Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Brief summary
The study is being conducted to compare the pharmacokinetics, safety, and pharmacodynamics of HSK39297 in subjects with mild to moderate hepatic impairment and normal hepatic function
Interventions
DRUGHSK39297 tablets
oral
Sponsors
Haisco Pharmaceutical Group Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Ability to understand the study procedures and methods, participate voluntarily and be able to complete the study according to the protocol requirements, and sign the informed consent form (ICF) in writing; 2. Aged 18-70 years old on the date of signing the ICF (including the threshold), both male and female; 3. At the time of screening, male subjects weighing no less than 50 kg and female subjects weighing no less than 45 kg; body mass index (BMI): 18\ 32 kg/m2 (including the threshold); 4. Normal or abnormal physical examination, 12-ECG, vital signs, chest frontal and lateral radiographs/CT, abdominal ultrasound, and laboratory tests (blood routine, blood biochemistry, urine routine, coagulation function, etc.) in the screening and baseline periods were not clinically significant. 5. The demographic means of subjects in the normal liver function group (Group C) at screening must meet the following matching criteria: 1. BMI matched to the hepatic impairment group (Group A + Group B) with a mean value ± 15%; 2. Age-matched to the hepatic impairment group (Group A + Group B), mean ± 10 years; 3. Sex-matched to liver impairment group (Group A + Group B), mean value ± 1 case; 6. Glomerular filtration rate (eGFR) ≥75 mL/min/1.73m2 calculated using the Chronic Kidney Disease Epidemiology Collaborative Study Group (CKD-EPI) formula; 7. Subjects with childbearing potential must agree to have no plans for childbearing and voluntarily use highly effective contraception with their partner from the time of signing the ICF until 1 month after administration of the test drug, and to avoid sperm/egg donation. Female subjects of childbearing potential must have a negative serum pregnancy test at both screening and baseline and not be breastfeeding. For subjects with hepatic impairment, the following inclusion criteria must also be met: 8. Not on medication within 4 weeks prior to screening, or have at least 4 weeks of stable medication for hepatic impairment and/or other co-morbidities requiring long-term treatment; 9. Child-Pugh classification of Class A or B (without the use of albumin within 14 days), which is chronic liver injury caused by previous primary liver diseases, including but not limited to non-alcoholic steatohepatitis, viral hepatitis (hepatitis B, hepatitis C), etc.
Exclusion criteria
1. Smoked an average of more than 5 cigarettes per day in the past 3 months or those who cannot comply with the prohibition of smoking during the trial; 2. Known or suspected (as judged by the researcher) immunodeficiency diseases or hereditary complement deficiencies; 3. Allergic to two or more allergens, or in the judgment of the investigator, may be allergic to the study drug or its components; 4. Screen those who have a history of heavy drinking in the past 3 months (with an average daily alcohol consumption of \> 2 units of alcohol (1 unit = 285 mL of beer, or 30 mL of spirits, or 100 mL of wine)) or those with a positive breath alcohol test; 5. Disease or medical condition that, in the judgment of the investigator, may interfere with the absorption, distribution, metabolism, and excretion of the drug or that may reduce compliance; 6. History of capsular bacterial infection in the past; including but not limited to Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, etc; 7. Severe trauma or undergone surgery within 2 weeks prior to screening, or plan to undergo surgery during the trial period; 8. Participated in a clinical trial of any other drug or medical device within 3 months prior to screening or plan to do so during the study period, or still within 5 half-lives of the drug prior to screening (whichever is longer); 9. A previous diagnosis of malignant tumors (excluding radically resected basal cell carcinoma of the skin, papillary thyroid carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix); 10. History of drug or substance abuse; or a positive urine drug test at screening; 11. Donated or lost ≥ 400 mL of blood within 30 days, or received a blood transfusion prior to screening; 12. QTcF (males) \> 480 ms at screening, or other 12-ECG abnormalities judged by the investigator to be clinically significant or unsuitable for participation; 13. Difficulty in swallowing, collecting blood intravenously, or physically unable to tolerate blood collection, or not expected to complete the entire trial follow-up; 14. Vaccined within 2 weeks prior to dosing or plan to receive the vaccine during the study; 15. Positive result in the screening of any of the following indicators: hepatitis B surface antigen, hepatitis C antibody, HIV antibody, or syphilis antibody (hepatitis B surface antigen and hepatitis C antibody can be positive in subjects in the liver insufficiency group). 16. Any physical or psychological disease or condition that, in the judgment of the investigator, is likely to increase the risk of the trial, interfere with compliance with the protocol and ability to complete the trial. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Post-dose at day 1 to day 10. | The maximum plasma concentration. |
| AUC0-t | Post-dose at day 1 to day 10 | Area under the concentration curve from time 0 to the last quantifiable concentration |
| AUC0-inf | Post-dose at day 1 to day 10 | Area under the concentration curve from time 0 to extrapolated infinite time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vz/F | Post-dose at day 1 to day 10 | Apparent volume of distribution |
| Tmax | Post-dose at day 1 to day 10 | Time to maximum plasma concentration |
| Incidence and severity of adverse events | Screening period up to day 10 | — |
| t1/2 | Post-dose at day 1 to day 10 | Terminal half-life |
| CL/F | Post-dose at day 1 to day 10 | Apparent clearance |
Countries
China
Contacts
Primary ContactChen Meixia
Outcome results
None listed