The Safety and Efficacy of GMDTC for Injection in Subjects With Elevated Cadmium Levels

Official title

Phase IIa, Randomized, Double-Blind, Placebo-Controlled, Single-Center Clinical Study to Evaluate the Safety and Efficacy of GMDTC for Injection in Subjects With Elevated Cadmium Levels

Overview

This is a randomized, double-blind, placebo-controlled, single-center Phase IIa clinical study.

Detailed description

The primary objective of this study is to evaluate the pharmacodynamic characteristics of GMDTC for Injection in subjects with elevated cadmium levels after administration, while the secondary objectives are to assess the safety, tolerability and pharmacokinetic profile of GMDTC for Injection following multiple-dose administration in the same population; based on the results from Phase I single- and multiple-dose studies, the initial dose group in this trial is set at 2000 mg with a concentration of 4 mg/mL, where the first 4 participants (including 3 in the treatment group and 1 in the placebo group) will be enrolled first, and subsequent participants in the same dose group can only continue enrollment after investigators complete the 72-hour post-dose safety and tolerability assessments and confirm favorable results, with the SMC meeting to determine subsequent study plans including but not limited to dose escalation, concentration adjustment or increased treatment duration after completion of observation for each dose group.

Interventions

• Drug GMDTC for injection
  GMDTC for Injection with a specification of 0.5g/vial, and administered by intravenous infusion. According to the drug preparation SOP , Using 0.9% physiological saline to achieve the required concentration for each dose group (e.g., The initial dose group: 2 g reconstituted in 500 mL, with each 1 g reconstituted in 250 mL, resulting in a 4 mg/mL concentration.). All infusion-related reactions must be documented. Drug preparation must be performed by an non-blind investigator independent of the
• Other 0.9% Sodium Chloride Injection(0.9% NaCl)
  0.9% Sodium Chloride Injection with a specification of 250mL/bag, and administered by intravenous infusion. The infusion should be strictly adhering to the assigned dosage. All infusion-related reactions must be documented. Drug preparation must be performed by an non-blind investigator independent of the study to maintain blinding integrity for other study personnel.

Primary outcome measures

• Pharmacodynamic Parameters , 24-hour urinary cadmium [Time frame: Evaluated at pre-dose (Day-1) and post-dose (Day1-Day6, Day8-Day13)]

Secondary outcome measures (12)

• Adverse Events (AEs) [Time frame: Within 30 days after the last dose administration]
• Pharmacodynamic Parameters , Urinary Cadmium and Lead Levels [Time frame: Evaluated at pre-dose (Day1) and post-dose (Day6, Day8, Day13, Day15)]
• Pharmacodynamic Parameters , 24-Hour Urinary Lead and Copper [Time frame: Evaluated at pre-dose (Day-1) and post-dose (Day1-Day6, Day8-Day13)]
• Pharmacodynamic Parameters , Blood Heavy Metal/Metalloid Levels(Pb, As, Hg, Cr, Mn) [Time frame: Evaluated at pre-dose (Day1) and post-dose (Day6, Day8, Day13)]
• Pharmacodynamic Parameters , Blood Heavy Metal/Metalloid Levels(Cu, Zn) [Time frame: Evaluated at pre-dose (Day1) and post-dose (Day6, Day8, Day13)]
• Pharmacodynamic Parameters , Renal Function Biomarker Levels(Creatinine-corrected urinary β2-MG, Creatinine-corrected urinary URBP) [Time frame: Evaluated at pre-dose (Day1) and post-dose (Day6, Day8, Day13, Day15)]
• Pharmacodynamic Parameters , Renal Function Biomarker Levels(β2-MG, URBP) [Time frame: Evaluated at pre-dose (Day1) and post-dose (Day6, Day8, Day13, Day15)]
• Pharmacodynamic Parameters , Renal Function Biomarker Levels(α1-MG) [Time frame: Evaluated at pre-dose (Day1) and post-dose (Day6, Day8, Day13, Day15)]
• Pharmacodynamic Parameters , Renal Function Biomarker Levels(NAG) [Time frame: Evaluated at pre-dose (Day1) and post-dose (Day6, Day8, Day13, Day15)]
• Pharmacodynamic Parameters, Bone Metabolism Biomarker Levels(PTH) [Time frame: Evaluated at Pre-dose (Screening Period) and post-dose (Day6, Day13)]
• Pharmacodynamic Parameters, Bone Metabolism Biomarker Levels(25(OH)D, P1NP, CTX) [Time frame: Evaluated at Pre-dose (Screening Period) and post-dose (Day6, Day13)]
• Pharmacodynamic Parameters, Bone Metabolism Biomarker Levels(ALP) [Time frame: Evaluated at Pre-dose (Screening Period) and post-dose (Day6, Day13)]

Eligibility criteria

Inclusion criteria

Study participants must meet all of the following criteria to be enrolled in this trial:

• Voluntarily sign the informed consent form, aged between 18 and 70 years (inclusive), regardless of gender;
• Single morning urine cadmium >5 μg/g creatinine (with creatinine concentration ≥0.3 g/L and ≤3 g/L);
• eGFR ≥30 mL/min/1.73 m² (calculated using the CKD-EPI formula).

Exclusion criteria

Participants who meet any of the following criteria will be excluded from this study:

• Currently suffering from any clinically significant disease that, in the investigator's judgment, poses a safety risk for participation in this clinical trial;
• Patients with a history of kidney disease requiring hemodialysis;
• Patients with a history of severe infusion-related allergic reactions, known allergies to three or more substances, or known hypersensitivity to any component of this product (e.g., disodium edetate, mannitol);
• Previous diagnosis of diabetes with poorly controlled blood glucose;
• History of conditions predisposing to hypokalemia (e.g., periodic hypokalemia, primary aldosteronism);
• High-risk uncontrolled arrhythmia within the past 6 months, including:

1\) Resting atrial tachycardia with heart rate >100 bpm, 2) Significant ventricular arrhythmia (e.g., ventricular tachycardia), 3) High-grade atrioventricular block (e.g., Mobitz type II second-degree or third-degree AV block), 4) NYHA Class IV heart failure, 5) Left ventricular ejection fraction (LVEF) <50%; 7.Prolonged QT/QTc interval at screening/baseline (QTc: >450 ms in males, >470 ms in females) or known family history of long QT syndrome; 8. Use of any medication or supplement (e.g., SGLT2 inhibitors like dapagliflozin, canagliflozin, empagliflozin, etc.; GLUT2 inhibitors like cytochalasin B, phloretin, etc.) within 14 days prior to screening that may interact with the investigational drug; 9. Participation in any other clinical trial involving investigational drugs or medical devices within 3 months prior to screening; 10. Major surgery within 4 weeks before screening or planned surgery during the trial that may affect drug metabolism or safety assessment; 11. Blood donation or significant blood loss (≥200 mL, excluding menstrual bleeding), transfusion, or use of blood products within 1 month prior to screening; 12. Intolerance to venipuncture and/or history of syncope due to blood or needle exposure; 13. Pregnant or lactating women, or participants unwilling to use effective non-pharmacological contraception during the trial; 14. Inability to use contraception for 6 months after trial completion; 15.Inability to comply with dietary restrictions or nutritional guidelines; 16.Alcohol abuse or regular alcohol consumption (>14 units/week; 1 unit ≈ 200 mL beer \[5%\], 25 mL spirits \[40%\], or 85 mL wine \[12%\]) within 6 months before screening, or unwillingness to abstain from alcohol during the trial; 17. Participants with unstable psychiatric disorders, in the investigator's opinion, who cannot cooperate with the study; 18. Any other condition deemed by the investigator to compromise study compliance or safety.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment — Guangzhou

Publications

• 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. PMID 27282297

Identifiers

NCT: NCT07057414 · GuangdongPharm IIa

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗