Single 3 mg Azvudine safety and blood-level test for adults with mild-to-moderate kidney decline and healthy adults

A Non-randomized, Open, Parallel, Single-dose Pharmacokinetics and Safety Study of Azvudine Tablets in Subjects With Mild-To-Moderate GFR Decline in Renal Insufficiency and in Healthy Subjects

This trial gives a single 3 mg dose of Azvudine to adults with mild-to-moderate kidney function decline and to healthy adults to test how the body handles the drug and whether it is safe.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Henan Genuine Biotech Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07001436 on ClinicalTrials.gov

What this trial studies

This is a non-randomized, open-label, parallel, single-dose adaptive pharmacokinetic and safety study comparing adults with mild-to-moderate renal insufficiency to healthy adults. Participants receive a single oral 3 mg dose (three 1 mg tablets) of Azvudine on an empty stomach with timed biological sample collection for drug concentration measurements and safety monitoring. The trial enrolls adults 18–70 years old with BMI 18.0–30.0 and includes contraception requirements for participants of reproductive potential. The main outcomes are blood levels of Azvudine over time and collection of adverse event and tolerability data.

Who should consider this trial

Good fit: Adults aged 18–70 with mild-to-moderate decline in kidney function (renal insufficiency) or healthy adults who meet BMI and weight criteria, agree to contraception rules if applicable, and can attend the Beijing study site are ideal candidates.

Not a fit: People with severe renal failure or on dialysis, children, pregnant or breastfeeding individuals, and those unable to meet the weight/BMI or contraception requirements are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could guide safer dosing recommendations for people with reduced kidney function and help avoid dosing errors.

How similar studies have performed: Single-dose pharmacokinetic studies in renal impairment are a standard approach and Azvudine PK has been studied in healthy subjects, but published data specifically in patients with renal insufficiency are limited.

Eligibility criteria

Inclusion Criteria:

(一) Renal insufficiency study participants and healthy study participants:

1. Age ≥ 18 years old and ≤ 70 years old, regardless of gender;
2. Body mass index (BMI) within the range of 18.0-30.0 (including the critical value) (BMI = weight (kg) / height 2 (m2)), the weight of men should be ≥ 50.0kg, and the weight of women should be ≥ 45.0kg;
3. Females of childbearing potential must have taken reliable and highly effective contraceptive measures and have a negative baseline blood pregnancy test at screening, and are willing to use appropriate and efficient methods of contraception after signing the informed consent form until 3 months after the last dose of the test drug; Male study participants who are willing to do so for the duration of the trial and for 3 months after the last dose of the trial drug Have no plans to have children and voluntarily use highly effective contraception, or have been surgically sterilized;
4. Understand and sign the informed consent form.

(二) Health study participants (in addition to the above criteria, they should also meet):

1. The health condition is judged by the investigator to be good, and the results of vital signs, physical examination, electrocardiogram, and laboratory examination are normal or abnormal, and there is no clinical significance;
2. Those who have not taken any prescription drugs, over-the-counter drugs, Chinese herbal medicines, or health care products within 14 days before screening;
3. Meet the classification standard of glomerular filtration rate of 90≤GFR\<130 ml/min;
4. Study participants with mild or moderate decline in GFR were matched with the following demographic characteristics: age (mean ± 10 years), weight (mean ±10kg), and gender (±1 cases).

(三) Renal insufficiency study participants (in addition to the above criteria, they should also meet):

1. Stable renal function status: the existing renal function impairment is required to last for more than 3 months, and the GFR results of two tests (with an interval of 72 hours or more) during the screening period are within the same grade and the difference between the two tests is not more than 25%;
2. No clinically significant abnormalities were found in the pre-test medical history, vital signs, physical examination, laboratory test items (except ALT and AST, total bilirubin, and direct bilirubin) and test-related examinations and were judged by the clinical research physician to be eligible for enrollment (except for abnormalities related to renal impairment);
3. The drug being taken by the study participant with renal insufficiency, which should not affect the absorption, distribution, metabolism or excretion of the study drug, and has been taken at a stable dose for at least 4 consecutive weeks before giving the study drug, and agrees to continue treatment during the study period;
4. Two weeks before administration and during the test, Chinese patent medicines, traditional Chinese medicine decoctions, ethnic medicines, SGLT-2i, MRA drugs and benzbromarone are prohibited;
5. During the screening period, it is necessary to meet: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) all need to \< 1.5 upper limit of normal (ULN)
6. Participants in the study of renal insufficiency of all grades met the grading criteria for glomerular filtration rate (GFR was taken as the average of the two tests during the screening period): Mild decrease in GFR: 60≤ GFR≤89 ml/min; Moderate decrease in GFR: 30≤GFR ≤59 ml/min.

Exclusion Criteria:

(一) Renal insufficiency and health research participants:

1. Allergies, especially those who are allergic to any of the ingredients in this product and excipients;
2. Those who have undergone gastrointestinal resection in the past, or suffer from digestive diseases that will affect the absorption, distribution, metabolism and excretion of drugs;
3. Those who have a history of drug abuse within 12 months before screening or those who have tested positive for addictive substances before enrollment;
4. Those with fever or infectious diseases at the time of screening;
5. Those who have participated in other clinical trials within 3 months before screening;
6. Those who have a history of smoking addiction within 12 months before screening (the average number of cigarettes per day ≥5);
7. Those who have a history of alcohol abuse within 12 months before screening (drinking ≥ 14 units of alcohol per week: 1 unit = 285mL of beer, or 25mL of spirits, or 150mL of wine) or positive alcohol breath test (test value \>0mg/100mL) before enrollment;
8. Those who have lost blood or donated 200mL of blood ≥ within 8 weeks before screening;
9. Hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, treponema pallidum antibody or rapid plasma reagin ring card test (RPR) test results are positive.
10. Pregnant and lactating women;
11. Those who cannot tolerate vascular puncture blood collection and/or have a history of blood sickness, needle fainting and/or poor blood collection vascular conditions;
12. Those who have been vaccinated within 3 months before screening, or plan to be vaccinated during the trial;
13. Those who are not considered suitable to enter this trial by the investigator.

(二) Renal insufficiency study participants (except for the above criteria):

1. Have undergone kidney transplantation;
2. Systolic blood pressure outside the range of 90 \~ 160mmHg, diastolic blood pressure outside the range of 50 \~ 100mmHg, or heart rate outside the range of 50 \~ 120bpm;
3. Frequent occurrence of hypoglycemia and exclusion of drug factors within 3 months prior to screening;
4. Albumin\<30g/L;
5. Hemoglobin value\<9 g/dL;
6. Those who have a history of uncontrolled or unstable serious diseases of cardiovascular, liver, pulmonary, digestive tract, nerves, autoimmune, metabolic and musculoskeletal systems, hematopoietic systems and other systems, or those whose diseases are active.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Jishuitan Hospital — Beijing, Beijing Municipality, China (Recruiting)

Conditions Renal Insufficiency; Azvudine