Single-dose PK study of HRS-4729 in adults with and without kidney impairment

Inclusion Criteria:

1. Provide written informed consent prior to any study-related procedures, and have a full understanding of the study content, procedures, and potential adverse events.
2. Be aged 18 to 65 years (inclusive), of either sex.
3. Have a body mass index (BMI) between 19 and 40 kg/m² (inclusive).
4. Glomerular filtration rate (absolute eGFR) must meet the relevant requirements and criteria specified in the protocol.
5. Have stable renal function.
6. Women of childbearing potential must have been using reliable contraception and have a negative serum pregnancy test at baseline, and must be willing to use highly effective contraceptive measures from the time of signing informed consent until 2 months after the last dose of study drug. Male Participants must be willing not to plan to father a child during the trial and until 2 months after the last dose, and voluntarily take effective contraceptive measures, or have undergone surgical sterilization.
7. Healthy participants: demographic means at screening must match those of the renal impairment groups as follows:

Body weight matched within ±10 kg of the group mean; Age matched within ±10 years of the group mean; Sex ratio matched within ±1 subject. 8.For participants in the renal impairment groups: Participants must have a diagnosis of chronic (\>3 months) and stable (no acute deterioration of renal function within 1 month prior to screening) renal impairment.

Exclusion Criteria:

1. Have a history of significant abnormal gastric emptying, severe gastrointestinal disease, or gastrointestinal surgery (except gastrointestinal polypectomy), as assessed by the investigator to be unsuitable for participation.
2. Have a history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2), or a history of pancreatitis or symptomatic cholelithiasis.
3. Have a history of malignancy in any organ system within the past 5 years, regardless of evidence of local recurrence or metastasis, with the exception of cured localized basal cell carcinoma of the skin, carcinoma in situ of the cervix, and carcinoma in situ of the prostate.
4. Have undergone any surgery within 6 months prior to dosing, or plan to undergo surgery during the study period (excluding gastrointestinal polypectomy).
5. Have participated in any clinical trial of a drug or medical device within 3 months prior to dosing. Participation in a clinical trial is defined as having signed informed consent and having used the investigational product (including placebo) or investigational medical device; or are still within the follow-up period of another clinical study or within 5 half-lives of the investigational drug (whichever is longer).
6. Have had blood loss or blood donation of ≥400 mL within 3 months prior to dosing, or ≥200 mL within 1 month prior to dosing, or have received a blood transfusion within 3 months prior to dosing.
7. Have a known history of severe drug allergy or drug hypersensitivity;
8. Test positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), human immunodeficiency virus (HIV) antibody, or positive for rapid plasma reagin (RPR) test or toluidine red unheated serum test (TRUST) for syphilis.
9. Have a history of drug abuse or substance abuse within 1 year prior to dosing, or test positive on urine multi-drug screening.
10. Are habitual smokers or drinkers and are unable to abstain during the trial; or have a positive alcohol breath test.
11. Have used receptor agonists or inhibitors related to the investigational drug within 2 months prior to screening; Participants who discontinued the above agents due to intolerance more than 2 months prior to screening should also be excluded.
12. Are pregnant or lactating women at the time of screening and baseline visits.
13. Have consumed foods or beverages containing methylxanthines (e.g., tea, coffee, cola, chocolate, energy drinks) or alcohol within 48 hours prior to the first dose of study drug; or have engaged in strenuous exercise within that period.
14. Have a history of needle phobia, syncope with blood or needles, difficulty in blood collection, or intolerance to venipuncture.
15. Have special dietary habits that, in the investigator's opinion, make them unsuitable for participation, or are unable to comply with the dietary requirements during the trial.
16. Have any other condition that, in the investigator's opinion, makes the subject unsuitable for the study, or withdraw voluntarily for personal reasons.
17. For healthy participants:

1）At screening, have systolic blood pressure \<90 mmHg or ≥140 mmHg, diastolic blood pressure \<50 mmHg or ≥90 mmHg, or heart rate \<50 bpm or \>100 bpm. 2）Have a history of significant diseases involving the cardiovascular, hepatic, renal, digestive, psychiatric/neurological, endocrine, respiratory, hematological, or immune systems prior to screening. Have used any medication (including over-the-counter drugs, herbal medicines, and dietary supplements) that, in the investigator's judgment, may affect the study results, within 14 days or 5 half-lives (whichever is longer) prior to dosing. 3）Have clinically significant abnormalities in physical examination, vital signs, laboratory tests (hematology, biochemistry, urinalysis, coagulation, etc.), or 12-lead electrocardiogram (including QTcF) at screening.

18.For participants with renal impairment:

1. Have poorly controlled blood pressure despite pharmacological intervention at screening: systolic blood pressure \<90 mmHg or ≥160 mmHg, diastolic blood pressure \<50 mmHg or ≥100 mmHg, or heart rate \<50 bpm or \>100 bpm.
2. Have obstructive uropathy (e.g., urinary stones, urinary obstruction due to abdominal space-occupying lesions) and/or diseases that may cause renal damage (e.g., renal artery stenosis, acute drug-induced injury, severe infection, hypovolemia).
3. Have a history of severe disease involving the cardiovascular (except for well-controlled hypertension within the past month), respiratory, hepatic, gastrointestinal, endocrine (except for hyperlipidemia, hyperuricemia, and diabetes with stable blood glucose within the past month), hematological, or psychiatric/neurological systems within 1 year prior to screening, as assessed by the investigator to be unsuitable for participation; or have a prior diagnosis of decompensated heart failure (NYHA Class III or IV).
4. Have undergone renal transplantation.
5. Have not been on a stable regimen of therapeutic medications for their renal disease and/or other comorbidities for at least 1 month prior to screening, or have had any new medication added within 1 month prior to screening (excluding temporary or intermittent medications, such as erythropoietin administered once monthly or as-needed diuretics); or have received any drug known to affect renal tubular secretion of creatinine (e.g., cimetidine, trimethoprim, or cibenzoline) within 14 days or 5 half-lives (whichever is longer) prior to dosing.
6. Have any of the following abnormalities in laboratory tests (hematology, biochemistry, urinalysis, coagulation, etc.) or 12-lead ECG at screening:

   1. Hemoglobin \<85 g/L;
   2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3× upper limit of normal (ULN), and total bilirubin (TBIL) ≥1.5× ULN;
   3. Fasting triglycerides (TG) \>5.64 mmol/L (500 mg/dL);
   4. Clinically significant abnormalities in serum amylase or lipase;
   5. QTcF (Fridericia-corrected) \>450 msec in males or \>470 msec in females;
   6. Any other laboratory abnormality that, in the investigator's opinion, may affect subject safety.