Exploratory Evaluation of Flortaucipir Injection in Healthy Volunteers and Cognitively Impaired Subjects
- Conditions
- Alzheimer Disease
- Interventions
- Procedure: Brain PET ScanProcedure: Whole body PET scanProcedure: Brain MRI
- Registration Number
- NCT04474405
- Lead Sponsor
- Avid Radiopharmaceuticals
- Brief Summary
This early phase 1 study explored the brain uptake, retention, and safety of flortaucipir and obtained preliminary information regarding dosimetry of flortaucipir.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
- Healthy volunteers had an Mini-Mental State Examination (MMSE) score of ≥ 29;
- MCI due to Alzheimer's disease (AD) consistent with National Institute on Aging (NIA)-Alzheimer's Association working group's on diagnostic guidelines for AD (Alzheimer's Dementia 7:270-9, 2011)
- Possible or probable AD: Met clinical criteria for possible or probable AD based on the NIA-Alzheimer's Association working group's on diagnostic guidelines for AD (Alzheimer's Dementia 7:263-9, 2011)
- Current clinically significant psychiatric disease.
- Evidence of structural abnormalities such as major stroke or mass on MRI that would have made a diagnosis of impairment due to AD unlikely or was likely to interfere with interpretation of a PET scan on MRI.
- Claustrophobic or otherwise unable to tolerate the imaging procedure.
- Current clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram (including, but not limited to, corrected QT interval >450 msec).
- Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer
- History of alcohol abuse or substance abuse or dependence
- Female subjects of childbearing potential who were not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception.
- Required medications with a narrow therapeutic window
- Received a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to imaging session
- Receiving any investigational medications or had participated in a trial with investigational medications within the last 30 days
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Brain flortaucipir PET scan Brain PET Scan Subjects receiving a brain PET scan after flortaucipir administration Brain flortaucipir PET scan Brain MRI Subjects receiving a brain PET scan after flortaucipir administration Whole body flortaucipir PET scan Whole body PET scan Subjects receiving a whole body PET scan after flortaucipir administration MRI and Amyloid Extension Cohort Brain PET Scan Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000 (NCT01733355) MRI and Amyloid Extension Cohort Brain MRI Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000 (NCT01733355) Brain flortaucipir PET scan Flortaucipir F18 Subjects receiving a brain PET scan after flortaucipir administration Whole body flortaucipir PET scan Flortaucipir F18 Subjects receiving a whole body PET scan after flortaucipir administration MRI and Amyloid Extension Cohort Florbetapir F 18 Magnetic resonance imaging (MRI) scans and amyloid scans for subjects previously participating in Study T807000 (NCT01733355) Brain flortaucipir PET scan Florbetapir F 18 Subjects receiving a brain PET scan after flortaucipir administration
- Primary Outcome Measures
Name Time Method Brain Flortaucipir Uptake 80-100 minutes postdose Brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVr), normalized to the entire cerebellum. A global cortical average volume of interest (VOI) is the average SUVr of the occipital cortex, parietal cortex, and temporal cortex. For SUVr, a value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Flortaucipir Whole Body Effective Dose injection to 6 hours postdose Radiation dose estimates measured in millisieverts per megabecquerel (mSv/MBq) for the whole body obtained from Organ Level Internal Dose Assessment/Exponential Modeling (OLINDA/EXM) radiation dosimetry code. Results calculated using 73.7-kg man model.
- Secondary Outcome Measures
Name Time Method Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Digit Symbol Substitution Test) at baseline Spearman's correlations between flortaucipir SUVr and cognitive function as measured on Digit Symbol Substitution Test (DSST). The DSST is sensitive to the presence of cognitive dysfunction as well as to change in cognitive function. Scores range from 0 to 133. Lower DSST scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.
Flortaucipir PET Correlations With Cognitive Assessments (Mini-mental State Exam) at baseline Spearman's correlations between flortaucipir SUVr and cognitive function as measured on the Mini-Mental State Examination (MMSE). MMSE is a 30-point questionnaire that is used to measure cognitive impairment. 0 is the lowest score and 30 is the highest score, indicating normal cognitive function. Lower MMSE scores indicate worsening cognitive function. For this analysis, negative correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and positive correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.
Flortaucipir PET Correlations With Cognitive Assessments Cognitive Assessments (Alzheimer's Disease Assessment Scale) at baseline Spearman's correlations between flortaucipir SUVr and cognitive function as measured on a Modified Alzheimer's Disease Assessment Scale (ADAS)-Cognitive subscale (including orientation, verbal memory, language, and praxis, minus the spoken language assessment). Scores on the modified scale can range from 0 to 65. Higher scores indicate worsening cognitive function. For this analysis, positive correlation values indicate that higher flortaucipir uptake is associated with decreasing cognitive function and negative correlation values indicate that lower flortaucipir uptake is associated with better cognitive function. 95% confidence interval uses a Fisher's z transformation.
Trial Locations
- Locations (2)
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
WCCT Global, LLC
🇺🇸Cypress, California, United States