ruzinurad (SHR 4640) / Jiangsu Hengrui Pharma - LARVOL DELTA

Ruzinurad for hyperuricemia associated with primary gout: a multicenter, randomized, double-blind, active-controlled, phase 3 study (EULAR 2025) - P3 | "The URAT1 inhibitor ruzinurad demonstrated superior sUA lowering effect over allopurinol, along with a well-tolerated safety profile, in patients with hyperuricemia associated with primary gout."

Clinical • P3 data • Gout • Infectious Disease • Inflammatory Arthritis • Respiratory Diseases • Rheumatology

A Multicentre, Randomized, Double-blind, Allopurinol Controlled Study to Evaluate the Efficacy and Safety of SHR4640 in Subjects With Gout (clinicaltrials.gov) - P3 | N=779 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Gout • Inflammatory Arthritis • Rheumatology

Evaluating the Drug-Drug Interactions of SHR4640 on Repaglinide and midazolam in healthy subjects. (PubMed, Expert Opin Drug Metab Toxicol) - P1 | "SHR4640 exerts a weak inhibitory effect on the AUC of CYP enzyme probe substrates and has minimal potential for drug-drug interactions and presents a favorable safety profile. www.clinicaltrials.gov identifier is NCT06196580 (Name: PK Effects of SHR4640 on Repaglinide and Midazolam, and the Impact of SHR4640 on QT Interval)."

Clinical • Journal • CYP3A4

Effect of Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of SHR4640, a Selective Human Urate Transporter 1 Inhibitor. (PubMed, J Clin Pharmacol) - "Mild and moderate hepatic impairment did not have a clinically relevant impact on PK, PD, and safety of SHR4640. SHR4640 can be used in patients with mild to moderate hepatic impairment without the need for dose adjustment."

Journal • PK/PD data • Hepatology

Pharmacokinetic/Pharmacokinetic and Safety Studies of SHR4640 in Subjects With Moderate Renal Insufficiency and Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Recruiting ➔ Completed | Trial completion date: Nov 2023 ➔ Jul 2024 | Trial primary completion date: Nov 2023 ➔ Jul 2024

Trial completion • Trial completion date • Trial primary completion date • Nephrology • Renal Disease

A 12-WEEK, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 STUDY OF RUZINURAD (SHR4640) IN COMBINATION WITH FEBUXOSTAT FOR PRIMARY GOUT AND HYPERURICEMIA WITH AN INADEQUATE RESPONSE TO FEBUXOSTAT ALONE (EULAR 2024) - P2 | "Addition of the URAT1 inhibitor ruzinurad (both 10 and 5 mg) to febuxostat demonstrated superior sUA lowering effect versus placebo plus febuxostat and was generally well-tolerated in patients with primary gout and hyperuricemia uncontrolled on febuxostat alone."

Clinical • Combination therapy • P2 data • Gout • Inflammatory Arthritis • Rheumatology

PK Effects of SHR4640 on Repaglinide and Midazolam, and the Impact of SHR4640 on QT Interval (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Recruiting ➔ Completed

Trial completion • Gout • Inflammatory Arthritis • Rheumatology

PK Effects of SHR4640 on Repaglinide and Midazolam, and the Impact of SHR4640 on QT Interval (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

Bioequivalence Study of 2 Sizes of SHR4640 Tablets Orally in Healthy Subjects (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion

PK Effects of SHR4640 on Repaglinide and Midazolam, and the Impact of SHR4640 on QT Interval (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P1 trial • Gout • Inflammatory Arthritis • Rheumatology

Bioequivalence Study of 2 Sizes of SHR4640 Tablets Orally in Healthy Subjects (clinicaltrials.gov) - P1 | N=34 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

Bioequivalence Study of 2 Sizes of SHR4640 Tablets Orally in Healthy Subjects (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P1 trial

Systematic review and model-based analysis to identify whether renal safety risks of URAT1 inhibitors are fully determined by uric acid-lowering efficacies. (PubMed, Semin Arthritis Rheum) - "Uric acid-lowering efficacy is not an independent factor for the renal safety risk of different URAT1 inhibitors, and structural differences could be responsible for the difference. The adverse renal effects of URAT1 inhibitors are dose-dependent, and the combination with high doses of XOIs can significantly reduce the renal safety risk by reducing uric acid excretion by the kidneys."

Journal • Review

Pharmacokinetic/Pharmacokinetic and Safety Studies of SHR4640 in Subjects With Moderate Renal Insufficiency and Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Nephrology • Renal Disease

A Multicentre, Randomized, Double-blind, Allopurinol Controlled Study to Evaluate the Efficacy and Safety of SHR4640 in Subjects With Gout (clinicaltrials.gov) - P3 | N=780 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gout • Inflammatory Arthritis • Rheumatology

Pharmacokinetic/Pharmacokinetic and Safety Studies of SHR4640 in Subjects With Moderate Renal Insufficiency and Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P1 trial • Nephrology • Renal Disease

Effect of Food on the Pharmacokinetics and Pharmacodynamics of a Single Oral Dose of SHR4640, a Selective Urate Transporter 1 Inhibitor, in Healthy Chinese Male Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "A single 10-mg dose of SHR4640 was safe and well tolerated in this trial. The main pharmacokinetic parameters and serum uric acid lowering of SHR4640 were not affected by food effect; thus, SHR4640 can be recommended to be administered with or without food."

Journal • PK/PD data • Gout • Inflammatory Arthritis • Rheumatology

A drug-drug interaction study of a novel, selective urate reabsorption inhibitor SHR4640 and xanthine oxidase inhibitor febuxostat in patients with primary hyperuricemia. (PubMed, J Clin Pharmacol) - "Co-administration of SHR4640 with febuxostat was not associated with any clinically relevant pharmacokinetic drug interactions. SHR4640 combined with febuxostat had a synergistic effect on reducing uric acid in pharmacodynamics, with AUC decreased from 7440 to 3170 h*umol/L compared with febuxostat alone and 5730 to 2960 h*umol/L compared with SHR4640 alone."

Journal • Gout • Inflammatory Arthritis • Rheumatology

A Multicentre, Randomized, Double-blind, Allopurinol Controlled Study to Evaluate the Efficacy and Safety of SHR4640 in Subjects With Gout (clinicaltrials.gov) - P3 | N=708 | Recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | N=288 ➔ 708 | Trial completion date: Aug 2022 ➔ Jul 2024 | Trial primary completion date: Dec 2021 ➔ Jul 2024

Enrollment change • Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

Clinical Study of SHR4640 Tablets Combined With Febuxostat Tablets in the Treatment of Primary Gout and Hyperuricemia (clinicaltrials.gov) - P2 | N=129 | Not yet recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd.

New P2 trial • Gout • Inflammatory Arthritis • Rheumatology

Pharmacokinetics, Pharmacodynamics and Safety of SHR4640 in Patients With Hepatic Impairment (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Hepatology

Pharmacokinetics, Pharmacodynamics and Safety of SHR4640 in Patients With Hepatic Impairment (clinicaltrials.gov) - P1 | N=24 | Enrolling by invitation | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Unknown status ➔ Enrolling by invitation | Trial completion date: Feb 2021 ➔ Dec 2022 | Trial primary completion date: Feb 2021 ➔ Dec 2022

Enrollment open • Trial completion date • Trial primary completion date • Hepatology

Drug Interaction Between SHR4640 Tablets and Furosemide Tablets in Healthy Volunteers (Single Center, Single Arm, Open, Self-control) (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Recruiting ➔ Completed

Trial completion

A Study of Evaluating the Efficacy and Safety of SHR4640 in Subjects With Gout (clinicaltrials.gov) - P3 | N=594 | Completed | Sponsor: Jiangsu HengRui Medicine Co., Ltd. | Recruiting ➔ Completed | N=880 ➔ 594 | Trial primary completion date: Mar 2021 ➔ Jul 2021

Enrollment change • Monotherapy • Trial completion • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

Safety and efficacy of SHR4640 combined with febuxostat for primary hyperuricemia: a multicenter, randomized, double-blind, phase II study. (PubMed, Ther Adv Musculoskelet Dis) - "SHR4640 plus febuxostat exhibited a tolerable safety profile and substantial sUA lowering activity in patients with primary hyperuricemia. www.chinadrugtrials.org.cn; CTR 20192429."

Clinical • Journal • P2 data • Gout • Inflammatory Arthritis • Rheumatology