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

NCT03503318 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: TV46000-CNS-300722018-001619-65
• Study Type: interventional
• Target: 544
• Locations: 2 countries
• Sites: 81

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

Outcome Measures

Primary Outcomes (1)

• Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set

  Relapse was defined as 1 or more of the following items: • Clinical Global Impression-Improvement (CGI-I) of ≥5, and - an increase of any of the 4 Positive and Negative Syndrome Scale (PANSS) items: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content, to a score of \>4 with an absolute increase of ≥2 on specific item since randomization, or - an increase in any of the 4 individual PANSS items to a score of \>4 and an absolute increase of ≥4 on combined score of 4 items since randomization; • hospitalization due to worsening of psychotic symptoms; • Clinical Global Impression-Severity of Suicidality (CGI-SS) of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2; • violent behavior resulting in clinically significant self-injury, injury to another person, or property damage. Data is presented as distribution of relapsing participants (number of participants with impending relapse).

  From randomization up to 108 weeks

Secondary Outcomes (16)

• Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set

  From randomization up to 108 weeks

• Proportion of Participants With Impending Relapse

  Week 24

• Number of Participants Who Maintain Stability at the Endpoint

  At the endpoint (up to 108 weeks)

• Number of Participants Achieving Remission at the Endpoint

  At Endpoint (up to 108 weeks)

• Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint

  At the Endpoint (up to 108 weeks)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

TV-46000 q1m

EXPERIMENTAL

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.

Drug: TV-46000

TV-46000 q2m

EXPERIMENTAL

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.

Drug: TV-46000; Drug: Placebo

Interventions

TV-46000 DRUG

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

Also known as: Risperidone

TV-46000 q1m; TV-46000 q2m

Placebo DRUG

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

Placebo; TV-46000 q2m

Eligibility Criteria

• Age: 13 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (81)

Teva Investigational Site 14769

Little Rock, Arkansas, 72211, United States

Location

Teva Investigational Site 14796

Rogers, Arkansas, 72758, United States

Location

Teva Investigational Site 14811

Anaheim, California, 92805, United States

Location

Teva Investigational Site 14794

Bellflower, California, 90706, United States

Location

Teva Investigational Site 14776

Colton, California, 92324, United States

Location

Teva Investigational Site 14767

Costa Mesa, California, 92626, United States

Location

Teva Investigational Site 14802

Costa Mesa, California, 92627, United States

Location

Teva Investigational Site 14773

Culver City, California, 90230, United States

Location

Teva Investigational Site 14835

Garden Grove, California, 92845, United States

Location

Teva Investigational Site 14774

Glendale, California, 91206, United States

Location

Teva Investigational Site 14817

La Habra, California, 90631, United States

Location

Teva Investigational Site 14771

Lemon Grove, California, 91945, United States

Location

Teva Investigational Site 14823

Long Beach, California, 90822, United States

Location

Teva Investigational Site 14816

Montclair, California, 91763, United States

Location

Teva Investigational Site 14803

Norwalk, California, 90650, United States

Location

Teva Investigational Site 14786

Oakland, California, 94607, United States

Location

Teva Investigational Site 14797

Oceanside, California, 92054, United States

Location

Teva Investigational Site 14827

Oceanside, California, 92056-4515, United States

Location

Teva Investigational Site 14777

Orange, California, 92868, United States

Location

Teva Investigational Site 14815

Pico Rivera, California, 90660, United States

Location

Teva Investigational Site 14812

Riverside, California, 92506, United States

Location

Teva Investigational Site 14785

San Bernardino, California, 92408, United States

Location

Teva Investigational Site 14818

San Diego, California, 92103, United States

Location

Teva Investigational Site 14828

San Diego, California, 92103, United States

Location

Teva Investigational Site 14819

San Marcos, California, 92078, United States

Location

Teva Investigational Site 14779

Santa Ana, California, 92705, United States

Location

Teva Investigational Site 14788

Torrance, California, 90502, United States

Location

Teva Investigational Site 14768

Coral Gables, Florida, 33134, United States

Location

Teva Investigational Site 14783

Coral Gables, Florida, 33134, United States

Location

Teva Investigational Site 14836

Hallandale, Florida, 33009, United States

Location

Teva Investigational Site 14787

Hialeah, Florida, 33016, United States

Location

Teva Investigational Site 14814

Hialeah, Florida, 33018, United States

Location

Teva Investigational Site 14799

Lauderhill, Florida, 33319, United States

Location

Teva Investigational Site 14832

Miami, Florida, 33126, United States

Location

Teva Investigational Site 14810

North Miami, Florida, 33161, United States

Location

Teva Investigational Site 14831

Orange City, Florida, 32763, United States

Location

Teva Investigational Site 14806

Orlando, Florida, 32810, United States

Location

Teva Investigational Site 14837

Tampa, Florida, 33614, United States

Location

Teva Investigational Site 14824

Atlanta, Georgia, 30331, United States

Location

Teva Investigational Site 14834

Columbus, Georgia, 31904, United States

Location

Teva Investigational Site 14821

Decatur, Georgia, 30030, United States

Location

Teva Investigational Site 14770

Marietta, Georgia, 30060, United States

Location

Teva Investigational Site 14765

Chicago, Illinois, 60612, United States

Location

Teva Investigational Site 14829

Chicago, Illinois, 60640, United States

Location

Teva Investigational Site 14805

Hoffman Estates, Illinois, 60169, United States

Location

Teva Investigational Site 14825

Shreveport, Louisiana, 71101, United States

Location

Teva Investigational Site 14764

Glen Burnie, Maryland, 21061, United States

Location

Teva Investigational Site 14820

New Bedford, Massachusetts, 02740, United States

Location

Teva Investigational Site 14798

Saginaw, Michigan, 48603, United States

Location

Teva Investigational Site 14791

St Louis, Missouri, 63109, United States

Location

Teva Investigational Site 14813

St Louis, Missouri, 63128, United States

Location

Teva Investigational Site 14826

St Louis, Missouri, 63132, United States

Location

Teva Investigational Site 14790

St Louis, Missouri, 63141, United States

Location

Teva Investigational Site 14809

Las Vegas, Nevada, 89102, United States

Location

Teva Investigational Site 14792

Berlin, New Jersey, 08009, United States

Location

Teva Investigational Site 14830

Princeton, New Jersey, 08540, United States

Location

Teva Investigational Site 14772

Cedarhurst, New York, 11516, United States

Location

Teva Investigational Site 14804

New York, New York, 10029, United States

Location

Teva Investigational Site 14800

New York, New York, 10032, United States

Location

Teva Investigational Site 14784

New York, New York, 10036, United States

Location

Teva Investigational Site 14780

Staten Island, New York, 10312, United States

Location

Teva Investigational Site 14763

Cincinnati, Ohio, 45219, United States

Location

Teva Investigational Site 14782

Dayton, Ohio, 45417, United States

Location

Teva Investigational Site 14822

Oklahoma City, Oklahoma, 73112, United States

Location

Teva Investigational Site 14789

Allentown, Pennsylvania, 18104, United States

Location

Teva Investigational Site 14833

Norristown, Pennsylvania, 19403, United States

Location

Teva Investigational Site 14775

Scranton, Pennsylvania, 18503, United States

Location

Teva Investigational Site 14793

Thorndale, Pennsylvania, 19372, United States

Location

Teva Investigational Site 14778

Charleston, South Carolina, 29407, United States

Location

Teva Investigational Site 14781

Dallas, Texas, 75231, United States

Location

Teva Investigational Site 14766

Dallas, Texas, 75243, United States

Location

Teva Investigational Site 14801

Houston, Texas, 77081, United States

Location

Teva Investigational Site 14807

Irving, Texas, 75062, United States

Location

Teva Investigational Site 59148

Burgas, 8000, Bulgaria

Location

Teva Investigational Site 59152

Kazanlak, 6100, Bulgaria

Location

Teva Investigational Site 59151

Lovech, 5500, Bulgaria

Location

Teva Investigational Site 59149

Novi Iskar, 1282, Bulgaria

Location

Teva Investigational Site 59144

Sofia, 1680, Bulgaria

Location

Teva Investigational Site 59154

Varna, 9000, Bulgaria

Location

Teva Investigational Site 59150

Varna, 9020, Bulgaria

Location

Teva Investigational Site 59146

Vratsa, 3000, Bulgaria

Location

Related Publications (3)

• Kane JM, Tohami O, Franzenburg KR, Suett M, Sharon N, Merenlender-Wagner A, Eshet R, Harary E, Correll CU. Effects of Long-Term Treatment with TV-46000 on Symptom Improvement Over Time in Stabilized Patients with Schizophrenia. CNS Drugs. 2025 Nov 21. doi: 10.1007/s40263-025-01240-1. Online ahead of print.

  PMID: 41272239 DERIVED

• 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 Nov;39(11):1139-1156. doi: 10.1007/s40263-025-01197-1. Epub 2025 Jul 29.

  PMID: 40730715 DERIVED

• 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.

  PMID: 37924833 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2018
• First Posted: April 19, 2018
• Study Start: April 27, 2018
• Primary Completion: September 30, 2020
• Study Completion: December 3, 2020
• Last Updated: March 10, 2023
• Results First Posted: December 9, 2021

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

US (73); BU (8)