To Evaluate the Pharmacokinetics and Safety of TQD3524 for Injection in Renal Impairment Subjects

NCT06522945 | Completed Phase 1

• 1 other identifier: TQD3524-I-02
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open, open-label, parallel, single-dose, phase I clinical study designed to evaluate the pharmacokinetic (PK) profile of TQD3524 injection in patients with renal impairment after a single dose, and to evaluate the urinary excretion of the drug in these patients after a single dose, as well as to evaluate the safety of the drug in these patients after a single dose.

Conditions

Multi-resistant Gram-negative Bacteria Cause Infection

Outcome Measures

Primary Outcomes (9)

• Peak concentration (Cmax)

  Maximum plasma drug concentration

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Area under the concentration-time curve (AUC)

  Area under the plasma concentration-time curve

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Time-to-maximum concentration (Tmax)

  Time-to-maximum concentration

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Plasma half life (t1/2)

  The time it takes for the concentration or amount in the body of that drug to be reduced by exactly one-half

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Total body clearance (CLt)

  Total body clearance of TQD3524

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Renal clearance (CLr)

  Renal clearance of TQD3524

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Apparent volume of distribution (Vd/F)

  Volume of distribution based on the terminal phase

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Terminal elimination rate (λz)

  First-order rate constant associated with the terminal (log-linear) elimination phase

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Mean residence time (MRT)

  The average time that the drug stays in the body

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

Secondary Outcomes (2)

• Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24)

  Before administration, 1.75 , 2 , 2 .5, 3.5, 5 , 7 , 9,12 , 16, 24 hours after administration

• Adverse event rate

  Baseline up to 72 hours

Study Arms (6)

A: Mild Renal Impairment (GFR:60~89 mL/min)

ACTIVE COMPARATOR

A: TQD3524 2.5 mg/kg administered as a 90 minute infusion via infusion pump, single dose

Drug: TQD3524

B: Moderate Renal Impairment (GFR:30~59 mL/min)

ACTIVE COMPARATOR

B: TQD3524 2.5 mg/kg administered as a 90 minute infusion via infusion pump, single dose

Drug: TQD3524

C: Severe Renal Impairment (GFR:15~29 mL/min)

ACTIVE COMPARATOR

C: TQD3524 1.25 mg/kg administered as a 90 minute infusion via infusion pump, single dose

Drug: TQD3524

D: End-stage renal disease (patients undialyzed ) (GFR<15 mL/min)

ACTIVE COMPARATOR

D: TQD3524 1.25 mg/kg administered as a 90 minute infusion via infusion pump, single dose

Drug: TQD3524

E: End-stage renal disease (patients dialyzed) (GFR<15 mL/min)

ACTIVE COMPARATOR

E: TQD3524 1.25 mg/kg administered as a 90 minute infusion via infusion pump, single dose

Drug: TQD3524

F: Normal (GFR≥90mL/min)

ACTIVE COMPARATOR

F: TQD3524 2.5 mg/kg administered as a 90 minute infusion via infusion pump, single dose

Drug: TQD3524

Interventions

TQD3524 DRUG

Polymyxin antibiotics

A: Mild Renal Impairment (GFR:60~89 mL/min)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand the content, process and possible adverse reactions of the trial, be able to complete the study in accordance with the requirements of the trial protocol, and voluntarily sign the informed consent;
• Participants (including their partners) voluntarily used effective contraception within 6 months from screening until the last use of study drug;
• Participants aged 18 \~ 75 ;
• Body mass index (BMI) and 18 or 32 kg/m2 or less, and the male weight 50 kg or greater, female weight 45 kg or more;
• Subjects with moderate to severe renal insufficiency and end-stage renal disease were required to meet the diagnostic criteria for chronic kidney disease;
• Stable renal function: creatinine detection of at least two intervals of 3 days (30 days before the screening test results for the first time acceptable) inside and outside school or in our test result, and two detecting serum creatinine results before and after the fluctuation (calculation formula: (second results - 1)) / 1 time is less than 30%;
• During the screening period, the individual glomerular filtration rate (GFR, mL/min, using the Modification of Diet in Renal Disease (MDRD) formula, based on the results of the second serum creatinine test) was classified as follows: 60≤GFR≤89 mL/min (Group A, mild renal dysfunction, chronic kidney disease stage 2 (CKD2) period), or 30≤GFR≤59 mL/min (Group B, moderate renal dysfunction, chronic kidney disease stage 3 (CKD3) period), or 15≤GFR≤29 mL/min (Group C, severe renal dysfunction, chronic kidney disease stage 4 (CKD4) period), or GFR\<15 mL/min (Group D, end-stage renal disease, not on dialysis; Group E, end-stage renal disease, on dialysis);
• During the screening period, normal vital signs, laboratory tests, physical examination, 12-lead ECG, chest radiographs, and echocardiography results, or abnormal results determined by the investigator to be of no clinical significance, are considered normal.

You may not qualify if:

• All subjects were not eligible for the study if they met any of the following criteria:
• Individuals with an allergy disposition, or those with a history of allergic reactions to polymyxin-type drugs (including polymyxin B, polymyxin sulfate, and polymyxin E monosodium salt);
• Participants who have had any type of treatment or untreated malignant tumor (excluding basal cell carcinoma of the skin) within the past 5 years or at baseline;
• Participants who have had a serious digestive, respiratory, nervous, hematological, endocrine, tumor, immune, psychological, or cardiovascular disease within the past year and are deemed unfit for the study by the investigator;
• Participants who have had a major illness or surgery within the past 4 weeks or plan to undergo surgery during the study period;
• Participants who have donated blood (or lost blood) of at least 400 mL within the past 3 months or have received blood products;
• Participants who have smoked an average of more than 10 cigarettes per day within the past 3 months;
• Participants who have consumed an average of more than 14 units (female subjects) or 21 units (male subjects) of alcohol per week within the past 3 months (1 unit = 285 mL of beer, 25 mL of distilled spirits, or 100 mL of wine);
• Participants who have consumed a special diet (including dragon fruit, mango, grapefruit, and/or xanthine diet, chocolate) and/or consumed excessive tea, coffee, grapefruit/grapefruit juice, and/or caffeine-containing beverages (an average of 8 cups or more per day, 200 mL per cup) within the past 2 weeks;
• Participants who have consumed any alcoholic beverages within 48 hours of receiving the study drug or who have a positive breath alcohol test; 10) Individuals with a history of drug abuse within the past 5 years, or who have used soft drugs (e.g. marijuana) within the past 3 months, or who have used hard drugs within the past year, or who have a positive drug screen at baseline (if urine is available, screen for end-stage renal disease);
• Individuals with positive HIV antibody; positive hepatitis C virus (HCV) antibody or HBsAg positive; positive syphilis treponemal antibody;
• Pregnant or lactating women, and women of childbearing potential with a positive pregnancy test result;
• Individuals who have used strong inhibitors or inducers of liver metabolizing enzymes within the past 14 days;
• Other situations that the investigator considers inappropriate for enrollment.
• Renal impairment subjects were not eligible for the study if they met any of the following criteria:

Sponsors & Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of Shandong First Medical University (Qianfoshan Hospital)

Jinan, Shandong, 250000, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2024
• First Posted: July 26, 2024
• Study Start: July 24, 2024
• Primary Completion: December 18, 2025
• Study Completion: December 18, 2025
• Last Updated: January 9, 2026

Record last verified: 2025-12

Locations

CN (1)