Safety Study of GMDTC Injection in Participants With Excessive Cadmium

Phase 1

Completed

• Conditions: Cadmium Exceeds the Standard
• Interventions: Drug: GMDTC for injection; Other: Normal saline

• Registration Number: NCT06199349
• Lead Sponsor: Jianersheng (Zhuhai) Pharmaceutical Technology Co., Ltd.

Brief Summary

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 GMDTC for injection after repeated administration in people with excessive cadmium levels.

Detailed Description

The primary objective of this study isto evaluate the safety and tolerability of injectable GMDTC for repeated administration in people with excessive cadmium. The secondary objective is to evaluate the pharmacokinetic and pharmacodynamic characteristics of GMDTC for injection in people with excessive cadmium levels after multiple administrations, and to explore the most effective dose. Based on the results of the single-dose study, three dose groups were designed, including a low-dose group, a medium-dose group, and a high-dose group.

Study Timeline

• Study First Submitted: 2023-12-29
• Study First Submitted QC: 2023-12-29
• Study Start: 2024-01-08
• Study First Posted: 2024-01-10
• Primary Completion: 2024-10-21
• Study Completion: 2024-12-05
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-19
• Last Update Posted: 2025-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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;
• Urinary cadmium >5 μmol/mol creatinine for 2 consecutive days during the screening period (creatinine content is ≥0.3 μg/L and ≤3 μg/L).
• Subjects must voluntarily sign a written informed consent form.

Exclusion Criteria

• Those who are currently suffering from any clinically serious disease and the researcher determines that there are safety risks in participating in this clinical trial;
• Those with eGFR<30 mL/min/1.73 m2 during screening (eGFR calculated using the Cockcroft-Gault formula: eGFR (mL/min/1.73 m2) =*(140-age) *weight (kg)/ [0.818*Cr (umol/L)] *0.85 (female));
• Those who have a history of allergies to 3 or more substances, or are allergic to any ingredients in this product；
• Those who have undergone surgical procedures within 4 weeks before screening or plan to undergo surgical procedures that affect pharmacokinetics and safety determination during the study period；
• Those who have taken any drugs or health care products that may interact with the experimental drugs within 14 days before screening (such as SGLT2 inhibitors such as dapagliflozin, canagliflozin, empagliflozin, empagliflozin, canagliflozin, etc.) Gliflozin, Henggliflozin, Ipagliflozin, Rupagliflozin, Togliflozin, and the natural compound phlorizin, etc.; GLUT2 inhibitors such as cytochalasin B, phloretin, Huoxiang Zhengqi Powder, and Mignonette herbalin and isoorientin, etc.);
• Those who have used any clinical trial drugs or enrolled in any drug/medical device clinical trials within 3 months before screening;
• Those who donated blood or suffered massive blood loss (≥200 mL, excluding female menstrual blood loss), received blood transfusions or used blood products within 3 months before screening;
• 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;
• Alcoholics or regular drinkers within 6 months before screening, that is, drinking more than 14 units of alcohol per week (1 unit ≈ 200 mL of beer with an alcohol content of 5% or 25 mL of spirits with an alcohol content of 40%- or 85-mL wine with an alcohol content of 12%) or who cannot stop using any alcohol-containing products during the trial;
• 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;
• Laboratory tests must meet one or more of the following during screening: white blood cell count<3.0×109/L, neutrophil count <1.5×109/L, red blood cell count <3.0×1012/L, hemoglobin<100 g/L , platelet count <1 × LLN, total bilirubin > 2 × ULN, alanine aminotransferase > 2 × ULN, aspartate aminotransferase >2 × ULN；
• The subjects may not be able to complete the study due to other reasons or the researchers believe that they should not be included.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GMDTC group	GMDTC for injection	The subjects assigned to the GMDTC group will be administered once every morning after eating a standard breakfast on D1-D3 and D8-D10.
Normal saline group	Normal saline	The subjects assigned to the placebo group will be administered once every morning after eating a standard breakfast on D1-D3 and D8-D10.

Primary Outcome Measures

Name	Time	Method
Adverse events	Up to 30 days	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic parameters,Tmax	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	Peak time, reflecting the absorption, distribution, metabolism and excretion characteristics of drugs in the body.
Pharmacokinetic parameters, Cmax	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	Peak concentrations, reflecting the absorption, distribution, metabolism and excretion characteristics of drugs in the body.
Pharmacodynamic parameters, urine cadmium	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	urine cadmium level before and after drug administration (μmol/mol creatinine)
Pharmacokinetic parameters, λz	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	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.
Pharmacodynamic parameters, blood cadmium	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	blood cadmium concentration before and after drug administration
Pharmacodynamic parameters, 24-hour urine cadmium	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	24-hour urine cadmium excretion before and after drug administration
Pharmacodynamic parameters,serum electrolyte and trace element	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	serum electrolyte and trace element concentrations before and after drug administration
Pharmacodynamic parameters, other blood heavy metals	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	whole blood heavy metal levels before and after drug administration
Pharmacokinetic parameters, t1/2	Evaluated at baseline, during drug infusion, and within 24 hours after drug administration	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.

Trial Locations

Locations (1)

Hunan Occupational Disease Prevention and Control Institute; 🇨🇳 Changsha, Hunan, China