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Evaluate TV-46000 as Maintenance Treatment in Adult and Adolescent Patients With Schizophrenia (RISE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03503318
Recruitment Status : Active, not recruiting
First Posted : April 19, 2018
Last Update Posted : July 1, 2020
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )

Brief Summary:
The purpose of the study is to evaluate the efficacy, safety, and tolerability of different dose regimens of TV-46000 administered subcutaneously as compared to placebo during maintenance treatment in adult and adolescent patients with schizophrenia. The study will include male and female patients, 13 to 65 years of age, who have a confirmed diagnosis of schizophrenia, are clinically stable, and are eligible for risperidone treatment.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: TV-46000 - A Drug: TV-46000 - B Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 863 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Risperidone Extended-Release Injectable Suspension (TV-46000) for Subcutaneous Use as Maintenance Treatment in Adult and Adolescent Patients With Schizophrenia
Actual Study Start Date : April 27, 2018
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : October 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Risperidone

Arm Intervention/treatment
Experimental: TV-46000 - A
Dose regimen A
Drug: TV-46000 - A
Subcutaneous injections
Other Name: Risperidone

Experimental: TV-46000 - B
Dose regimen B
Drug: TV-46000 - B
Subcutaneous injections
Other Name: Risperidone

Placebo Comparator: Placebo
Matching Placebo
Drug: Placebo
Subcutaneous injections

Primary Outcome Measures :
  1. Time to Impending Relapse [ Time Frame: 15 months ]
    Will be calculated as the earliest date the patient meets ≥1 of the impending relapse criteria

Secondary Outcome Measures :
  1. Time to impending relapse [ Time Frame: 15 months ]
    As defined under the primary objective in the total population (adults and adolescents).

  2. Time to impending relapse in adolescent patients with schizophrenia [ Time Frame: 15 months ]
    This assessment is pending randomization of at least 10 adolescent patients with clinically sufficient exposure.

  3. Impending Relapse Rate [ Time Frame: Week 24 ]
    This rate will be estimated using the Kaplan-Meier method.

  4. Observed Rate of Impending Relapse [ Time Frame: 15 months ]
    Calculated as the number of patients who relapsed by endpoint divided by the number of patients in each treatment group.

  5. Percentage of Patients Who Maintain Stability [ Time Frame: 15 months ]
    Stability is defined as meeting all of the following criteria for at least 4 consecutive weeks: outpatient status; PANSS total score ≤80; minimal presence of specific psychotic symptoms on the PANSS, as measured by a score of ≤4 on each of the following items: conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content; Clinical Global Impression of Severity (CGI-S) score ≤4 (moderately ill); and Clinical Global Impression-Severity of Suicidality (CGI-SS) score ≤2 (mildly suicidal) on Part 1 and ≤5 (minimally worsened) on Part 2. The percentage will be calculated as the number of patients who maintained stability at endpoint divided by the number of patients in the given treatment group.

  6. Percentage of Patients Achieving Remission [ Time Frame: 15 months ]
    Positive symptom, negative symptom, and overall symptom remission will be examined and are defined by Andreasen et al (2005), including severity and duration criteria. All remission criteria can be derived from PANSS items.

  7. Percentage of Participants with Adverse Events [ Time Frame: 15 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   13 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • The patient has a diagnosis of schizophrenia for >1 year and has had ≥1 episode of relapse in the last 24 months.
  • The patient has been responsive to an antipsychotic treatment (other than clozapine) in the past year based on discussions with family members or healthcare professionals.
  • The patient has 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 patient has no significant life events 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 drugs and for the duration of the study and for 120 days after the last injection of study drug.
  • The patient, if adult or adolescent male, is surgically sterile, or, if capable of producing offspring, or 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 patients with sex partners who are women of childbearing potential must use condoms even if surgically sterile

    • Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

  • The patient has a current clinically significant Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, or amnestic or other cognitive disorders, or borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
  • The patient is currently on clozapine or received electroconvulsive therapy in the last 12 months.
  • The patient has a history of epilepsy or seizures, neuroleptic malignant syndrome, tardive dyskinesia, or other medical condition that would expose the patient to undue risk.
  • The patient has a positive serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B surface antigen, and/or hepatitis C.
  • The patient has current or 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 patient has a substance use disorder, including alcohol and benzodiazepines but excluding nicotine and caffeine.
  • The patient has previously participated in a Teva-sponsored clinical study with TV-46000.
  • The patient is a pregnant or lactating female.
  • The patient has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
  • The patient has used an investigational drug within 3 months prior to screening or has participated in a non-drug clinical trial within 30 days prior to screening.

    • Additional criteria apply, please contact the investigator for more information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03503318

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Sponsors and Collaborators
Teva Branded Pharmaceutical Products R&D, Inc.
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Study Director: Teva Medical Expert, MD Teva Pharmaceuticals USA
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Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc. Identifier: NCT03503318    
Other Study ID Numbers: TV46000-CNS-30072
03503318 ( Registry Identifier: )
2018-001619-65 ( EudraCT Number )
First Posted: April 19, 2018    Key Record Dates
Last Update Posted: July 1, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents