judgment, requires chronic treatment with an
             antipsychotic medication.

          -  The participant is able to understand the nature of the study and follow protocol
             requirements, including the prescribed dosage regimens (oral and SC administration)
             and non-use of prohibited concomitant medications; can read and understand the written
             word in order to complete participant-reported outcomes measures; and can be reliably
             rated on assessment scales.

          -  The participant has had a stable place of residence for the previous 3 months before
             the baseline visit in this study, and changes in residence are not anticipated over
             the course of study participation.

          -  The participant has no significant life events (such as pending loss of housing,
             family status change, long travel abroad, surgery, etc) that could affect study
             outcomes expected throughout the period of study participation.

          -  Women of childbearing potential and sexually active female adolescents must agree not
             to try to become pregnant, and, unless they have exclusively same-sex partners, must
             agree to use a highly effective method of contraception and agree to continue use of
             this method beginning 1 month before the first administration of study drug and for
             the duration of the study and for 120 days after the last injection of study drug.

          -  The participant, if adult or adolescent male, is surgically sterile, or, if capable of
             producing offspring, has exclusively same-sex partners or is currently using an
             approved method of birth control and agrees to the continued use of this method for
             the duration of the study (and for 120 days after the last dose of study drug). Male
             participants with sex partners who are women of childbearing potential must use
             condoms even if surgically sterile. In addition, male participants may not donate
             sperm for the duration of the study and for 120 days after taking the study drug.

        New Participants (Not Rolling Over from the Pivotal Efficacy Study TV46000-CNS-30072):

          -  The participant has a diagnosis of schizophrenia

          -  The participant has been responsive to an antipsychotic treatment (other than
             clozapine) in the past year based on investigator judgment (and discussions with
             family members, caregivers, or healthcare professionals as applicable).

          -  The participant, in the investigator's judgment, requires chronic treatment with an
             antipsychotic medication.

          -  The participant is able to understand the nature of the study and follow protocol
             requirements, including the prescribed dosage regimens (oral and sc administration)
             and non-use of prohibited concomitant medications; can read and understand the written
             word in order to complete participant-reported outcomes measures; and can be reliably
             rated on assessment scales.

          -  The participant has had a stable place of residence for the previous 3 months before
             screening, and changes in residence are not anticipated over the course of study
             participation.

          -  The participant has no significant life events (such as pending loss of housing,
             family status change, long travel abroad, surgery, etc) that could affect study
             outcomes expected throughout the period of study participation.

          -  The participant has a body mass index between 18.0 and 38.0 kilograms (kg)/square
             meter (m^2), inclusive.

          -  Women of childbearing potential and sexually active female adolescents must agree not
             to try to become pregnant, and, unless they have exclusively same-sex partners, must
             agree to use a highly effective method of contraception and agree to continue use of
             this method beginning 1 month before the first administration of study drug and for
             the duration of the study and for 120 days after the last injection of study drug.

          -  The participant, if adult or adolescent male, is surgically sterile, or, if capable of
             producing offspring, has exclusively same-sex partners or is currently using an
             approved method of birth control and agrees to the continued use of this method for
             the duration of the study (and for 120 days after the last dose of study drug). Male
             participants with sex partners who are women of childbearing potential must use
             condoms even if surgically sterile. In addition, male participants may not donate
             sperm for the duration of the study and for 120 days after taking the study drug.

          -  Additional criteria apply, please contact the investigator for more information.

        Exclusion Criteria:

        Participants Rolling Over from the Pivotal Efficacy Study TV46000-CNS-30072:

          -  The participant has a finding in the baseline 12-lead electrocardiogram (ECG) that is
             considered clinically significant in the judgment of the investigator.

          -  Poor compliance with study procedures (in the opinion of the investigator or sponsor)
             during the pivotal efficacy Study TV46000-CNS-30072. This should be discussed on a
             case-by-case basis.

        New Participants (Not Rolling Over from the Pivotal Efficacy Study TV46000-CNS-30072) and
        Roll-Over Participants:

          -  The participant is currently on clozapine or has received electroconvulsive therapy in
             the last 12 months.

          -  The participant has a history of epilepsy or seizures, neuroleptic malignant syndrome,
             tardive dyskinesia, or other medical condition that would expose the participant to
             undue risk.

          -  The participant has a positive serology for human immunodeficiency virus (HIV)-1,
             HIV-2, hepatitis B surface antigen, and/or hepatitis C.

          -  The participant has current or a history of known hypersensitivity to risperidone or
             any of the excipients of TV-46000 or the oral formulation of risperidone used in the
             stabilization phase.

          -  The participant has a substance use disorder, including alcohol and benzodiazepines
             but excluding nicotine and caffeine.

          -  The participant is a pregnant or lactating female.

          -  The participant has used an investigational drug other than TV-46000 within 3 months
             prior to screening or has participated in a non-drug clinical trial within 30 days
             prior to screening.

          -  Vulnerable participants (for example, people kept in detention).

          -  Additional criteria apply, please contact the investigator for more information.