This trial is a randomized, double-blind, single-center, single-dose escalating Phase I clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic characteristics of injectable GMDTC in healthy subjects
The primary objective of this study is to evaluate the safety and tolerability of a single dose of injectable GMDTC in healthy subjects and to determine the maximum tolerated dose (MTD). The secondary objective is to evaluate the pharmacokinetic characteristics of injectable GMDTC after a single dose in healthy subjects and its impact on cadmium levels in the body.The modified Fibonacci method (also known as the Fibonacci dose escalation method) was used for dose escalation, with six predetermined dose groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
76
GMDTC for injection with a specification of 0.5g/vial, 250mg,500mg,850mg,1200mg,1600mg,2000mg, and administered by intravenous infusion. Using 0.9% physiological saline (0.5g will be prepared with 250mL injection solution to achieve a concentration of 2mg/mL). Using an infusion pump at a rate of 4mL/min according to the dosage, and any infusion reactions will be recorded. The injection solution for both the experimental and placebo groups should be prepared by a non-blind investigator independent of the trial.
0.9% physiological saline for injection with a specification of 250ml/bag, and administered by intravenous infusion. Using an infusion pump at a rate of 4mL/min according to the dosage, and any infusion reactions will be recorded. The injection solution for both the experimental and placebo groups should be prepared by a non-blind investigator independent of the trial.
Hunan Occupational Disease Prevention and Control Institute
Changsha, Hunan, China
Adverse events
Adverse events will be evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, V5.0), which includes spontaneously reported adverse events as well as clinically significant changes in vital signs, physical examination, laboratory tests, electrocardiogram, and other examinations conducted during the trial.
Time frame: Up to 30 days
DLT
DLT is defined as the occurrence of any of the following adverse events defined by NCI CTCAE V5.0 after drug administration: 1) grade 3 (severe) toxicity related to the investigational drug, such as events resulting in hospitalization or leading to serious or permanent disability or defect; 2) grade 4 (life-threatening) toxicity or any toxicity deemed by the investigator to be significantly severe; 3) grade 3 neutropenia accompanied by infection or fever of ≥38.5℃
Time frame: up to 1 weeks
Pharmacokinetic parameters,Tmax
Peak time, reflecting the absorption, distribution, metabolism and excretion characteristics of drugs in the body.
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
Pharmacokinetic parameters, Cmax
Peak concentrations, reflecting the absorption, distribution, metabolism and excretion characteristics of drugs in the body.
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
Pharmacokinetic parameters, λz
The apparent terminal elimination rate constant, obtained by taking a half-log linear regression at the elimination phase concentration point, reflecting the absorption, distribution, metabolism and excretion characteristics of drugs in the body.
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
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Pharmacokinetic parameters, t1/2
the apparent terminal elimination half-life, calculated according to the following equation:t1/2= Ln(2)/ λz,reflecting the absorption, distribution, metabolism and excretion characteristics of drugs in the body.
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
Pharmacodynamic parameters, blood cadmium
blood cadmium concentration before and after drug administration
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
Pharmacodynamic parameters, urine cadmium
urine cadmium level before and after drug administration (μmol/mol creatinine)
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
Pharmacodynamic parameters, 24-hour urine cadmium
24-hour urine cadmium excretion before and after drug administration
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
Pharmacodynamic parameters,serum electrolyte and trace element
serum electrolyte and trace element concentrations before and after drug administration
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
Pharmacodynamic parameters, other blood heavy metals
whole blood heavy metal levels before and after drug administration
Time frame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration