Dose-finding and Safety Study of SHR4640 in Subjects With Hyperuricemia

Study Overview
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Brief Summary
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The objective of the study is to assess efficacy and safety of SHR4640 in subjects with hyperuricemia.

Official Title
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Dose-finding and Safety Study of SHR4640 in Subjects With Hyperuricemia (Asymptomatic and Gout)

Conditions
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Hyperuricemia

Intervention / Treatment
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* Drug: Placebo
* Drug: SHR4640
* Drug: benzbromarone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years, male or female; 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: Subject who is pregnant or breastfeeding; Alanine aminotransferase or Aspartate aminotransferase or total bilirubin>1.5 upper normal limit; Estimated glomerular filtration rate (MDRD formula) ˂60ml/min; HbA1c˃8%; Subject with known hypersensitivity or allergy to SHR4640 or any component of SHR4640; Subject with a history of malignancy; Subject with a history of urolithiasis, or positive findings on ultrasound examination at screen 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; Subject has acute gout flares within 2 weeks before randomization; 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; 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; Subject who is taking any diuretic within 2 weeks before randomization and can not stop during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo for 5 weeks | Drug: Placebo<br>* Placebo once daily for 5 weeks<br>|
| Experimental: 2.5mg SHR4640<br>SHR4640 for 5 weeks | Drug: SHR4640<br>* 1mg SHR4640 once daily for a week, 2.5mg, 5mg or 10mg SHR4640 once daily for 4 weeks<br>|
| Experimental: 5mg SHR4640<br>SHR4640 for 5 weeks | Drug: SHR4640<br>* 1mg SHR4640 once daily for a week, 2.5mg, 5mg or 10mg SHR4640 once daily for 4 weeks<br>|
| Experimental: 10mg SHR4640<br>SHR4640 for 5 weeks | Drug: SHR4640<br>* 1mg SHR4640 once daily for a week, 2.5mg, 5mg or 10mg SHR4640 once daily for 4 weeks<br>|
| Active Comparator: 50mg benzbromarone<br>Benzbromarone for 5 weeks | Drug: benzbromarone<br>* 25mg benzbromarone once daily for a week, 50mg benzbromarone once daily for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with a serum uric level≤360μmol/l. |  | Week 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actual change from baseline in serum uric level. |  | Week 5 | 
| Percentage change from baseline in serum uric level . |  | Week 5 | 
| Rate of gout flares requiring treatment. |  | Up to week 5 | 
| Incidence of gout flares requiring treatment. |  | Up to week 5 | 
| Proportion of subjects with a serum uric level≤360μmol/l |  | At week1, 2, 3 and 4 | 
| Proportion of subjects with a serum uric level consistent ≤360μmol/l |  | At week 3, 4 and 5 | 
| Actual change from baseline in serum uric level |  | At week 1, 2, 3 and 4 | 
| Percentage change from baseline in serum uric level |  | At week 1, 2, 3 and 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHR4640, Phase II, monotherapy, dose-finding