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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 544
- 试验地点
- 81
- 主要终点
- Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 13 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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-
- •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
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
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.
干预措施: TV-46000 (Drug)
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.
干预措施: TV-46000 (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Time to Impending Relapse (Number of Participants With Impending Relapse) for Intent-to-treat [ITT] Analysis Set
时间窗: From randomization up to 108 weeks
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).
次要结局
- Change From Baseline in Clinical Global Impression-Severity of Suicidality (CGI-SS) Score at the End of Treatment(Baseline, end of treatment (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))
- Time to Impending Relapse (Number of Participants With Impending Relapse) for Extended ITT [eITT] Analysis Set(From randomization 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))
- Change From Baseline in Calgary Depression Scale for Schizophrenia (CDSS) Score at the End of Treatment(Baseline, end of treatment (up to 108 weeks))
- Time to Impending Relapse (Number of Participants With Impending Relapse) in the Adolescent Participants(From randomization up to 108 weeks)
- Change From Baseline in Drug Attitudes Inventory 10-item Version (DAI-10) Total Score at the Endpoint and End of Treatment(Baseline, endpoint and end of treatment (up to Week 108))
- Change From Baseline in Schizophrenia Quality of Life Scale (SQLS) Total Score at the Endpoint and End of Treatment(Baseline, endpoint and end of treatment (up to Week 108))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From randomization up to 120 days after last dose of study drug (up to Week 125))
- Change From Baseline in Total Abnormal Involuntary Movement Scale (AIMS) Score at the End of Treatment(Baseline, end of treatment (up to 108 weeks))
- Change From Baseline in Simpson-Angus Scale (SAS) Mean Score at the End of Treatment(Baseline, end of treatment (up to 108 weeks))
- Change From Baseline in Total Barnes Akathisia Rating Scale (BARS) Score at the End of Treatment(Baseline, end of treatment (up to 108 weeks))
- Number of Participants Reporting Suicidal Behavior and Suicidal Ideation Using Columbia-Suicide Severity Rating Scale (C-SSRS) at Baseline and Post-Baseline(Baseline, post-baseline (up to 108 weeks))
- Plasma Concentration of Risperidone, 9-OH-risperidone, and Total Active Moiety (Sum of Risperidone and 9-OH-risperidone)(1 hour prior to dosing at Baseline (Day 1) and at the end of treatment visit (up to 108 weeks))