A Study of HRS9531 in Participants With Impaired Kidney Function and Healthy Subjects

Korábbi kezelés

• Had a severe trauma or major surgery within 6 months prior to screening, planned to undergo surgery during the trial period;
• Participants in clinical trials of any drug or medical device in the 3 months prior to screening;
• Blood donation history or blood loss ≥400 mL within 3 month or ≥200 mL within 1 month before screening, or received blood transfusion within 3 months;
• Regularly use known drugs of abuse and/or show positive findings on urinary drug screen that are not otherwise explained by permitted concomitant medications;
• Have an average weekly alcohol intake that exceeds 14 units per week or average daily cigarettes consumption exceeds 5 per day, and are unwilling to stop alcohol or cigarettes consumption 24 hours prior to dosing until discharge from the study or completion of all study procedures (1 unit =12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits);
• The use of alcohol- or caffeine-containing foods or beverages within 72 hours prior to Check-in (Day -1), unless deemed acceptable by the investigator;

Más betegség

• Have any GI disease which impacts gastric emptying (eg, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy);
• Have a personal or family history of medullary thyroid carcinoma or have multiple endocrine neoplasia syndrome type 2; Have a history or presence of pancreatitis;
• Allergic constitution includes severe drug allergy or history of drug allergy;
• Hepatitis B surface antigen (HBsAg), HIV antibody detection, hepatitis C virus antibody (HCVAb), treponema pallidum specific antibody detection, positive;
• History of Vasovagal Syncope; Do not have venous access sufficient to allow blood sampling as per the protocol；

Laborértékek

• History use of GLP-1R（glucagon-like peptide-1 receptor） agonist, GLP-1R/GCGR（glucagon receptor）agonist, GIPR（glucose-dependent insulinotropic polypeptide receptor/GLP-1R agonist or GIPR/GLP-1R/GCGR agonist within 2 months prior to screening;
• Healthy Participants:
  • Systolic blood pressure <90 mmHg or ≥140 mmHg; Diastolic blood pressure <50 mmHg 或≥90 mmHg; Heart Rate < 50 beats/min or >100 beats/min;
  • Have a significant history or presence of cardiovascular (eg, myocardial infarction, cerebrovascular accident, etc. within the past 6 months), respiratory, hepatic, renal, GI, endocrine (except T2DM), haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data;
  • Use of medications determined to be unsuitable by the investigator (including over-the-counter medication, prescription medication and herbal preparations) within the 14 days prior to screening;
  • Have clinical laboratory test results outside normal reference range for the population or investigator site and judged to be clinically significant by the investigator;
• Participants with Renal Impairment：
  • Systolic blood pressure <90 mmHg or≥160 mmHg; Diastolic blood pressure <50 mmHg 或 ≥100 mmHg; Heart Rate < 50 beats/min or >100 beats/min;
  • Have a significant history or presence of cardiovascular (eg, myocardial infarction, cerebrovascular accident, decompensated heart failure (NYHA classification III or IV), etc. within the past 6 months), respiratory, hepatic, renal (obstructive urinary tract disease, except CKD), GI, endocrine (except T2DM), haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data;
  • History of Kidney Transplant;
  • Subjects started new over-the-counter or prescription medications (eg, antihypertensive agents, aspirin, lipid-lowering agents) for treatment of concurrent medical conditions or on their treatment regimen for less than 1 month;
  • Have following clinically relevant abnormal laboratory test results:
  • Hemoglobin <85 grams per liter (g/L);
  • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3× the upper limit of normal (ULN) or total bilirubin (TBL) >1.5× ULN;
  • Serum triglyceride > 5.64 mmol/L（500 mg/dl）;
  • Clinical relevant elevation in serum amylase or lipase；
  • QTcF > 450 msec;
  • Other abnormal lab results, as determined by the investigator.

Egyéb

• Breast-feeding women;
• The need to follow a special diet and unable to follow the diet requirement of protocol;
• The investigator considers that the subject has any other factors that would make it inappropriate to participate in this study

• Ability to understand the trial procedures and possible adverse events, be able and willing to provide a written informed consent;
• Age 18-65 years on the date of signing informed consent (inclusive);
• Body mass index (BMI) within the range of 19.0-40.0 kg/m2 (inclusive);
• Renal function, assessed by estimated glomerular filtration rate at screening (eGFR):
  • Normal renal function: 90-129 mL/min (inclusive);
  • Mild impairment: 60-89 mL/min (inclusive);
  • Moderate impairment: 30-59 mL/min (inclusive);
  • Severe impairment: 15-29 mL/min (inclusive);
• Females of childbearing potential should have negative baseline blood pregnancy test, and must use highly effective contraception from signing the informed consent form to 2 months after the last dose of trial drug; Male subjects must agree to either remain abstinent or use highly effective contraceptive measures during the trial and 2 months after last dose of the trial drug, or have been surgically sterilized;
• Stable renal function, assessed by two eGFR during screening (apart at least 3 days);
• Diagnosed as stable, chronic renal disease for at least 3 months.