Clinical trial NCT05908383: Safety Study of GMDTC Injection in Healthy Participants
Official title: Phase I Clinical Study on the Safety, Tolerability and Pharmacokinetic Characteristics of a Single Dose of GMDTC Administered to Healthy Subjects for Injection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cadmium Exposure
Keywords: cadmium
Cadmium Poisoning
Therapeutics
Drugs, Investigational
Lead sponsor: Jianersheng (Zhuhai) Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-06-18
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
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 injectable GMDTC in healthy subjects

Detailed description: 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.

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;
* 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)

Primary outcomes:
measure: Adverse events
timeFrame: Up to 30 days
measure: DLT
timeFrame: up to 1 weeks
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: Fang Pei, PhD-c
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Occupational Disease Prevention and Control Institute
name: Xiaobin Deng
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).
citation: Guidelines for the validation of quantitative analysis methods for biological samples in the 2020 edition of the Chinese Pharmacopoeia.