A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study With an Open-Label, Long-Term Safety Phase to Evaluate the Efficacy, Safety, and Tolerability of Olanzapine for Extended-Release Injectable Suspension (TV-44749) for Subcutaneous Use as Treatment of Adult Patients With Schizophrenia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 675
- 试验地点
- 118
- 主要终点
- Double-blind Period: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 8
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of TV-44749 in adult participants with schizophrenia.
A key secondary objective is to further evaluate the efficacy of TV-44749 based on additional parameters in adult participants with schizophrenia.
A secondary objective is to evaluate the safety and tolerability of TV-44749 in adult participants with schizophrenia
Another secondary objective of this study is to evaluate the efficacy of TV-44749 from baseline to endpoint in Period 1 in adult participants with schizophrenia.
Total study duration is up to 61 weeks, and treatment duration is up to 56 weeks, with weekly visits during the first 8 weeks and then monthly in-clinic visits with weekly calls during the remainder of the treatment period.
详细描述
Participants with exacerbation of schizophrenia may be included. The study will be composed of 2 periods: Period 1 (the double-blind, placebo-controlled, efficacy and safety period) and Period 2 (open-label long term safety period). For each participant, the duration of Period 1 will be 8 weeks, and the duration of Period 2 will be up to 48 weeks. In Period 1, participants will be randomized to one of 3 TV-44749 treatment groups or a placebo group in a 1:1:1:1 ratio. All participants will be randomized again to one of the TV44749 treatment groups in a 1:1:1 ratio for Period 2. The end-of-treatment and follow-up visits will be at 4 and 8 weeks after the last dose of investigational medicinal product administration, respectively.
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
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant has a current confirmed diagnosis of schizophrenia according to the DSM-5, for >1 year
- •The participant has exacerbation of schizophrenia that started ≤8 weeks prior to screening and would benefit from psychiatric hospitalization or continued hospitalization for symptoms of schizophrenia.
- •Participants who have received an antipsychotic treatment (other than clozapine) in the past year must have been responsive based on the investigator's judgment (and based on discussions with family members, caregivers, or healthcare professionals, as applicable).
- •Body mass index between 18.0 and 40.0 kg/m2, inclusive, at the time of screening
- •Women may be included only if they have a negative beta-human chorionic gonadotropin (β-HCG) test at screening and baseline
- •Women of childbearing potential 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 prior to the first administration of IMP, and agree to continue the use of this method for the duration of the study, and for 70 days after the last dose of IMP
- •The participant is in adequate health as determined by medical and psychiatric history, medical examination, electrocardiogram (ECG), serum chemistry, hematology, coagulation urinalysis, and serology.
- •NOTE- Additional criteria apply, please contact the investigator for more information
排除标准
- •The participant has a current clinically significant DSM-5 diagnosis other than schizophrenia (has a primary current diagnosis other than schizophrenia or a comorbid diagnosis that is primarily responsible for the current symptoms and functional impairment).
- •The participant has a known history of the following: (a) borderline personality disorder, antisocial personality disorder, or bipolar disorder; (b) traumatic brain injury causing ongoing cognitive difficulties, Alzheimer's disease, or another form of dementia, or any chronic organic disease of the central nervous system; and (c) intellectual disability of a severity that would impact ability to participate in the study.
- •The participant was hospitalized for >14 days (with the exception of social or administrative hospitalization) in the current exacerbation episode prior to screening.
- •The participant has a significant risk of violent behavior based on the participant's medical history or investigator's judgment.
- •The participant has a significant risk of committing suicide based on the participant's medical history or C-SSRS, and the investigator's judgment.
- •The participant is currently using an LAI antipsychotic or is still under the coverage period of the specific LAI at time of screening.
- •The participant has taken clozapine or has received electroconvulsive therapy within the last 12 months prior to screening.
- •The participant is currently receiving daily oral olanzapine at a dose >20 mg/day.
- •The participant has current or a history of known hypersensitivity to olanzapine or any of the excipients of TV-44749 or the oral formulation of olanzapine.
- •The participant has had a significant sedation or delirium after antipsychotic treatment according to medical and psychiatric history and as judged by the investigator or suffered from delirium due to a medical condition.
- •The participant has a non-fasting glucose level of ≥200 mg/dL at screening
- •The participant meets criteria for moderate to severe substance use disorder (based on DSM-5 criteria) within the past 6 months (excluding those related to caffeine or nicotine)
- •NOTE- Additional criteria apply, please contact the investigator for more information
研究组 & 干预措施
Double-blind Period: Placebo
Participants will receive placebo matched to TV-44749 subcutaneously (SC) once monthly over 8 weeks in double-blind period.
干预措施: Placebo (Drug)
Double-blind Period: TV-44749 318 mg
Participants will receive TV-44749 extended-release injectable suspension at a dose of 318 milligrams (mg) SC once monthly over 8 weeks in double-blind period.
干预措施: TV-44749 (Drug)
Double-blind Period: TV-44749 425 mg
Participants will receive TV-44749 extended-release injectable suspension at a dose of 425 mg SC once monthly over 8 weeks in double-blind period.
干预措施: TV-44749 (Drug)
Double-blind Period: TV-44749 531 mg
Participants will receive TV-44749 extended-release injectable suspension at a dose of 531 mg SC once monthly over 8 weeks in double-blind period.
干预措施: TV-44749 (Drug)
Open-label Period: Placebo to TV-44749 318 mg
Participants who receive placebo during the double-blind period, will receive TV-44749 extended-release injectable suspension at a dose of 318 mg SC once monthly for up to 48 weeks in open-label period.
干预措施: TV-44749 (Drug)
Open-label Period: Placebo to TV-44749 425 mg
Participants who receive placebo during the double-blind period, will receive TV-44749 extended-release injectable suspension at a dose of 425 mg SC once monthly for up to 48 weeks in open-label period.
干预措施: TV-44749 (Drug)
Open-label Period: Placebo to TV-44749 531 mg
Participants who receive placebo during the double-blind period, will receive TV-44749 extended-release injectable suspension at a dose of 531 mg SC once monthly for up to 48 weeks in open-label period.
干预措施: TV-44749 (Drug)
结局指标
主要结局
Double-blind Period: Change in the Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 8
时间窗: Baseline, Week 8
The PANSS is a 30-item scale used to evaluate positive and negative symptoms of schizophrenia. The PANSS was used to identify the presence and severity of psychopathology symptoms, the relationship of these symptoms to one another, and the global psychopathology. Each item was scored on a 7-point scale ranging from 1 (absent) to 7 (extreme). The positive symptom scale includes 7 items with a maximum score of 49; the negative symptom scale includes 7 items with a maximum score of 49; and the general psychopathology scale includes 16 items with a maximum score of 112. The total score was the sum of 30-item scale, ranging from 30 (absent) to 210 (extreme), with a higher score indicating greater severity of symptoms. Least square (LS) mean was calculated using a repeated measures model with treatment, study visit, treatment visit interaction, stratification variables (sex and geographic region), age, and PANSS total score at baseline as covariates.
次要结局
- Double-blind Period: Change in Clinical Global Impression-Severity (CGI-S) Scale Score From Baseline to Week 8(Baseline, Week 8)
- Double-blind Period: Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 8(Baseline, Week 8)
- Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Baseline up to Week 8)
- Integrated Study Period: Number of Participants With TEAEs and SAEs(Baseline up to Week 60)
- Double-blind Period: Change in PANSS Total Score From Baseline to Weeks 1, 2, and 4(Baseline, Weeks 1, 2, and 4)
- Double-blind Period: Clinical Global Impression-Improvement (CGI-I) Scale Score at Weeks 4 and 8(Weeks 4 and 8)
- Double-blind Period: Change in CGI-S Scale Score From Baseline to Weeks 1, 2, and 4(Baseline, Weeks 1, 2, and 4)
- Double-blind Period: Patient Global Impression-Improvement (PGI-I) Scale Score at Weeks 2, 4, and 8(Weeks 2, 4, and 8)
- Double-blind Period: Change in Schizophrenia Quality of Life Scale (SQLS) Total Score From Baseline to Weeks 4 and 8(Baseline, Weeks 4 and 8)
- Double-blind Period: Change in PSP Score From Baseline to Week 4(Baseline, Week 4)
- Double-blind Period: Number of Participants Receiving At Least 1 Concomitant Medication(Baseline up to Week 8)
- Integrated Study Period: Number of Participants Receiving At Least 1 Concomitant Medication(Baseline up to Week 60)
- Double-blind Period: Change From Baseline to Week 8 in Abnormal Involuntary Movement Scale (AIMS) Total Score(Baseline, Week 8)
- Integrated Study Period: Change From Baseline to the End of Treatment (EOT) in AIMS Total Score(Baseline, EOT (up to Week 56))
- Double-blind Period: Change From Baseline to Week 8 in Simpson-Angus Scale (SAS) Mean Score(Baseline, Week 8)
- Integrated Study Period: Change From Baseline to the EOT in SAS Mean Score(Baseline, EOT (up to Week 56))
- Double-blind Period: Change From Baseline to Week 8 in Barnes Akathisia Rating Scale (BARS) Total Score(Baseline, Week 8)
- Integrated Study Period: Change From Baseline to the EOT in BARS Total Score(Baseline, EOT (up to Week 56))
- Double-blind Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline up to Week 8)
- Integrated Study Period: Number of Participants With Any Suicidal Ideation or Suicidal Behavior According to the C-SSRS(Baseline up to Week 60)
- Double-blind Period: Change From Baseline to Week 8 in Calgary Depression Scale for Schizophrenia (CDSS) Score(Baseline, Week 8)
- Integrated Study Period: Change From Baseline to the EOT in CDSS Score(Baseline, EOT (up to Week 56))
- Double-blind Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 8)
- Integrated Study Period: Number of Participants With AEs and SAEs(Baseline up to Week 60)
- Integrated Study Period: Change From Baseline to Week 60 in AIMS Total Score(Baseline, Week 60)
- Integrated Study Period: Change From Baseline to Week 60 in SAS Mean Score(Baseline, Week 60)
- Integrated Study Period: Change From Baseline to Week 60 in BARS Total Score(Baseline, Week 60)
- Integrated Study Period: Change From Baseline to Week 60 in CDSS Score(Baseline, Week 60)