A Phase 1, Single Dose, Parallel Cohort Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TV-44749, Olanzapine for Extended-Release Injectable Suspension for Subcutaneous Use, in Chinese Patients With Schizophrenia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 11
- 主要终点
- Period 2: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
Primary Objective:
To evaluate the safety and tolerability of single doses of TV-44749 for subcutaneous (sc) use in Chinese participants with schizophrenia.
Secondary Objectives:
- To evaluate the pharmacokinetics (PK) of single doses of TV-44749 administered sc.
- To evaluate the pharmacokinetics of oral olanzapine tablets following multiple dose administration.
- To monitor the safety and tolerability of multiple doses of oral olanzapine tablets given in the study.
详细描述
The total study duration for participants is planned to be approximately 13 weeks, including 40 days of screening, 1-week oral olanzapine treatment, a 1-week washout period, 4-week TV-44749 treatment, and 2-week follow-up period after the last dosing interval.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Body weight >50 kg and body mass index (BMI) between 18.5 to 38.0 kg/m2, inclusive, at the time of screening.
- •A current confirmed diagnosis of schizophrenia according to an evaluation by the investigator, using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
- •Are clinically stable, on oral olanzapine (i.e., dose has not changed in the last 4 weeks), and not currently on other antipsychotic treatment at the time of screening.
- •No hospitalization for worsening of schizophrenic symptoms and no significant exacerbation of schizophrenic symptoms, as judged by the investigator, within the 3 months prior to screening.
- •Female participants must have a negative serum pregnancy test at screening, are sterile or postmenopausal, and not planning pregnancy within the study period and for an additional 6 months after last dose administration.
- •Male participants must be surgically sterile, or, if capable of producing offspring, has exclusively same-sex partners or is currently using an approved method of birth control.
- •Agree to maintain current smoking or nonsmoking status at the time informed consent is obtained and throughout the study until completion of the end of study (EOS)/early termination (ET) visit.
- •Have no ongoing or expected significant life events (such as pending loss of housing, marital status change, long travel abroad, surgery, etc.) that could affect study outcomes expected throughout the period of study participation.
- •NOTE: Additional criteria apply, please contact the investigator for more information.
排除标准
- •Presence or have a history of clinically significant diseases of the renal, hepatic, gastrointestinal, cardiovascular, musculoskeletal system or presence or history of clinically significant immunological, endocrine, metabolic, neurological, or psychiatric disorder(s) (other than schizophrenia), or a history of any illness that, in the opinion of the principal investigator, might pose additional risk to the participant by participation in the study or confound the results of the study
- •Major trauma or surgery in the 2 months before screening or at any time between screening and the first dose of the investigational medicinal product (IMP), surgery scheduled during the study or follow-up period, or open biopsy within 4 months prior to screening
- •History of malignancy or treatment of malignancy in the last 5 years, excluding resected basal cell or squamous cell carcinoma of the skin.
- •NOTE: Additional criteria apply, please contact the investigator for more information.
研究组 & 干预措施
Olanzapine Dose 1
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive subcutaneous (sc) injection of TV-44749
干预措施: TV-44749 (Drug)
Olanzapine Dose 1
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive subcutaneous (sc) injection of TV-44749
干预措施: Oral Olanzapine (Drug)
Olanzapine Dose 2
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive sc injection of TV-44749
干预措施: TV-44749 (Drug)
Olanzapine Dose 2
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive sc injection of TV-44749
干预措施: Oral Olanzapine (Drug)
Olanzapine Dose 3
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive sc injection of TV-44749
干预措施: TV-44749 (Drug)
Olanzapine Dose 3
Period 1: Participants will receive oral olanzapine daily
Period 2: Participants will receive sc injection of TV-44749
干预措施: Oral Olanzapine (Drug)
结局指标
主要结局
Period 2: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
时间窗: Day 1 Up to Day 43
Period 2: Number of Participants with Treatment Emergent Serious Adverse Events (SAEs)
时间窗: Day 1 Up to Day 43
Period 2: Number of Participants with Injection Site Adverse Events
时间窗: Day 1 Up to Day 43
Period 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: Day 1 Up to Day 43
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all serious AEs (SAEs), regardless of causality is located in the Reported AE section.
Period 2: Number of Participants With Treatment Emergent SAEs
时间窗: Day 1 Up to Day 43
An AE was defined as any untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. The SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. Treatment-emergent AEs were defined as AEs that occurred after the first dose of study drug was administered in Period 1 through end of the trial. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section.
Period 2: Number of Participants With Injection Site AEs
时间窗: Day 1 Up to Day 43
Injection site AEs included injection site pruritus, induration, warmth, and abscess. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Reported AE section. All injection site AEs are reported in this outcome measure and the AE module only reports non-serious AEs at the 5% threshold. In the AE module, a participant could have been included for multiple injection site AEs.
次要结局
- Period 2: Maximum Observed Plasma Drug Concentration (Cmax) of TV-44749(Day 1 Up to Day 43)
- Period 2: Area Under the Plasma Drug Concentration versus Time Curve (AUC) of TV-44749(Day 1 Up to Day 43)
- Period 2: AUC of TV-44749 Extrapolated to Infinity (AUC0-∞)(Day 1 Up to Day 43)
- Period 1: Number of Participants with TEAEs(Day 1 Up to Day 7)
- Period 1: Time to Maximum Concentration of Oral Olanzapine at Steady State (Tmax,ss[oral olanzapine])(Day 7)
- Period 1: AUC of Oral Olanzapine at Steady State (AUC0-τ,ss[oral olanzapine])(Day 7)
- Period 1: Calculated AUC of Oral Olanzapine at Steady State Extrapolated Over 28 Days (AUC0-τ,ss[oral olanzapine] × 28)(Day 7)
- Period 1: Number of Participants with Treatment Emergent SAEs(Day 1 Up to Day 7)
- Period 2: Time to Maximum Observed Concentration (Tmax) of TV-44749(Day 1 Up to Day 43)
- Period 2: Apparent Elimination Half-Life (t½) of TV-44749(Day 1 Up to Day 43)
- Period 1: Maximum Observed Plasma Drug concentration at Steady State (Cmax,ss[oral olanzapine])(Day 7)
- Period 1: AUC of Oral Olanzapine From Time 0 to the End of the Dosing Interval (24 Hour) at Steady State (AUC0-tau,ss[Oral Olanzapine])(Day -8)
- Period 2: Area Under the Plasma Drug Concentration-time Curve (AUC) Over the Period Following Administration on Day 1 to the Time of the Last Measurable Concentration (AUC0-t) of TV-44749(Day 1 Up to Day 43)
- Period 2: AUC of TV-44749 Over the Period Following Administration on Day 1 Extrapolated to Infinity (AUC0-inf)(Day 1 Up to Day 43)
- Period 1: Maximum Observed Plasma Drug Concentration at Steady State (Cmax,ss[Oral Olanzapine])(Day -8)
- Period 1: Calculated AUC of Oral Olanzapine at Steady State Extrapolated Over 28 Days (AUC0-tau,ss[Oral Olanzapine] * 28)(Day -8 up to Day 20)
- Period 1: Time to Maximum Concentration of Oral Olanzapine at Steady State (Tmax,ss[Oral Olanzapine])(Day -8)
- Period 1: Number of Participants With TEAEs(Day -14 up to Day -8)
- Period 1: Number of Participants With Treatment Emergent SAEs(Day -14 up to Day -8)