A Three Part Study to Evaluate the Safety, Radiation Dosimetry, Biokinetics, and Effectiveness of [18F]MK-3328, a Radiotracer for Use in Positron Emission Tomography
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 主要终点
- Number of Participants With an Adverse Event (AE)
研究概览
简要总结
This study will estimate the radiochemical and radiation safety and assess the efficacy of [18F]MK-3328, a novel positron emission tomography (PET) tracer. The study safety hypotheses will test whether [18F]MK-3328 is sufficiently safe and well-tolerated, based on an assessment of clinical and laboratory evaluations and adverse experiences in healthy participants, including healthy elderly (HE) participants, and Alzheimer's disease (AD) participants, to permit continued investigation. The study efficacy hypothesis will test whether [18F]MK-3328 can discriminate between AD participants and cognitively normal elderly control participants based on tracer volume of distribution, or one of its surrogates, in brain posterior cingulate gyrus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant is male or female of non-reproductive potential between 50 and 65 years old.
- •Participant is less than 6'5" tall
- •Participant is in good health
- •Participant has been a non-smoker for at least 10 years
- •Parts II and III:
- •Male or female of non-reproductive potential at least 55 years of age
- •Participant is cognitively normal (HE participants), or has probable mild-to moderate AD (AD participants)
- •Participant is willing to have an arterial catheter placed in the radial artery (Part II only)
排除标准
- •Participant has a history of stroke, seizures, or neurological disorder
- •Participant has or has a history of any disease or condition, or takes any medication that would interfere with assessment of the tracer or make participation unsafe or unduly uncomfortable
- •Parts II and III:
- •Participant has a history or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with altered cognition
- •Participant has or has a history of any disease or condition, or takes any medication that would interfere with assessment of the tracer or make participation unsafe or unduly uncomfortable
- •Participant is living in a nursing home or skilled nursing facility
研究组 & 干预措施
Part I, Healthy Participants
Healthy participants will receive a single intravenous (IV) dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part I of the study
干预措施: [18F]MK-3328 (Drug)
Part II, HE and AD Participants
HE and AD participants will receive a single IV dose of ~150 megabecquerel (MBq) [18F]MK-3328 in Part II of the study
干预措施: [18F]MK-3328 (Drug)
Part III, HE and AD Participants
HE and AD participants will receive two separate IV doses of ~150 megabecquerel (MBq) [18F]MK-3328 in Part III of the study
干预措施: [18F]MK-3328 (Drug)
结局指标
主要结局
Number of Participants With an Adverse Event (AE)
时间窗: Up to 14 days after last dose
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.
Number of Participants Who Discontinued Study Due to an AE
时间窗: Up to 14 days after last dose
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug.
Effective Dose of [18F]MK-3328
时间窗: Up to approximately 6 hours post dose
Using PET whole body images acquired after dosing, regions of interest (ROIs) were drawn in all organs showing visible \[18F\]MK-3328 accumulation. Time activity curves (TACs) showing total \[18F\]MK-3328 retention as a function of time were determined for each organ. Residence times were calculated from the area under each organ TAC. Radiation exposure of the body and critical organs was calculated from the \[18F\]MK-3328 residence times using OLINDA (Organ Level Internal Dose Assessment) software. For each organ, the equivalent dose, which is the absorbed radiation dose weighted for the degree of the biological effect of different types of radiation, was calculated. The total radiation exposure to the body is expressed as the effective dose, which is the sum of the equivalent doses in each organ multiplied by a weighting factor for the type of tissue exposed. Effective dose is the primary surrogate for radiation risk. The unit of effective dose is the Sievert (Sv).
Organ Effective Dose of [18F]MK-3328
时间窗: Up to approximately 6 hours post dose
Using PET whole body images acquired after dosing, ROIs were drawn in all organs showing visible \[18F\]MK-3328 accumulation. TACs showing total \[18F\]MK-3328 retention as a function of time were determined for each organ. Residence times were calculated from the area under each organ TAC. Radiation exposure of the body and critical organs was calculated from the \[18F\]MK-3328 residence times using OLINDA software. For each organ, the equivalent dose, which is the absorbed radiation dose weighted for the degree of the biological effect of different types of radiation, was calculated. The organ effective dose is the equivalent dose in each organ multiplied by a weighting factor for the type of tissue exposed. The unit of organ effective dose is Sv.
Mean Brain Cortical [18F]MK-3328 Standard Uptake Value Ratio (SUVR) in AD Participants and HE Participants
时间窗: 60-90 minutes post dose
Using PET brain images acquired after dosing, regions of interest (ROIs) were drawn in identified brain areas. The ROIs were projected onto all frames of the dynamic PET scans in order to generate \[18F\]MK-3328 tissue TACs. SUVR is calculated as the ratio of the average \[18F\]MK-3328 uptake over 60-90 minutes post dose in the target brain region and the cerebellum. Cortical SUVR is reported, which is a mean SUVR derived from SUVR from multiple brain regions (frontal cortex, parietal cortex, anterior cingulate gyrus, posterior cingulate gyrus, temporal cortex, lateral temporal cortex and occipital cortices).
Least Squares (LS) Mean [18F]MK-3328 SUVR in Brain Posterior Cingulate Gyrus in AD Participants and HE Participants
时间窗: 60-90 minutes after second dose
Using PET brain images acquired after the second dose of \[18F\]MK-3328, regions of interest (ROIs) were drawn in identified brain areas. The ROIs were projected onto all frames of the dynamic PET scans in order to generate \[18F\]MK-3328 tissue TACs. Posterior cingulate gyrus SUVR was calculated as the ratio of the average \[18F\]MK-3328 uptake over 60-90 minutes post dose in the target brain region and the cerebellum.
次要结局
未报告次要终点