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

NCT03185793 | Completed Phase 2 DMC

• 1 other identifier: SHR4640-201
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hyperuricemia

Keywords

SHR4640, Phase II, monotherapy, dose-finding

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with a serum uric level≤360μmol/l.

  Week 5

Secondary Outcomes (8)

• 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

Study Arms (5)

Placebo

PLACEBO COMPARATOR

placebo for 5 weeks

Drug: Placebo

2.5mg SHR4640

EXPERIMENTAL

SHR4640 for 5 weeks

Drug: SHR4640

5mg SHR4640

EXPERIMENTAL

SHR4640 for 5 weeks

Drug: SHR4640

10mg SHR4640

EXPERIMENTAL

SHR4640 for 5 weeks

Drug: SHR4640

50mg benzbromarone

ACTIVE COMPARATOR

Benzbromarone for 5 weeks

Drug: benzbromarone

Interventions

Placebo DRUG

Placebo once daily for 5 weeks

Placebo

SHR4640 DRUG

1mg SHR4640 once daily for a week, 2.5mg, 5mg or 10mg SHR4640 once daily for 4 weeks

10mg SHR4640; 2.5mg SHR4640; 5mg SHR4640

benzbromarone DRUG

25mg benzbromarone once daily for a week, 50mg benzbromarone once daily for 4 weeks

50mg benzbromarone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years, male or female;
• Subject meets one of the following conditions:
• \) 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Jiangsu Hengrui Medicine Co., Ltd.

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (1)

• 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.

  PMID: 33693494 DERIVED

MeSH Terms

Conditions

Hyperuricemia

Interventions

ruzinurad; Benzbromarone

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Chunde Bao

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 14, 2017
• Study Start: July 20, 2017
• Primary Completion: July 20, 2018
• Study Completion: July 20, 2018
• Last Updated: August 7, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)