A Study of XTR004 Radiotracer in Healthy Volunteers

Myocardial Ischemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05195879
• Other study ID #: STB-XTR004-101
• Status: Completed
• Phase: Phase 1
• Start date: March 23, 2021
• Est. completion date: July 30, 2021

Study information

• Verified date: January 2022
• Source: Sinotau Pharmaceutical Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: July 30, 2021
• Est. primary completion date: July 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Artery Disease (CAD)
• Coronary Disease
• Ischemia
• Myocardial Ischemia

Intervention

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.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Sinotau Pharmaceutical Group

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Urine radioactivity analysis	Urine will be collected up to ~ 7.25 hours to assess for radioactivity, post injection.	up to 7.25 hours