Investigation of Pharmacokinetics, Safety of HSK31858 in Subjects With Renal Impairment

Korábbi kezelés

• Those who have received kidney transplants

Más betegség

• Those with acute kidney injury or acute renal failure; Those with urinary incontinence or anuria;

Laborértékek

• 1) Those who are known to be allergic to any component of the investigational drug or preparation, or those with an allergic constitution (such as being allergic to two or more drugs, foods or pollen, etc.);
  • Those who have special dietary requirements and cannot accept a uniform diet; Or those who have difficulty swallowing;
  • Previously diagnosed as a malignant tumor (excluding radical resection of cutaneous basal cell carcinoma, papillary thyroid carcinoma, cutaneous squamous cell carcinoma or cervical cancer in situ);
  • Participants previously diagnosed with periodontitis or/and palmoplantar hyperkeratosis, and with the following conditions at the time of screening: Participants currently showing signs of gingivitis/periodontitis; or Participants with a history of hyperkeratosis or erythema on the palm or sole of the foot;
  • There are obvious factors or gastrointestinal diseases that significantly affect the absorption of oral medications, such as inability to take oral medications or obvious nausea and vomiting, malabsorption, external biliary drainage, gastrointestinal resection, etc.
  • Those who test positive for any one of the following indicators during the screening period: hepatitis B virus surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or Treponema pallidum antibody;
  • Those with ALT and/or AST > 1.5×ULN, or total bilirubin > 1.5×ULN during screening; However, those who are assessed by the researchers as eligible to continue the experiment are excluded.
  • The QTcF interval during the screening period (calculated by the formula QTcF = QT/RR0.33) was greater than 450ms for men and 470ms for women, or those whose abnormalities were clinically significant as determined by the investigators and were deemed unsuitable for this trial by the investigators.
  • The average daily smoking (or use of an equivalent amount of nicotine-containing products) in the three months prior to screening was more than five cigarettes, or smoking could not be prohibited during the trial period;
  • Those who have a history of alcohol abuse within the three months prior to screening, that is, those who consume more than 14 units of alcohol per week (1 unit =360mL of beer or 45mL of 40% alcohol spirits or 150 ml of wine), or those who cannot abt alcohol during the test period, or those with a positive breath test for alcohol;
  • Those who have consumed excessive amounts of tea, coffee or caffeinated beverages (an average of more than 4 cups per day, 1 cup =250mL) within the three months prior to screening; Or those who have consumed tea or any food or beverage containing caffeine (such as coffee, chocolate, etc.) within 48 hours before the first administration; Or disagree to stop taking tea, coffee or foods or beverages containing caffeine during the trial period;
  • Those who have consumed a large amount of beverages or foods rich in grapefruit (such as grapefruit, grapefruit juice, grapefruit jam, etc.) within 14 days before screening; Or those who have consumed any beverage or food rich in grapefruit (i.e. grapefruit) within 48 hours before the first administration; Or those who do not agree to stop drinking any beverages or foods rich in grapefruit (i.e. grapefruit) during the trial period;
  • Those with a history of drug abuse, drug abuse or drug dependence, or with a positive screening result for drug abuse;
  • Those who have donated blood or lost blood of ≥400mL within the 3 months prior to screening (excluding menstrual blood loss in women) or donated blood during the planned study period;
  • Those who have used any strong suppressor or strong inducer of CYP3A within 28 days before screening or within 5 half-lives of the drug (whichever is longer);
  • Those who have taken any prescription drugs, over-the-counter drugs, Chinese herbal medicines or health supplements within 14 days prior to the administration of the investigational drug or within 5 half-lives of the drug (whichever is longer) (only participants with normal renal function, excluding contraceptives);
  • Those who have participated in any clinical trial of a drug or medical device within 90 days prior to screening, or are still within the follow-up period of a certain clinical trial or within 5 half-lives of the investigational drug before screening (whichever is longer);
  • Those who have received live vaccines (excluding influenza vaccines) within one month prior to screening or plan to receive attenuated live vaccines during the trial period;
  • Those who have had infections using systemic anti-infective drugs (such as respiratory or central nervous system infections, etc.), severe trauma, or major surgical operations within two weeks prior to screening;
  • Those who are expected to have a tendency towards surgery or hospitalization other than those required by the trial during the trial period;
  • Those with a history of fainting at the sight of needles or blood, those who have difficulty in blood collection or cannot tolerate venipuncture blood collection, or those whose physical condition cannot tolerate blood collection;
  • Researchers determine that there are tattoos or scars on any part of the skin that affect the safety assessment.
  • Pregnant or lactating women; Or those with positive results in pregnancy tests;
  • Participants who the researchers consider to have poor compliance or other factors that make them unsuitable for this trial;
  • For patients with renal insufficiency, the following exclusion criteria should also be added:
• Those who have received any drugs known to affect serum creatinine (such as glycopeptide antibiotics, aminoglycoside antibiotics, etc.) within 28 days before screening or within 5 half-lives of the drugs (whichever is longer), or those who are expected to take the above drugs during the trial period;
• Hemoglobin during screening 90g/L; Triglycerides during screening \> 2.3 mmol/L;
• For patients with chronic diseases such as hypertension, diabetes, and hyperuricemia, who remain unstable after drug treatment (blood pressure ≥160/100 MMHG, glycated hemoglobin > 9.0%, blood uric acid level ≥480 μmol/L), and whom the researchers consider to be at risk for inclusion in this trial; Those who have experienced acute cardiovascular and cerebrovascular diseases (such as acute myocardial infarction, cerebral infarction, etc.) within half a year;

Egyéb

• Those who need renal dialysis during the study period or have undergone dialysis (including peritoneal dialysis) within the past year;

• 1) Participants can understand the nature, purpose, procedures, possible risks and adverse reactions of this trial, and complete the trial as required. Voluntarily participate in clinical trials and sign the informed consent form before the trial commences;
  • Male or female participants aged 18 to 70 years old on the day of signing the informed consent form (including the cut-off value);
  • When screening, the weight of men should be ≥50kg and that of women ≥45kg. The body mass index (BMI= weight (kg)/height (m ²)) is within the range of 18.0 to 32.0 kg/m ² (including the critical value).
  • The eGFR estimated using the CKD-EPI 2021 formula meets the renal function classification criteria of the corresponding group; That is, mild renal insufficiency: 60≤eGFR\< 90 mL/min, moderate renal insufficiency: 30≤eGFR\<" 60 mL/min, severe renal insufficiency: eGFR\<" 30 mL/min without dialysis, normal renal function: 90≤eGFR\<" 130 mL/min;
  • The two eGFR results during the screening period and the baseline period (CKD-EPI 2021 formula, with an interval of ≥72 hours between the two) must be within the same renal function classification.
  • Participants with normal renal function and no previous serious primary diseases of vital organs, including but not limited to circulatory system, coagulation system, endocrine system, skin system, nervous system, digestive system, respiratory system, hematology, immunology, psychiatry and metabolic abnormalities;
  • At the time of screening, the normal or abnormal results of vital signs, physical examination, laboratory tests (blood routine, blood biochemistry, urine routine, coagulation function), frontal chest X-ray or chest CT and abdominal color Doppler ultrasound of the participants in the normal renal function group had no clinical significance.
  • For the renal insufficiency group, the researcher evaluated and diagnosed it as chronic kidney disease (with any indicators of renal damage or eGFR less than 60 mL/min for more than 3 months) and/or having stable renal function;
  • For the renal insufficiency group, no new prescription drugs, over-the-counter drugs, Chinese herbal medicines or health products were used within two weeks prior to screening, in addition to the treatment plans already used for the primary disease. Those who had stable medication for renal insufficiency for at least 4 weeks before screening (as determined by the researcher, excluding drugs contraindicated in the treatment plan) and did not change the treatment plan during the study period;
  • The demographic mean of participants in the normal renal function group at the time of screening must meet the following matching criteria: a) BMI matching was conducted with the renal insufficiency group, with the mean within ±20% (including the critical value); b) Age matching was carried out with the renal insufficiency group, with the mean within ±10 years (including the critical value); c) Gender matching was conducted with the renal insufficiency group, with ±1 participant/gender.
  • Participants (including their partners) had no plans for having children, no plans for sperm or egg donation during the trial period and within 3 months after administration, and agreed to take effective contraceptive measures (for details, see Appendix 2).