chronic kidney disease,hyperuricemia
Conditions
Interventions
Placebo:Placebo
Dotinurad:Dotinurad
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. At the time of signing the informed consent form, subjects are aged 18-80 years, with no gender restriction. 2. At screening (Visit 1), diagnosed with chronic kidney disease and eGFR >= 30 mL/min/1.73 m^2 (2021 CKD-EPI creatinine formula). 3. At least one SUA > 420 µmol/L within the 3 months prior to screening. 4. SUA > 420 µmol/L at screening (Visit 1). 5. At screening (Visit 1), 24-hour urinary UACR > 100 mg/g (11.3 mg/mmol) and <= 3500 mg/g (395.9 mg/mmol). 6. Has been on stable doses of renin-angiotensin system inhibitors (RASi) therapy with stable doses maintained for at least 4 weeks. 7. Contraceptive methods used by female subjects should comply with local regulations regarding contraception in clinical research participants. 8. Prior to entering the study or undergoing any study procedures, provide subjects with a written informed consent form indicating that they understand the study purpose and required procedures and are willing to participate in the study.
Exclusion criteria
Exclusion criteria: 1. With a history of gout attacks and/or clinical manifestations; 2. Have clinical manifestations of urinary tract calculi; 3. History of secondary hyperuricemia: (1) Lesch-Nyhan syndrome; (2) Overactivity of phosphoribosyl pyrophosphate (PRPP) synthetase; (3) Congenital myogenic hyperuricemia; (4) Hematological malignancies (acute leukemia, malignant lymphoma, myeloproliferative neoplasms, myelodysplastic syndrome, etc.); (5) Solid tumors (breast cancer, seminoma, sarcoma, nephroblastoma, small cell lung cancer, etc.); (6) Non-neoplastic diseases (common psoriasis, secondary polycythemia, hemolytic anemia); (7) Rhabdomyolysis; (8) Hypothyroidism; (9) Polycystic kidney disease; (10) Lead poisoning / lead nephropathy; (11) Down syndrome; (12) Familial juvenile gouty nephropathy; (13) Hyperlactic acidemia; (14) Glycogen storage disease type I; 4. Unstable renal function within recent 90 days prior to screening (defined as a decline in estimated glomerular filtration rate [eGFR] > 20%). 5.Uncontrolled hypertension at Screening (Visit 1), defined as a mean systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg based on three consecutive measurements. 6.Hypotension is defined as a mean SBP 3×ULN). 12.Known positive human immunodeficiency virus (HIV) status. 13.Uncontrolled type 2 diabetes mellitus (T2DM) (HbA1c > 8.5% at Screening [Visit 1]). 14.History of solid organ or bone marrow transplantation, or planned solid organ/bone marrow transplantation (including renal transplantation) within 24 weeks after randomization (Visit 2). 15.Planned surgery within 24 weeks after randomization (Visit 2). 16.Any clinically significant disease or condition that, in the investigator’s judgment, may expose the subject to risks from study participation or interfere with the interpretation of study results. 17.History of malignancy within the past 5 years, excluding successfully treated basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ. 18.Receipt of systemic glucocorticoids or immunosuppressant therapy within 6 months prior to screening, ongoing use, or planned use within 24 weeks after randomization (Visit 2). This includes oral or injectable administration for more than one week, or prednisone at a daily dose of =15 mg (or equivalent dose). 19.Receipt of biologic therapy within 6 months prior to screening, ongoing use, or planned use within 24 weeks after randomization (Visit 2). This includes biolo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects whose serum uric acid (SUA) level was = 360 µmol/L at the 24th week;change in the 24-hour urine albumin/creatinine ratio (UACR) at the 24th week compared to the baseline; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in 24-hour urinary uric acid excretion rate (UEUA) at each time point.;Change from baseline in 24-hour urinary total protein/creatinine ratio (UPCR) at each time point.;Incidence of composite renal events;Percentage reduction from baseline in SUA level at each time point.;Change from baseline in fractional excretion of uric acid (FEUA) at each time point;Proportion of subjects with SUA level = 360 µmol/L at Week 4 and Week 12;Proportion of patients with at least one gout flare.;Change from baseline in 24-hour urinary UACR at Week 4 and Week 12.;Change from baseline in random urinary UACR at each time point;Adverse event;Change from baseline in serum creatinine (Scr) at each time point.;Change from baseline in serum indoxyl sulfate at Week 24.;Change from baseline in systolic blood pressure and diastolic blood pressure at Week 24.;Change from baseline in estimated glomerular filtration rate (eGFR) and its slope at each time point.;Change from baseline in random urinary UPCR at each time point.; | — |
Countries
China
Contacts
Public ContactDing Xiaoqiang
Zhongshan Hospital, Fudan University
Outcome results
None listed