Clinical trial NCT03503318: Study to Evaluate TV-46000 as Maintenance Treatment in Adult and Adolescent Participants With Schizophrenia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2018-04-19
Enrollment: 544
Sex: ALL
Minimum age (years): 13
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set
timeFrame: From randomization up to 108 weeks
Secondary outcomes:
measure: Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set
timeFrame: From randomization up to 108 weeks
measure: Proportion of Participants With Impending Relapse
timeFrame: Week 24
measure: Number of Participants Who Maintain Stability at the Endpoint
timeFrame: At the endpoint (up to 108 weeks)
measure: Number of Participants Achieving Remission at the Endpoint
timeFrame: At Endpoint (up to 108 weeks)
measure: Observed Rate of Impending Relapse (Number of Participants With Impending Relapse) at the Endpoint
timeFrame: At the Endpoint (up to 108 weeks)
measure: Time to Impending Relapse (Number of Participants With Impending Relapse) in the Adolescent Participants
timeFrame: From randomization up to 108 weeks
measure: Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment
timeFrame: Baseline, endpoint and end of treatment (up to Week 108)
measure: Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment
timeFrame: Baseline, endpoint and end of treatment (up to Week 108)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From randomization up to 120 days after last dose of study drug (up to Week 125)
measure: Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment
timeFrame: Baseline, end of treatment (up to 108 weeks)
measure: Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment
timeFrame: Baseline, end of treatment (up to 108 weeks)
measure: Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment
timeFrame: Baseline, end of treatment (up to 108 weeks)
measure: Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline
timeFrame: Baseline, post-baseline (up to 108 weeks)
measure: Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment
timeFrame: Baseline, end of treatment (up to 108 weeks)
measure: Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment
timeFrame: Baseline, end of treatment (up to 108 weeks)
measure: Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone)
timeFrame: 1 hour prior to dosing at Baseline (Day 1) and at the end of treatment visit (up to 108 weeks)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Teva Investigational Site 14769
state: Arkansas
city: Rogers
country: United States
facility: Teva Investigational Site 14796
state: Arkansas
city: Anaheim
country: United States
facility: Teva Investigational Site 14811
state: California
city: Bellflower
country: United States
facility: Teva Investigational Site 14794
state: California
city: Colton
country: United States
facility: Teva Investigational Site 14776
state: California
city: Costa Mesa
country: United States
facility: Teva Investigational Site 14767
state: California
city: Costa Mesa
country: United States
facility: Teva Investigational Site 14802
state: California
city: Culver City
country: United States
facility: Teva Investigational Site 14773
state: California
city: Garden Grove
country: United States
facility: Teva Investigational Site 14835
state: California
city: Glendale
country: United States
facility: Teva Investigational Site 14774
state: California
city: La Habra
country: United States
facility: Teva Investigational Site 14817
state: California
city: Lemon Grove
country: United States
facility: Teva Investigational Site 14771
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 14823
state: California
city: Montclair
country: United States
facility: Teva Investigational Site 14816
state: California
city: Norwalk
country: United States
facility: Teva Investigational Site 14803
state: California
city: Oakland
country: United States
facility: Teva Investigational Site 14786
state: California
city: Oceanside
country: United States
facility: Teva Investigational Site 14797
state: California
city: Oceanside
country: United States
facility: Teva Investigational Site 14827
state: California
city: Orange
country: United States
facility: Teva Investigational Site 14777
state: California
city: Pico Rivera
country: United States
facility: Teva Investigational Site 14815
state: California
city: Riverside
country: United States
facility: Teva Investigational Site 14812
state: California
city: San Bernardino
country: United States
facility: Teva Investigational Site 14785
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 14818
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 14828
state: California
city: San Marcos
country: United States
facility: Teva Investigational Site 14819
state: California
city: Santa Ana
country: United States
facility: Teva Investigational Site 14779
state: California
city: Torrance
country: United States
facility: Teva Investigational Site 14788
state: California
city: Coral Gables
country: United States
facility: Teva Investigational Site 14768
state: Florida
city: Coral Gables
country: United States
facility: Teva Investigational Site 14783
state: Florida
city: Hallandale Beach
country: United States
facility: Teva Investigational Site 14836
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 14787
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 14814
state: Florida
city: Lauderhill
country: United States
facility: Teva Investigational Site 14799
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 14832
state: Florida
city: North Miami
country: United States
facility: Teva Investigational Site 14810
state: Florida
city: Orange City
country: United States
facility: Teva Investigational Site 14831
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 14806
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 14837
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 14824
state: Georgia
city: Columbus
country: United States
facility: Teva Investigational Site 14834
state: Georgia
city: Decatur
country: United States
facility: Teva Investigational Site 14821
state: Georgia
city: Marietta
country: United States
facility: Teva Investigational Site 14770
state: Georgia
city: Chicago
country: United States
facility: Teva Investigational Site 14765
state: Illinois
city: Chicago
country: United States
facility: Teva Investigational Site 14829
state: Illinois
city: Hoffman Estates
country: United States
facility: Teva Investigational Site 14805
state: Illinois
city: Shreveport
country: United States
facility: Teva Investigational Site 14825
state: Louisiana
city: Glen Burnie
country: United States
facility: Teva Investigational Site 14764
state: Maryland
city: New Bedford
country: United States
facility: Teva Investigational Site 14820
state: Massachusetts
city: Saginaw
country: United States
facility: Teva Investigational Site 14798
state: Michigan
city: Saint Louis
country: United States
facility: Teva Investigational Site 14791
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 14813
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 14826
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 14790
state: Missouri
city: Las Vegas
country: United States
facility: Teva Investigational Site 14809
state: Nevada
city: Berlin
country: United States
facility: Teva Investigational Site 14792
state: New Jersey
city: Princeton
country: United States
facility: Teva Investigational Site 14830
state: New Jersey
city: Cedarhurst
country: United States
facility: Teva Investigational Site 14772
state: New York
city: New York
country: United States
facility: Teva Investigational Site 14804
state: New York
city: New York
country: United States
facility: Teva Investigational Site 14800
state: New York
city: New York
country: United States
facility: Teva Investigational Site 14784
state: New York
city: Staten Island
country: United States
facility: Teva Investigational Site 14780
state: New York
city: Cincinnati
country: United States
facility: Teva Investigational Site 14763
state: Ohio
city: Dayton
country: United States
facility: Teva Investigational Site 14782
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 14822
state: Oklahoma
city: Allentown
country: United States
facility: Teva Investigational Site 14789
state: Pennsylvania
city: Norristown
country: United States
facility: Teva Investigational Site 14833
state: Pennsylvania
city: Scranton
country: United States
facility: Teva Investigational Site 14775
state: Pennsylvania
city: Thorndale
country: United States
facility: Teva Investigational Site 14793
state: Pennsylvania
city: Charleston
country: United States
facility: Teva Investigational Site 14778
state: South Carolina
city: Dallas
country: United States
facility: Teva Investigational Site 14781
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 14766
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 14801
state: Texas
city: Irving
country: United States
facility: Teva Investigational Site 14807
state: Texas
city: Bourgas
country: Bulgaria
facility: Teva Investigational Site 59148
city: Kazanlak
country: Bulgaria
facility: Teva Investigational Site 59152
city: Lovech
country: Bulgaria
facility: Teva Investigational Site 59151
city: Novi Iskar
country: Bulgaria
facility: Teva Investigational Site 59149
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59144
city: Varna
country: Bulgaria
facility: Teva Investigational Site 59154
city: Varna
country: Bulgaria
facility: Teva Investigational Site 59150
city: Vratsa
country: Bulgaria
facility: Teva Investigational Site 59146
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: