Phase Ib Clinical Study on the Safety, Tolerability and Pharmacokinetic Characteristics of GMDTC for Injection After Repeated Administration in People With Excessive Cadmium Levels
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
GMDTC group
The subjects assigned to the GMDTC group will be administered once every morning after eating a standard breakfast on D1-D3 and D8-D10.
干预措施: GMDTC for injection (Drug)
Normal saline group
The subjects assigned to the placebo group will be administered once every morning after eating a standard breakfast on D1-D3 and D8-D10.
干预措施: Normal saline (Other)
结局指标
主要结局
Adverse events
时间窗: 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.
次要结局
- Pharmacokinetic parameters,Tmax(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)
- Pharmacokinetic parameters, Cmax(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)
- Pharmacodynamic parameters, urine cadmium(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)
- Pharmacokinetic parameters, λz(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)
- Pharmacodynamic parameters, blood cadmium(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)
- Pharmacodynamic parameters, 24-hour urine cadmium(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)
- Pharmacodynamic parameters,serum electrolyte and trace element(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)
- Pharmacodynamic parameters, other blood heavy metals(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)
- Pharmacokinetic parameters, t1/2(Evaluated at baseline, during drug infusion, and within 24 hours after drug administration)