A Study of XTR004 Radiotracer in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Ischemia; Coronary Artery Disease (CAD)
• Intervention / Treatment: Diagnostic test: XTR004

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Chinese men and women are included age between 18-40 years
2. Normal vital signs and physical examination
3. No clinical abnormalities in ECG, EEG, and echocardiogram
4. No past history of cardiovascular, cerebrovascular, or gastrointestinal diseases
5. Normal or no clinical significance abnormalities in laboratory tests
6. No any other major or chronic illness
7. No presence of drug use
8. Females adopt effective medically approved contraceptive methods to prevent pregnancy for at least 6 months before the study and after the study
9. Voluntarily agree and signed written consent

Exclusion Criteria:

1. Previous history of cardiovascular diseases
2. A history of or physical or radiographic manifestations of any previous brain disease
3. Any previous major disease or unstable condition
4. Subjects who cannot complete XTR004 imaging as required
5. Positive HIV, hepatitis C or Treponema pallidum antibody and hepatitis B surface antigen detection
6. A history of coagulation or coagulation disorder
7. A history of liver or gastrointestinal disease or other conditions that interfere with drug absorption, distribution, excretion or metabolism as determined by the investigator
8. Previous history of cancer
9. High risk of drug allergic reaction
10. A history of alcohol or drug abuse/dependence
11. 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
12. Scheduled surgery or other invasive interventions within one week before drug injection
13. Subjects use any drug or treatment that may interfere with the experimental data or cause serious side effects, as determined by the investigator
14. Pregnant or lactating women
15. Admitted to hospital due to illness during screening period Other conditions that investigators consider inappropriate to participate in a trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XTR004; Single dose 6.0-8.0 mCi intravenous injection of XTR004 and investigation of XTR004 (MPI radiotracer).	Diagnostic test: XTR004; 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.

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

Collaborators and Investigators

• Sponsor: Sinotau Pharmaceutical Group

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 19, 2022

Study Record Updates

• Last Update Posted (Actual): February 7, 2022
• Last Update Submitted That Met QC Criteria: January 23, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: coronary artery disease; positron emission tomography; myocardial perfusion imaging; XTR004
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ischemia
• Other Study ID Numbers: STB-XTR004-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No