Safety Study of GMDTC Injection in Healthy Participants

Phase 1

Completed

• Conditions: Cadmium Exposure
• Interventions: Drug: GMDTC for injection; Other: Normal saline

• Registration Number: NCT05908383
• 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 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.

Study Timeline

• Study Start: 2023-01-30
• Study First Submitted: 2023-05-30
• Study First Submitted QC: 2023-06-09
• Study First Posted: 2023-06-18
• Primary Completion: 2023-06-30
• Study Completion: 2023-07-30
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-29
• Last Update Posted: 2024-01-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 76

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GMDTC for injection	GMDTC for injection	The subjects assigned to the treatment group will receive once medication at 8:00 am on the second day after admission.
Normal saline group	Normal saline	The subjects assigned to the placebo group will receive once medication at 8:00 am on the second day after admission.

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.
DLT	up to 1 weeks	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℃

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.
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, 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, 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.
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
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, 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, 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

Trial Locations

Locations (1)

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