An Open-label, Positron Emission Tomography (PET) Study to Evaluate Brain Receptor Occupancy, Safety, Tolerability, and Pharmacokinetics After Single Oral Doses of ITI-333 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Pharmacodynamics: 5-HT2A receptor occupancy (RO) using [11C]-MDL100907
研究概览
简要总结
This is an open-label, single-dose study of up to 4 dose levels of ITI-333 in healthy male and female subjects. Each cohort will enroll 6 subjects. Subjects will have a baseline PET/CT scan and a postdose PET/CT scan using [14C]-MDL100907 to characterize 5-HT2A receptor occupancy
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female subjects between 18 and 45 years old (inclusive);
- •BMI inclusive of 18.0-32.0 kg/m2 at screening and a minimum weight of 50 kg;
- •Willing to be confined to the clinical research unit for the duration of the inpatient period of the study;
排除标准
- •Clinically significant abnormality within 2 years of Screening that in the Investigator's opinion may place the subject at risk or interfere with study outcome variables; this includes, but is not limited to, history of or current cardiac, hepatic, renal, neurologic, gastrointestinal (including history of gastric bypass), pulmonary, endocrinologic, hematologic, or immunologic disease or history of malignancy;
- •Clinically significant abnormal findings in vital sign assessments, including blood oxygen saturation (SpO2) < 96% and respiratory rate < 12 breaths per min;
- •History of psychiatric condition that in the Investigator's opinion may be detrimental to participation in the study;
- •Any condition which would preclude MRI or PET/CT examination (eg, implanted metal, claustrophobia, unable to fit in PET/CT or MRI scanners).
研究组 & 干预措施
Cohort A1: ITI-333 2.25 mg
干预措施: ITI-333 (Drug)
Cohort A2: ITI-333 dose to be determined based on Cohort A1
干预措施: ITI-333 (Drug)
Cohort A3: ITI-333 dose to be determined based on Cohort A1 and A2
干预措施: ITI-333 (Drug)
Cohort A4: ITI-333 dose to be determined based on Cohort A1, A2 and A3
干预措施: ITI-333 (Drug)
结局指标
主要结局
Pharmacodynamics: 5-HT2A receptor occupancy (RO) using [11C]-MDL100907
时间窗: baseline 90-minute PET scan between Day -10 and Day -1, and a 90-minute PET scan starting at approximately 1 hour postdose
Pharmacokinetics: AUC0-t
时间窗: predose and multiple timepoints up to 24 hours postdose
Area under the plasma concentration time curve from time zero to the last measurable of concentration of ITI-333
Pharmacokinetics: Cmax
时间窗: predose and multiple timepoints up to 24 hours postdose
Maximum observed plasma concentration
Pharmacokinetics: Tmax
时间窗: predose and multiple timepoints up to 24 hours postdose
Time to reach maximum observed plasma concentration
次要结局
- Percentage of subjects with treatment-emergent adverse events(up to 30 days after last dose)
- Change from baseline in systolic and diastolic blood pressure(Up to Day 7)
- Change from baseline in ECG QT interval(Up to Day 7)
- Change from baseline in aspartate aminotransferase(Up to Day 7)
- Change from baseline in alanine aminotransferase(Up to Day 7)