A Phase I Study of [18F]Flortaucipir PET Imaging in Chinese Subjects: Safety, Pharmacokinetics, Biodistribution, Radiation Dosimetry, and Preliminary Diagnostic Efficacy

Phase 1RecruitingNCT07580703

Eli Radiopharma18 enrolled

Overview

This is a non randomized, open-label Phase I study in Chinese participants. The goal of this clinical trial is to evaluate the safety and tolerability of a radioactive imaging agent called \[18F\]Flortaucipir Injection, which is used during a PET scan. The study will also measure how the agent moves through the body (pharmacokinetics), where it goes (biodistribution), the amount of radiation exposure (radiation dosimetry), and how well it may help detect signs of disease (preliminary diagnostic efficacy).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

AD - Alzheimer's Disease MCI

Interventions

A radioactive diagnostic agent intended for brain positron emission tomography (PET) imaging in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD), to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs).

Eligibility

Sex: ALLMin age: 50 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Signed informed consent form (ICF). * Male or female aged 50-85 years. * Education level sufficient to cooperate with neuropsychological testing and obtain reliable results. * Meet the following criteria related to cognitive impairment: 1. CN: No history of cognitive impairment, Aβ-PET negative, MRI without clinically significant neurodegenerative changes. 2. MCI: Meet core criteria for AD-related MCI, Aβ-PET positive, MRI showing neurodegenerative changes. 3. AD: Meet core criteria for probable AD dementia, Aβ-PET positive, MRI showing neurodegenerative changes. * Fertile individuals: No plan for reproduction, sperm/egg donation within 6 months after signing ICF and until 6 months after study drug administration; and agreement to use highly effective contraception (including partner). Exclusion Criteria: * Pregnant (positive pregnancy test at screening or before administration) or breastfeeding women. * Major surgery within 1 month prior to screening, or planned surgery during the study period. * Known allergy to radioactive radiation, alcohol, \[18F\]Flortaucipir injection, or its excipients, or other severe allergic reactions. * Cognitive impairment due to causes other than AD. * Clinically significant infarction or probable multi-infarct dementia. * Current clinically significant psychiatric illness (e.g., major depression, schizophrenia). * History of epilepsy or seizures (except febrile seizures in childhood). * Inability to tolerate PET/MRI or presence of contraindications to PET/MRI. * Other neurodegenerative diseases or dementias other than AD dementia. * Any other condition that, in the investigator's opinion, makes the subject unsuitable for the study.

Outcomes

Primary Outcomes

Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)

Time frame: 6 days post-injection

Secondary Outcomes

Maximum Observed Plasma Concentration (Cmax) - Total Radioactivity and Parent Compound

Cmax is defined as the highest observed plasma concentration of total radioactivity (measured by gamma counting) and of the unmetabolized parent \[18F\]Flortaucipir

Time frame: Up to 360 mins

Time to Reach Cmax (Tmax) - Total Radioactivity and Parent Compound

Tmax is the time (in minutes) at which the maximum plasma concentration (Cmax) occurs, recorded as the midpoint of the sampling interval during which the maximum is observed.

Time frame: Up to 360 mins

Terminal Half-Life (t½) of Unmetabolized Parent Compound

Time frame: Up to 360 mins

Area Under the Plasma Concentration-Time Curve (AUC0-t and AUC0-∞) of Unmetabolized Parent Compound

AUC0-t is calculated using the linear trapezoidal rule from time 0 to the last measurable concentration. AUC0-∞ is extrapolated as AUC0-t + Ct/λz, where Ct is the last quantifiable concentration and λz is the terminal elimination rate constant.

Time frame: Up to 360 mins

Percentage of Unmetabolized Parent Compound in Plasma

Time frame: Up to 360 mins

Urinary Radioactive Excretion Rate

Rate of radioactivity excreted in urine, expressed as percentage of injected dose per hour (%ID/h). Measured by gamma counting of collected urine aliquots over specified intervals.

Time frame: 0-60, 60-120, 120-240, 240-360 mins post-injection

Cumulative Urinary Excretion of Radioactivity

Total cumulative percentage of the injected radioactive dose recovered in urine over time. Calculated as the sum of radioactivity excreted at each collection interval.

Time frame: Up to 360 mins post-injection

Percentage of Unmetabolized Parent Compound and Metabolites in Urine

Relative proportion of total urinary radioactivity that corresponds to the intact \[18F\]Flortaucipir and its known radioactive metabolites.

Time frame: Up to 360 mins post-injection

Organ/Tissue Radioactivity Uptake - Percent Injected Dose (%ID)

Percentage of the injected radioactive dose (%ID) present in each target organ or tissue (e.g., brain, liver, kidneys, lungs, bone marrow, etc.) at specified imaging time points.