An Open-label, Positron Emission Tomography Study to Evaluate Brain Receptor Occupancy, Safety, Tolerability, and Pharmacokinetics After a Single Sublingual Administration of ITI-1284 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- % Receptor occupancy
研究概览
简要总结
The study will be conducted as an open-label and single-center study to evaluate the occupancy of ITI-1284 to the dopamine D2 receptor, serotonin 2A (5-HT2A) receptor, and serotonin transporter (SERT) in healthy subjects.
详细描述
This study consists of up to 3 sequential parts. Part A will evaluate the D2 receptor occupancy for ITI-1284 at three dose levels. Part B will evaluate the 5HT-2A receptor and SERT occupancy for ITI-1284 at one dose level. Part C will evaluate the late postdose receptor occupancy of ITI-1284 on the D2 or 5-HT2A receptor at one dose level.
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 55 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 55 years old (inclusive);
- •BMI inclusive of 18-32 kg/m2 at screening and a minimum weight of 50 kg;
- •Willingness to remain in the hospital research unit for the duration of the inpatient period.
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, pulmonary, endocrinologic, hematologic, or immunologic disease or history of malignancy;
- •Clinically significant abnormal findings in vital sign assessments, supine SBP > 140 mmHg or < 90 mmHg, or supine DBP >90 mmHg or < 50 mmHg or supine pulse rate > 100 bpm or < 45 bpm at Screening;
- •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);
- •Contraindications based on any previous MRI or the study MRI performed prior to the baseline PET/CT scan.
研究组 & 干预措施
Cohort A2: 20 mg ITI-1284
Radioligand: [11C]-raclopride
干预措施: ITI-1284 20 mg (Drug)
Cohort A1: 10 mg ITI-1284
Radioligand: [11C]-raclopride
干预措施: ITI-1284 10 mg (Drug)
Cohort B1: 20 mg ITI-1284
Radioligand: [11C]-MDL100907
干预措施: ITI-1284 20 mg (Drug)
Cohort B2: 20 mg ITI-1284
Radioligand: [11C]-DASB
干预措施: ITI-1284 20 mg (Drug)
Cohort A3: 30 mg ITI-1284
Radioligand: [11C]-raclopride
干预措施: ITI-1284 10 mg (Drug)
Cohort A3: 30 mg ITI-1284
Radioligand: [11C]-raclopride
干预措施: ITI-1284 20 mg (Drug)
Cohort C1: 20 mg ITI-1284
Radioligand: [11C]-raclopride or [11C]-MDL100907
干预措施: ITI-1284 20 mg (Drug)
结局指标
主要结局
% Receptor occupancy
时间窗: Day 1
Percent change of binding potential from baseline
次要结局
- Pharmacokinetics: AUC0-t(Day 1)
- Pharmacokinetics: Cmax(Day 1)
- Pharmacokinetics: Tmax(Day 1)
- Percentage of subjects with treatment-emergent adverse events(Up to 30 days after the dose of study drug)
- Change from baseline in ECG QT interval(Day 3)
- Change from baseline in aspartate aminotransferase(Day 3)
- Change from baseline in alanine aminotransferase(Day 3)