Cadmium Exceeds the Standard
Conditions
Keywords
cadmium, Cadmium Poisoning, Therapeutics, Drugs, Investigational, GMDTC
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.
Interventions
GMDTC for injection with a specification of 0.5g/vial, 500mg,1000mg,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.
OTHERNormal saline
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
Sponsors
Jianersheng (Zhuhai) Pharmaceutical Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This clinical study is a double-blind study, in which participants such as clinical researchers, project managers, and project monitors are unaware of the random coding and drug administration groups of the subjects. Non-blind monitoring during the clinical study will be conducted by non-blind monitors. In addition, drug preparation will be carried out by non-blind researchers independent of this study. Analysis and testing personnel will also adopt blind analysis.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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 |
| 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. |
| 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 |
| 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) |
Countries
China
Outcome results
None listed