Back to results

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

Primary Purpose

Hyperuricemia

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Placebo

SHR4640

benzbromarone

About this trial

This is an interventional treatment trial for Hyperuricemia focused on measuring SHR4640, Phase II, monotherapy, dose-finding

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Jiangsu Hengrui Medicine Co., Ltd.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Placebo Comparator

Experimental

Active Comparator

Arm Label

Placebo

2.5mg SHR4640

5mg SHR4640

10mg SHR4640

50mg benzbromarone

Arm Description

placebo for 5 weeks

SHR4640 for 5 weeks

Benzbromarone for 5 weeks

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Actual change from baseline in serum uric level.

Percentage change from baseline in serum uric level .

Rate of gout flares requiring treatment.

Incidence of gout flares requiring treatment.

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

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

Actual change from baseline in serum uric level

Percentage change from baseline in serum uric level

Full Information

NCT ID

NCT03185793

First Posted

June 12, 2017

Last Updated

August 5, 2019

Sponsor

Jiangsu HengRui Medicine Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03185793

Brief Title

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

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

July 20, 2017 (Actual)

Primary Completion Date

July 20, 2018 (Actual)

Study Completion Date

July 20, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperuricemia

Keywords

SHR4640, Phase II, monotherapy, dose-finding

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

198 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

placebo for 5 weeks

Arm Title

2.5mg SHR4640

Arm Type

Experimental

Arm Description

SHR4640 for 5 weeks

Arm Title

5mg SHR4640

Arm Type

Experimental

Arm Description

SHR4640 for 5 weeks

Arm Title

10mg SHR4640

Arm Type

Experimental

Arm Description

SHR4640 for 5 weeks

Arm Title

50mg benzbromarone

Arm Type

Active Comparator

Arm Description

Benzbromarone for 5 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo once daily for 5 weeks

Intervention Type

Drug

Intervention Name(s)

SHR4640

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

benzbromarone

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

Week 5

Secondary Outcome Measure Information:

Title

Actual change from baseline in serum uric level.

Time Frame

Week 5

Title

Percentage change from baseline in serum uric level .

Time Frame

Week 5

Title

Rate of gout flares requiring treatment.

Time Frame

Up to week 5

Title

Incidence of gout flares requiring treatment.

Time Frame

Up to week 5

Title

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

Time Frame

At week1, 2, 3 and 4

Title

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

Time Frame

At week 3, 4 and 5

Title

Actual change from baseline in serum uric level

Time Frame

At week 1, 2, 3 and 4

Title

Percentage change from baseline in serum uric level

Time Frame

At week 1, 2, 3 and 4

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chunde Bao

Organizational Affiliation

Shanghai Jiaotong University School of Medicine,Renji Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Jiangsu Hengrui Medicine Co., Ltd.

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200127

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

33693494

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs