A Study of XTR004 Radiotracer in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
XTR004 is a 18F-labeled myocardial perfusion positron emission tomography tracer use to measure myocardial perfusion and myocardial blood flow. XTR004 binds to the myocytes and targets respiratory chain complex 1 in the mitochondria.This phase I study investigated the safety, biodistribution, radiation dosimetry and Pharmacokinetics of XTR004 in 10 healthy Chinese adults volunteers.

Detailed Description
-----------------
XTR004 is a 18F-labeled myocardial perfusion PET tracer, the first one developed in China by Sinotau Pharmaceutical Group. XTR004 targets and binds to the mitochondrial complex I protein. XTR004 reflects myocardial function at a molecular level. In pre-clinical studies XTR004 demonstrated high myocardial first-pass extraction and prolonged retention, allowing for early or delayed imaging. XTR004 can be clinically used to measure myocardial perfusion and myocardial blood flow. This Phase I study will be open-labeled, nonrandomized, single center study. Enrolled 10 healthy Chinese adults who meet all of the inclusion and none of the exclusion criteria. Subjects will receive 6-8 mCi of XTR004 via IV injection. Safety and tolerability will be observed. Biodistribution, pharmacokinetics, and dosimetry will be investigated.

Official Title
-----------------
A Phase I Study to Evaluate Safety, Biodistribution, Radiation Dosimetry, and Pharmacokinetics of XTR004 in Healthy Chinese Volunteers

Conditions
-----------------
Coronary Artery Disease (CAD), Myocardial Ischemia

Intervention / Treatment
-----------------
* Diagnostic Test: XTR004


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chinese men and women are included age between 18-40 years Normal vital signs and physical examination No clinical abnormalities in ECG, EEG, and echocardiogram No past history of cardiovascular, cerebrovascular, or gastrointestinal diseases Normal or no clinical significance abnormalities in laboratory tests No any other major or chronic illness No presence of drug use Females adopt effective medically approved contraceptive methods to prevent pregnancy for at least 6 months before the study and after the study Voluntarily agree and signed written consent Exclusion Criteria: Previous history of cardiovascular diseases A history of or physical or radiographic manifestations of any previous brain disease Any previous major disease or unstable condition Subjects who cannot complete XTR004 imaging as required Positive HIV, hepatitis C or Treponema pallidum antibody and hepatitis B surface antigen detection A history of coagulation or coagulation disorder A history of liver or gastrointestinal disease or other conditions that interfere with drug absorption, distribution, excretion or metabolism as determined by the investigator Previous history of cancer High risk of drug allergic reaction A history of alcohol or drug abuse/dependence Exposure to significant occupational radiation (e.g >50 mvs/year) or exposure to radioactive substances for therapeutic or research purposes over the past 10 years Scheduled surgery or other invasive interventions within one week before drug injection Subjects use any drug or treatment that may interfere with the experimental data or cause serious side effects, as determined by the investigator Pregnant or lactating women Admitted to hospital due to illness during screening period Other conditions that investigators consider inappropriate to participate in a trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XTR004<br>Single dose 6.0-8.0 mCi intravenous injection of XTR004 and investigation of XTR004 (MPI radiotracer). | Diagnostic Test: XTR004<br>* Single dose intravenous injection of XTR004. Serial whole-body PET scan will be obtain after injection, blood and urine collection after injection for the assessment of pharmacokinetics.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical examination of the major organ systems | Safety observation: Observation of Cardiovascular system (blood pressure, pulse rate, and rhythm), Lungs (respiratory rate, chest expansion, and lung auscultation), Abdominal system (for any tenderness or organ enlargement), Nervous system ( cognitive testing, motor strength and control, including mental status), Musculoskeletal system, and Skin for any abnormalities, after drug injection. To report number of participants with changes in physical examination compared to baseline physical examination obtained before drug injection. | up to 14 days post injection | 
| 12-lead Electrocardiography | Safety observation: Observation of ECG electrical activity pattern in the P-wave, PR interval, QRS wave complex, ST segment, and T-wave if associated with any abnormality after drug injection. To observe and report participants with ECG abnormality compared to baseline ECG obtained before drug injection. | up to 14 days post injection | 
| Monitoring of body temperature | Safety observation: Vital sign monitoring of body temperature (degrees celsius ) after drug injection. To report changes in body temperature compared to baseline body temperature obtained before drug injection. | up to 14 days post injection | 
| Monitoring of respiratory rate | Safety Observation: Vital sign monitoring of respiratory rate (breath per minute) after drug injection. To report changes in respiratory rate compared to baseline respiratory rate obtained before drug injection. | up to 14 days post injection | 
| Monitoring of Blood pressure | Safety Observation: Vital sign monitoring of blood pressure (mmHg) after drug injection. To report changes in blood pressure compared to baseline blood pressure obtained before drug injection. | up to 14 days post injection | 
| Monitoring of pulse rate | Safety Observation: Vital sign monitoring of pulse rate (beats per minute) after drug injection. To report changes in pulse rate compared to baseline pulse rate obtained before drug injection. | up to 14 days post injection | 
| Changes in Laboratory tests | Safety observation: Measurements of routine blood (g/L), routine urine (mg/dL), and blood troponin-I levels (ng/ml) after drug injection. To observe and report changes in routine blood, routine urine, and blood troponin-I levels compared to baseline values obtained before drug injection. | up to 14 days post injection | 
| Incidence of adverse events | Safety Observation: Number of participants with adverse events and severe adverse events after drug injection. | up to 14 days post injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution of XTR004 after a single dose IV injection. PET scan acquisition; | Whole-body PET scan obtained at the following time points; at 0-60, 120, 150, 240, and 270 minutes, post injection. | up to 4.5 hours | 
| Plasma and blood radioactivity analysis | Venous blood collection of 6ml at 1.5, 3, 5, 10, 30, 60, 120, 240 and 420 minutes for plasma and blood radioactivity analysis, post injection | up to 7 hours | 
| Urine radioactivity analysis | Urine will be collected up to   7.25 hours to assess for radioactivity, post injection. | up to 7.25 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
coronary artery disease, positron emission tomography, myocardial perfusion imaging, XTR004