Clinical trial NCT06199349: Safety Study of GMDTC Injection in Participants With Excessive Cadmium
Official title: Phase Ib Clinical Study on the Safety, Tolerability and Pharmacokinetic Characteristics of GMDTC for Injection After Repeated Administration in People With Excessive Cadmium Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cadmium Exceeds the Standard
Keywords: cadmium
Cadmium Poisoning
Therapeutics
Drugs, Investigational
GMDTC
Lead sponsor: Jianersheng (Zhuhai) Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: Up to 30 days
Secondary outcomes:
measure: Pharmacokinetic parameters,Tmax
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
measure: Pharmacokinetic parameters, Cmax
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
measure: Pharmacokinetic parameters, λz
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
measure: Pharmacokinetic parameters, t1/2
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
measure: Pharmacodynamic parameters, blood cadmium
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
measure: Pharmacodynamic parameters, urine cadmium
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
measure: Pharmacodynamic parameters, 24-hour urine cadmium
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
measure: Pharmacodynamic parameters,serum electrolyte and trace element
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
measure: Pharmacodynamic parameters, other blood heavy metals
timeFrame: Evaluated at baseline, during drug infusion, and within 24 hours after drug administration
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Occupational Disease Prevention and Control Institute
state: Hunan
Study officials:
affiliation: Hunan Occupational Disease Prevention and Control Institute
name: Yan Lai
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Occupational Disease Prevention and Control Institute
name: Fang Pei, PhD-c
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tang X, Zhu J, Zhong Z, Luo M, Li G, Gong Z, Zhang C, Fei F, Ruan X, Zhou J, Liu G, Li G, Olson J, Ren X. Mobilization and removing of cadmium from kidney by GMDTC utilizing renal glucose reabsorption pathway. Toxicol Appl Pharmacol. 2016 Aug 15;305:143-152. doi: 10.1016/j.taap.2016.06.001. Epub 2016 Jun 6.
citation: Li Guangxian. Study on the efficacy of GMDTC in removing cadmium and its toxic side effects in chronic cadmium-poisoned mice and rats [D]. Guangdong Pharmaceutical University, 2015.
citation: Guidelines for the management of Phase I clinical trials of drugs (trial implementation)