Safety Study of GMDTC Injection in Healthy Participants

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Phase I Clinical Study on the Safety, Tolerability and Pharmacokinetic Characteristics of a Single Dose of GMDTC Administered to Healthy Subjects for Injection

Conditions
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Cadmium Exposure

Intervention / Treatment
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* Drug: GMDTC for injection
* Other: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years, both male and female are eligible; Male subjects must weigh at least 50.0 kg and female subjects must weigh at least 45.0 kg, with a body mass index (BMI) between 19 and 26 kg/m2, including the critical value; Subjects must voluntarily sign a written informed consent form. Exclusion Criteria: past or current clinical significant diseases that affect the circulatory, endocrine, nervous, digestive, respiratory, renal, hematological, immunological, psychiatric, and metabolic systems or any other disease or symptom that may interfere with the study results; eGFR<90 mL/min/l.73 m2 during screening (eGFR calculated using the Cockcroft-Gault formula: eGFR (mL/min/1.73 m2) =*(140-age)weight (kg)/[0.818Cr (umol/L)]*0.85 (female)); urine creatinine (Cr) > 5 umol/mol for two consecutive days during screening (with a creatinine concentration of≥0.3 g/L and ≤3 ug/L); a history of allergy to drugs, food, or other substances, especially to the components of the study drug; undergone or planned surgery that affects drug metabolism and safety assessment within 4 weeks before screening; use of any medication or health supplements (including Chinese herbal medicine) within 14 days before screening; participated in any clinical trial and used any investigational drug within three months before screening; blood donation or significant blood loss (≥200 mL, excludingmenstrual bleeding in women) within 3 months before screening, blood transfusion, or use of blood products; inability to tolerate venipuncture and/or history of fainting or needle phobia; pregnant or lactating women, and subjects who cannot adopt effective non-drug contraceptive measures during the study period; unable to adopt contraceptive measures within 6 months after the end of the study; have special dietary requirements and cannot adhere to a uniform diet; daily consumption of excessive tea, coffee, and/or caffeine-containing beverages (more than 8 cups, 1 cup - 250 mL); unable to stop using any tobacco products during the study period; alcoholics or frequent drinkers within 6 months before screening, i.e., drinking more than 14 units of alcohol per week (1 unit - 360.5 mL of beer or 45 mL of 40% alcohol or 150 mL of wine) or unable to stop using any alcohol-containing products during the study period; drug abusers or those who used soft drugs (such as marijuana) within 3 months before screening or used hard drugs (such as cocaine, benzoyl peroxide, etc.) within 1 year before screening; clinically significant abnormalities in vital signs, physical examination, electrocardiogram, electroencephalogram, cardiac ultrasound, abdominal ultrasound, chest CT, ophthalmic examination, or laboratory tests (as judged by the clinical research physician)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GMDTC for injection<br>The subjects assigned to the treatment group will receive once medication at 8:00 am on the second day after admission. | Drug: GMDTC for injection<br>* 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.<br>* Other names: GMDTC Group;|
| Placebo Comparator: Normal saline group<br>The subjects assigned to the placebo group will receive once medication at 8:00 am on the second day after admission. | Other: Normal saline<br>* 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.<br>* Other names: Normal saline Group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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℃ | up to 1 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters,Tmax | Peak time, reflecting the absorption, distribution, metabolism and excretion characteristics of drugs in the body. | 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. | 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. | Evaluated at baseline, during drug infusion, and within 24 hours after drug administration | 
| 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. | 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 | 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) | 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 | 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 | 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 | Evaluated at baseline, during drug infusion, and within 24 hours after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cadmium, Cadmium Poisoning, Therapeutics, Drugs, Investigational