Complement Mediated Primary or Secondary Glomerular Diseases
Conditions
Brief summary
The study is being conducted to compare the pharmacokinetics, safety, and pharmacodynamics of HRS-5965 in subjects with mild to moderate hepatic impairment and normal hepatic function.
Interventions
Oral 50 mg.
Sponsors
Chengdu Suncadia Medicine 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. 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: 5. 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; 6. Child-Pugh classification of Class A or B. For subjects with normal hepatic function, the following inclusion criteria must also be met: 7. The demographic means of subjects in the normal liver function group (Group C) at screening must meet the following matching criteria: 1. Weight matched to the hepatic impairment group (Group A + Group B) with a mean value ± 10 kg; 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; 8. 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.
Exclusion criteria
1. Allergic to two or more allergens, or in the judgment of the investigator, may be allergic to the study drug or its components; 2. 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; 3. Prior history of meningococcal infection or a first-degree relative with a history of meningococcal infection; 4. Existing or suspected infection (at the investigator's discretion) within 2 weeks prior to screening, or fever; 5. Severe trauma or undergone surgery within 8 weeks prior to screening, or plan to undergo surgery during the trial period; 6. 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); 7. Smoked an average of more than 5 cigarettes per day in the 4 weeks, or consumed an average of more than 15 g of alcohol in a day in the 4 weeks prior to screening (15 g of alcohol is equivalent to 450 mL of beer, 150 mL of wine, or 50 mL of low-potency liquor), or a positive breath alcohol test at baseline; 8. History of drug or substance abuse; or a positive urine drug test at screening; 9. Donated or lost ≥ 400 mL of blood within 8 weeks, or received a blood transfusion within 12 weeks prior to screening; 10. Malignant tumor, or history of a malignant tumor within 5 years prior to screening (except for primary hepatocellular carcinoma treated with radical surgery without recurrence within 2 years, non-melanoma of the skin for which treatment has been administered without signs of recurrence, and resected cervical intraepithelial neoplasia); 11. Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg at screening; 12. QTcF (males) \> 450 ms and a QTcF (females) \> 470 ms at screening, or other 12-ECG abnormalities judged by the investigator to be clinically significant or unsuitable for participation; 13. Glomerular filtration rate (eGFR) \< 75 mL/min/1.73m2 calculated using the Chronic Kidney Disease Epidemiology Collaborative Study Group (CKD-EPI) formula; 14. Difficulty in swallowing, collecting blood intravenously, or physically unable to tolerate blood collection, or not expected to complete the entire trial follow-up; 15. Vaccinated within 2 weeks prior to dosing or plan to receive the vaccine during the study and within 1 month after dosing; 16. Pre-existing recurrent oral ulcers; 17. 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 9. | The maximum plasma concentration. |
| AUClast | Post-dose at day 1 to day 9. | Area under the concentration curve from time 0 to the last quantifiable concentration. |
| AUCinf | Post-dose at day 1 to day 9. | Area under the concentration curve from time 0 to extrapolated infinite time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | Post-dose at day 1 to day 9. | Time to maximum plasma concentration. |
| t1/2 | Post-dose at day 1 to day 9. | Terminal half-life. |
| CL/F | Post-dose at day 1 to day 9. | Apparent clearance. |
| Vz/F | Post-dose at day 1 to day 9. | Apparent volume of distribution. |
| Incidence and severity of adverse events | Screening period up to day 9. | — |
| Change from baseline of alternative pathway activity | Post-dose at day 1. | — |
Countries
China
Outcome results
None listed