A First in Human, Phase 1/1b Study of Single and Multiple Ascending Dosing Administration of NTX110253 in Healthy Participants and Participants With Stable Schizophrenia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Number of reported Adverse Events
研究概览
简要总结
This study will assess the safety, tolerability, and pharmacokinetics of NTX-253 following oral administration in both healthy adult participants as well as adult participants with stable schizophrenia.
详细描述
This study will assess the safety, tolerability, and pharmacokinetics of NTX-253 following oral administration in both healthy adult participants as well as adult participants with stable schizophrenia. NTX-253 is an investigational drug being developed for the treatment of schizophrenia. The study will consist of a single ascending dose (SAD - Part 1a) phase which will include a food effect cohort, and a cerebrospinal fluid (CSF - Part 1b) cohort in healthy volunteers. Participants will receive a single dose of either oral NTX-253 or placebo. The multiple ascending dose (MAD - Part 2) phase will follow. In Part 2, participants will be dosed for 10 consecutive days with either NTX-253 or placebo. Each phase will include sequential escalating doses in healthy volunteers. Two cohorts in the MAD phase will include stable schizophrenic adult participants who have had antipsychotic medication withdrawn for up to 8 days prior to dosing with NTX-253.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Primary Inclusion Criteria:
- •Male or non-pregnant, non-lactating female participants, ages 18-55 who are not of childbearing potential, with a truly abstinent lifestyle, or agrees to use medically acceptable forms of birth control
- •Part 1 a/b, Part 2 Cohort 7 only: Body mass index (BMI) within the range ≥18.0 to ≤30.0 kg/m2
- •Participants in the food effect cohort must be willing to eat a single high fat breakfast
- •(Part 2 only): Stable schizophrenia participants (schizophrenia cohorts only)
- •Body mass index (BMI) within the range ≥17.5 to ≤36.0 kg/m2
- •Positive and Negative Syndrome Scale (PANSS) total score <80 at screening
排除标准
- •(Part 1a/b, Part 2 Healthy): History of or current clinically significant medical or mental illness
- •Cancer diagnosis/treatment in the past 7 years
- •Acute or chronic gastrointestinal conditions that would interfere with drug tolerance or absorption
- •Any clinically significant, abnormal 12 lead ECG
- •Part 2: Any primary DSM-5TR disorder other than schizophrenia
- •Participants with schizophrenia who are considered resistant/refractory to antipsychotic treatment by history; history of clozapine use.
结局指标
主要结局
Number of reported Adverse Events
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Safety and tolerability will be assessed by the incidence and severity of treatment-emergent adverse events.
Number of Adverse Events of Special Interest (AESI)
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Safety and tolerability will be assessed by the incidence and severity of AESIs.
Number of dose limiting treatment emergent adverse events (TEAE)
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Safety and tolerability will be assessed by the incidence and severity of serious or dose limiting TEAEs.
Vital Signs: Change in blood pressure
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Blood pressure measurements
Vital Signs: Change in temperature
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Oral temperature measurement
Vital Signs: Change in respiratory rate
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Respiratory rate (number of breaths per minute) measurements
Vital Signs: Change in heart rate
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Pulse measurements.
Change in physical examination
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Investigator will perform complete physical exam and document any clinically significant conditions.
Clinical Laboratory Tests
时间窗: From baseline until Day 8 after a single dose, Day 17 (healthy volunteers) or Day 35 (participants with stable schizophrenia).
Hematology, serum chemistry, urinalysis, and coagulation tests.
次要结局
- Maximum observed plasma concentration (Cmax) [Pharmacokinetics](From baseline until up to 168 hours after a single dose, or until up to 168 hours after the last dose in the multiple dose cohorts.)
- Time of Cmax (tmax) [Pharmacokinetics](From baseline until up to 168 hours after a single dose, or until up to 168 hours after the last dose in the multiple dose cohorts.)
- Apparent terminal half-life (t1/2)(From baseline until up to 168 hours after a single dose, or until up to 168 hours after the last dose in the multiple dose cohorts.)
- Amount of unchanged drug excreted in urine (Ae) [urinary excretion)(From baseline until 72 hours after a single dose, or until the last dosing on Day 10 in the multiple dose cohort.)
- Percent of dose excreted as unchanged drug in urine (Ae%) [urinary excretion](From baseline until 72 hours after a single dose, or until the last dosing on Day 10 in the multiple dose cohort.)
- Renal clearance (Clr) [urinary excretion](From baseline until 72 hours after a single dose, or until the last dosing on Day 10 in the multiple dose cohort.)
- Maximum observed CSF concentration (Cmax, CSF) [Pharmacokinetics](From baseline until 12 hours after a single dose.)
- Time corresponding to Cmax (Tmax, CSF) [Pharmacokinetics](From baseline until 12 hours after a single dose.)
- QT/QTc potential interval prolongation and plasma concentration(From baseline until 72 hours post-dose in the single dose cohorts, then from baseline until Day 13 in the multiple dose cohorts.)