Clinical trial NCT03185793: Dose-finding and Safety Study of SHR4640 in Subjects With Hyperuricemia
Official title: Dose-finding and Safety Study of SHR4640 in Subjects With Hyperuricemia (Asymptomatic and Gout)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperuricemia
Keywords: SHR4640, Phase II, monotherapy, dose-finding
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-06-14
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to assess efficacy and safety of SHR4640 in subjects with hyperuricemia.


Eligibility criteria: Inclusion Criteria:

1. 18-70 years, male or female;
2. Subject meets one of the following conditions:

1) Subject with a history of gout has a serum uric acid ≥480μmol/l at screening; 2) Subject with a history of hyperuricemia has a serum uric acid ≥540μmol/l at screening, and requiring long-term uric acid-lowering therapy per the investigator's judgment; 3) Subject with a history of hyperuricemia has a serum uric acid≥480μmol/l at screening, on stable treatment for hypertensive, hyperlipidemia or diabetes for at least 3 month, and requiring long-term uric acid-lowering therapy per the investigator's judgment; 3. 18kg/m2≤ BMI ≤32kg/m2.

Exclusion Criteria:

1. Subject who is pregnant or breastfeeding;
2. Alanine aminotransferase or Aspartate aminotransferase or total bilirubin\>1.5 upper normal limit;
3. Estimated glomerular filtration rate (MDRD formula) ˂60ml/min;
4. HbA1c˃8%;
5. Subject with known hypersensitivity or allergy to SHR4640 or any component of SHR4640;
6. Subject with a history of malignancy;
7. Subject with a history of urolithiasis, or positive findings on ultrasound examination at screen
8. Subject within the last 3months has: myocardial infarction, angina, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, or transient ischemia attack;
9. Subject has acute gout flares within 2 weeks before randomization;
10. Subject who is taking any other urate-lowering medication (allopurinol, febuxostat, probenecid and benzbromarone) that is indicated within 2 weeks before randomization and can not stop during the study;
11. Subject who is taking more than 100mg once daily or unstable dosage aspirin within 2 weeks before randomization and can not stop during the study;
12. Subject who is taking any diuretic within 2 weeks before randomization and can not stop during the study.

Primary outcomes:
measure: Proportion of subjects with a serum uric level≤360μmol/l.
timeFrame: Week 5
Secondary outcomes:
measure: Actual change from baseline in serum uric level.
timeFrame: Week 5
measure: Percentage change from baseline in serum uric level .
timeFrame: Week 5
measure: Rate of gout flares requiring treatment.
timeFrame: Up to week 5
measure: Incidence of gout flares requiring treatment.
timeFrame: Up to week 5
measure: Proportion of subjects with a serum uric level≤360μmol/l
timeFrame: At week1, 2, 3 and 4
measure: Proportion of subjects with a serum uric level consistent ≤360μmol/l
timeFrame: At week 3, 4 and 5
measure: Actual change from baseline in serum uric level
timeFrame: At week 1, 2, 3 and 4
measure: Percentage change from baseline in serum uric level
timeFrame: At week 1, 2, 3 and 4
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Jiangsu Hengrui Medicine Co., Ltd.
state: Shanghai
Study officials:
affiliation: Shanghai Jiaotong University School of Medicine,Renji Hospital
name: Chunde Bao
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lin Y, Chen X, Ding H, Ye P, Gu J, Wang X, Jiang Z, Li D, Wang Z, Long W, Li Z, Jiang G, Li X, Bi L, Jiang L, Wu J, Guo L, Cai X, Lu X, Chen Q, Chen H, Peng A, Zuo X, Ning R, Zhang Z, Tai Y, Zhang T, Bao C. Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricaemia: a randomized controlled phase II study. Rheumatology (Oxford). 2021 Nov 3;60(11):5089-5097. doi: 10.1093/rheumatology/keab198.