Study to Evaluate TV-46000 as Maintenance Treatment in Adult and Adolescent Participants With Schizophrenia

NCT ID: NCT03503318

Last Updated: 2023-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 544 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-27
• Study Completion Date: 2020-12-03

Brief Summary

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

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Participants will receive an SC injection of placebo matching to TV-46000 at baseline and every 4 weeks (q4w) thereafter. Participants will continue treatment until they experience a relapse event; meet 1 or more of the study discontinuation or withdrawal criteria; or remain relapse-free during the double-blind phase until the study is terminated.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching to TV-46000 will be administered per schedule specified in the arm.

TV-46000 q1m

Participants will receive an SC injection of TV-46000 at baseline and q4w thereafter. The maximal dose for adult participants is comparable to an oral risperidone dose of 5 milligrams (mg)/day, and the maximal dose for adolescents is comparable to 4 mg/day. Participants will continue treatment until they experience a relapse event; meet 1 or more of the study discontinuation or withdrawal criteria; or remain relapse-free during the double-blind phase until the study is terminated.

Group Type: EXPERIMENTAL

TV-46000

Intervention Type: DRUG

TV-46000 will be administered per dose and schedule specified in the arm.

TV-46000 q2m

Participants will receive an SC injection of TV-46000 at baseline and every 8 weeks (q8w) thereafter, and a placebo SC injection 4 weeks after baseline and q8w thereafter. The maximal dose for adult participants is comparable to an oral risperidone dose of 5 mg/day, and the maximal dose for adolescents is comparable to 4 mg/day. Participants will continue treatment until they experience a relapse event; meet 1 or more of the study discontinuation or withdrawal criteria; or remain relapse-free during the double-blind phase until the study is terminated.

Group Type: EXPERIMENTAL

TV-46000

Intervention Type: DRUG

TV-46000 will be administered per dose and schedule specified in the arm.

Placebo

Intervention Type: DRUG

Placebo matching to TV-46000 will be administered per schedule specified in the arm.

Interventions

TV-46000

TV-46000 will be administered per dose and schedule specified in the arm.

Intervention Type: DRUG

Placebo

Placebo matching to TV-46000 will be administered per schedule specified in the arm.

Intervention Type: DRUG

Other Intervention Names

Risperidone

Eligibility Criteria

Inclusion Criteria

• The participant has a diagnosis of schizophrenia for >1 year and has had ≥1 episode of relapse in the last 24 months.
• The participant has been responsive to an antipsychotic treatment (other than clozapine) in the past year based on discussions with family members or healthcare professionals.
• The participant 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 participant 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 participant, 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 participants 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 participant 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 participant is currently on clozapine or 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 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 has previously participated in a Teva-sponsored clinical study with TV-46000.
• The participant is a pregnant or lactating female.
• The participant has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
• The participant 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

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teva Medical Expert, MD

Role: STUDY_DIRECTOR

Teva Branded Pharmaceutical Products R&D, Inc.

Locations

Teva Investigational Site 14769

Little Rock, Arkansas, United States

Teva Investigational Site 14796

Rogers, Arkansas, United States

Teva Investigational Site 14811

Anaheim, California, United States

Teva Investigational Site 14794

Bellflower, California, United States

Teva Investigational Site 14776

Colton, California, United States

Teva Investigational Site 14767

Costa Mesa, California, United States

Teva Investigational Site 14802

Costa Mesa, California, United States

Teva Investigational Site 14773

Culver City, California, United States

Teva Investigational Site 14835

Garden Grove, California, United States

Teva Investigational Site 14774

Glendale, California, United States

Teva Investigational Site 14817

La Habra, California, United States

Teva Investigational Site 14771

Lemon Grove, California, United States

Teva Investigational Site 14823

Long Beach, California, United States

Teva Investigational Site 14816

Montclair, California, United States

Teva Investigational Site 14803

Norwalk, California, United States

Teva Investigational Site 14786

Oakland, California, United States

Teva Investigational Site 14797

Oceanside, California, United States

Teva Investigational Site 14827

Oceanside, California, United States

Teva Investigational Site 14777

Orange, California, United States

Teva Investigational Site 14815

Pico Rivera, California, United States

Teva Investigational Site 14812

Riverside, California, United States

Teva Investigational Site 14785

San Bernardino, California, United States

Teva Investigational Site 14818

San Diego, California, United States

Teva Investigational Site 14828

San Diego, California, United States

Teva Investigational Site 14819

San Marcos, California, United States

Teva Investigational Site 14779

Santa Ana, California, United States

Teva Investigational Site 14788

Torrance, California, United States

Teva Investigational Site 14768

Coral Gables, Florida, United States

Teva Investigational Site 14783

Coral Gables, Florida, United States

Teva Investigational Site 14836

Hallandale, Florida, United States

Teva Investigational Site 14787

Hialeah, Florida, United States

Teva Investigational Site 14814

Hialeah, Florida, United States

Teva Investigational Site 14799

Lauderhill, Florida, United States

Teva Investigational Site 14832

Miami, Florida, United States

Teva Investigational Site 14810

North Miami, Florida, United States

Teva Investigational Site 14831

Orange City, Florida, United States

Teva Investigational Site 14806

Orlando, Florida, United States

Teva Investigational Site 14837

Tampa, Florida, United States

Teva Investigational Site 14824

Atlanta, Georgia, United States

Teva Investigational Site 14834

Columbus, Georgia, United States

Teva Investigational Site 14821

Decatur, Georgia, United States

Teva Investigational Site 14770

Marietta, Georgia, United States

Teva Investigational Site 14765

Chicago, Illinois, United States

Teva Investigational Site 14829

Chicago, Illinois, United States

Teva Investigational Site 14805

Hoffman Estates, Illinois, United States

Teva Investigational Site 14825

Shreveport, Louisiana, United States

Teva Investigational Site 14764

Glen Burnie, Maryland, United States

Teva Investigational Site 14820

New Bedford, Massachusetts, United States

Teva Investigational Site 14798

Saginaw, Michigan, United States

Teva Investigational Site 14791

St Louis, Missouri, United States

Teva Investigational Site 14813

St Louis, Missouri, United States

Teva Investigational Site 14826

St Louis, Missouri, United States

Teva Investigational Site 14790

St Louis, Missouri, United States

Teva Investigational Site 14809

Las Vegas, Nevada, United States

Teva Investigational Site 14792

Berlin, New Jersey, United States

Teva Investigational Site 14830

Princeton, New Jersey, United States

Teva Investigational Site 14772

Cedarhurst, New York, United States

Teva Investigational Site 14804

New York, New York, United States

Teva Investigational Site 14800

New York, New York, United States

Teva Investigational Site 14784

New York, New York, United States

Teva Investigational Site 14780

Staten Island, New York, United States

Teva Investigational Site 14763

Cincinnati, Ohio, United States

Teva Investigational Site 14782

Dayton, Ohio, United States

Teva Investigational Site 14822

Oklahoma City, Oklahoma, United States

Teva Investigational Site 14789

Allentown, Pennsylvania, United States

Teva Investigational Site 14833

Norristown, Pennsylvania, United States

Teva Investigational Site 14775

Scranton, Pennsylvania, United States

Teva Investigational Site 14793

Thorndale, Pennsylvania, United States

Teva Investigational Site 14778

Charleston, South Carolina, United States

Teva Investigational Site 14781

Dallas, Texas, United States

Teva Investigational Site 14766

Dallas, Texas, United States

Teva Investigational Site 14801

Houston, Texas, United States

Teva Investigational Site 14807

Irving, Texas, United States

Teva Investigational Site 59148

Burgas, , Bulgaria

Teva Investigational Site 59152

Kazanlak, , Bulgaria

Teva Investigational Site 59151

Lovech, , Bulgaria

Teva Investigational Site 59149

Novi Iskar, , Bulgaria

Teva Investigational Site 59144

Sofia, , Bulgaria

Teva Investigational Site 59154

Varna, , Bulgaria

Teva Investigational Site 59150

Varna, , Bulgaria

Teva Investigational Site 59146

Vratsa, , Bulgaria

Countries

United States; Bulgaria

References

Correll CU, Knebel H, Harary E, Eshet R, Tohami O, Suett M, Sharon N, Franzenburg KR, Kane JM. Safety Outcomes with the Long-Acting Subcutaneous Antipsychotic TV-46000 in Schizophrenia: A Post Hoc Analysis of Behavioral, Neuromotor, Endocrine, and Cardiometabolic Outcomes from Two Phase 3 Studies. CNS Drugs. 2025 Jul 29. doi: 10.1007/s40263-025-01197-1. Online ahead of print.

Reference Type: DERIVED

PMID: 40730715 (View on PubMed)

Kane JM, Harary E, Eshet R, Tohami O, Weiser M, Leucht S, Merenlender-Wagner A, Sharon N, Davis GL 3rd, Suett M, Franzenburg KR, Correll CU. Efficacy and safety of TV-46000, a long-acting, subcutaneous, injectable formulation of risperidone, for schizophrenia: a randomised clinical trial in the USA and Bulgaria. Lancet Psychiatry. 2023 Dec;10(12):934-943. doi: 10.1016/S2215-0366(23)00288-2. Epub 2023 Nov 2.

Reference Type: DERIVED

PMID: 37924833 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001619-65

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TV46000-CNS-30072

Identifier Type: -

Identifier Source: org_study_id