NCT04787302已完成1 期
A Phase 1, Open-label Trial to Evaluate Target Occupancy of CVL-231 at Muscarinic Receptors Type 4 in Brain Following Single Oral Doses Using Positron Emission Tomography in Healthy Adult Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- M4 receptor occupancy in the striatum following single oral doses of CVL-231 in healthy adult subjects
研究概览
简要总结
PET Trial to Evaluate Target Occupancy of CVL-231 at Muscarinic Receptors Type 4 in Brain Following Oral Dosing
详细描述
CVL-231 is a muscarinic acetylcholine receptor (mAChR) activator that selectively binds to the M4 muscarinic receptor subtype (M4 mAChR). CVL-231 is being developed for treatment of psychosis in schizophrenia. The aim of this trial is to characterize the relationship between the M4 receptor occupancy in different regions of the brain following a single oral doses of CVL-231 in healthy adult subjects by positron emission tomography (PET) using the radioligand [11C]MK-6884.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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 subjects and female subjects of nonchildbearing potential, ages 18 to 55 years, inclusive, at the time of signing the ICF
- •Sexually active men with a pregnant or a nonpregnant partner of childbearing potential must agree to use a double-barrier method of birth control, including a condom, and practice contraception during treatment and through 7 days post dose
- •Capable of providing informed consent and following study requirements
排除标准
- •Subjects who answer yes on the C-SSRS or, in the opinion of the investigator, present a serious risk of suicide
- •Subjects with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological disease
- •Subjects with a 12-lead ECG demonstrating either of the following (average of 3 ECGs obtained at the Screening Visit):
- •QT interval corrected for heart rate using Fridericia's formula >450 msec
- •Left ventricular hypertrophy
- •Orthostatic hypotension, which is defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the immediately previous supine/semi-recumbent blood pressure at Screening or at the prescan time point prior to baseline PET scan.
- •Subjects with a current or past personal history of any psychiatric disorder as classified by DSM-5 criteria or immediate family members with any psychiatric disorder as classified by DSM-5 criteria that require treatment
- •Subjects with a history of substance or alcohol-use disorder (DSM-5 criteria) within 2 years prior to signing the ICF
- •Subjects with other abnormal laboratory test results, vital sign results, or ECG findings
- •Subjects who currently use or have used tobacco or nicotine-containing products within 30 days prior to signing the ICF
- •Subjects with history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure (5 rem per year)
- •Subjects with any anatomical abnormality in the head that would either preclude or tend to confound the analysis of study data, including any clinically significant abnormal findings from MRI of the head
- •Current, past or anticipated exposure to radiation in the workplace
- •Any subject with a significant acute illness within 7 days prior to administration of study drug or have had a major illness or hospitalization within 1 month prior to administration of study drug
- •Any subject who, in the opinion of the sponsor, investigator, or medical monitor, should not participate in the trial
研究组 & 干预措施
CVL-231
Experimental
干预措施: CVL-231 (Drug)
结局指标
主要结局
M4 receptor occupancy in the striatum following single oral doses of CVL-231 in healthy adult subjects
时间窗: Day 1
Fraction of M4 receptors occupied by CVL-231 doses
次要结局
- Treatment-emergent adverse events(Upto 9 weeks)
- AUCscan duration for CVL-231(Day 1 (0.5, 1.5 and 2.0 hours))
- Number of subjects with Clinically significant changes in Electrocardiogram(Screening, Pre-scan, Day-1, Day 1 (T=0hour), Day 1 (T=0.5hour), Day 1 (T=3.0hour), Day 2 (T=24hour), Day 10)
- Suicidality assessed using the Columbia-Suicide Severity Rating Scale(Screening, Day-1, Day 2, Day 10)
- Model estimated Emax and EC50 at M4 receptors in striatum for CVL-231(Day 1)
- Number of subjects with clinical significant Clinical laboratory assessments(Screening, Pre-scan, Day-1, Day 2 (T=24hour))
- Number of subjects with Clinically significant changes in Vital signs(Screening, Day-1 (T=1hour), Day-1 (T=1.5hour), Day-1, Day 1 (T=0hour), Day 1(T=1.5hour), Day 1 (T=3hour), Day 1 (T=6hr), Day 1 (T=8.0), Day 2 (T-=24hr), Day 10)
- Number of subjects with clinically significant Physical and neurological examination results(Screening, Day-1 pre-scan, Day-1, Day 2)
- Cmax during scan for CVL-231(Day 1 (0.5, 1.5 and 2.0 hours))
- Cavg/Scan duration for CVL-231(Day 1 (0.5, 1.5 and 2.0 hours))
研究者
研究点 (2)
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