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

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

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

Study Overview

• Status: Completed
• Conditions: Hyperuricemia
• Intervention / Treatment: Drug: Placebo; Drug: SHR4640; Drug: benzbromarone

• Study Type: Interventional
• Enrollment (Actual): 198
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Jiangsu HengRui Medicine Co., Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Chunde Bao, Shanghai Jiaotong University, School of Medicine, Renji Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2017
• Primary Completion (Actual): July 20, 2018
• Study Completion (Actual): July 20, 2018

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 12, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): August 7, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: SHR4640, Phase II, monotherapy, dose-finding
• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia; Antirheumatic Agents; Gout Suppressants; Renal Agents; Uricosuric Agents; Benzbromarone
• Other Study ID Numbers: SHR4640-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No