A Series of Double-Blind, Placebo-Controlled, Randomized, Multicenter, Phase 2 Studies to Evaluate the Efficacy, Safety, and Dose-Response Relationship of Orally Administered URC102, a Novel URAT1 Inhibitor, in Korean Patients with Gout

Jae-Bum Jun¹, Howard Lee², Chang-Hee Suh³, Chang Keun Lee⁴, Dong Wook Kim⁵, Jung-Yoon Choe⁶, Sang-Heon Lee⁷, Sang-Hyon Kim⁸, Seung-Jae Hong⁹, So-Young Bang¹⁰, Sung Jae Choi¹¹, Yong-Beom Park¹², Makoto Onohara¹³, Jeongeun Choi¹⁴, Jung Soo Song¹⁵ and Won Park¹⁶, ¹Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South), ²Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea, Republic of (South), ³Ajou University School of Medicine, Suwon, Korea, Republic of (South), ⁴Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic of (South), ⁵Division of Rheumatology, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea, Republic of (South), ⁶Division of Rheumatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea, Republic of (South), ⁷Division of Rheumatology, Department of Internal Medicine,, Konkuk University School of Medicine, Seoul, Korea, Republic of (South), ⁸Division of Rheumatology, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea, Daegu, Korea, Republic of (South), ⁹Department of Rheumatology, Kyung Hee University Medical Center, Seoul, Korea, Republic of (South), ¹⁰Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South), ¹¹Internal Medicine, Korea University Medical Center, Seoul, Korea, Republic of (South), ¹²Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), ¹³Science and Strategy, Translational Clinical Research, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan, ¹⁴JW Pharmaceutical Corporation, Seoul, Korea, Republic of (South), ¹⁵Rheumatology, Chung-Ang University College of Medicine, Seoul, Korea, Republic of (South), ¹⁶Medicine/Rheumatology, Inha University Hospital, Incheon, Korea, Republic of (South)

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: clinical trials, gout, hyperuricemia and uric acid

Session Information

Date: Tuesday, November 7, 2017

Title: Metabolic and Crystal Arthropathies Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

URC102 is a novel URAT1 inhibitor under clinical development for the treatment of hyperuricemia with gout. A series of double-blind, placebo-controlled, randomized, multicenter, phase 2 studies investigated the efficacy, safety, and dose-response relationship of URC102 in patients with gout (NCT02290210 and NCT02557126).

Methods:

Korean male patients aged ≥20 and <70 years with gout and serum uric acid (sUA) levels ≥7.0 mg/dL and ≤10.0 mg/dL at screening were randomized to orally (QD) receive placebo or URC102 at 0.25 mg, 0.5 mg, 1 mg, and 2 mg (first study with low-dose URC102) and placebo or URC102 at 3 mg, 5mg, 7 mg, and 10 mg (second study with high-dose URC102) for 14 days. Efficacy was evaluated by analyzing the trend of sUA reduction, defined as percentage changes of sUA for 2 weeks with reference to baseline, after administration of URC102. Safety was assessed with adverse events (AEs), physical examinations, and laboratory findings throughout the studies.

Results:

Sixty-four (first study) and 76 (second study) patients with gout were randomized. The mean percentage changes (± standard deviation) of sUA on Day 15 was -3.96 (±15.77)%, -3.28 (±10.39)%, -10.63 (±10.09)%, -13.15 (±20.30)%, and -29.52 (±8.45)% in the placebo, URC102 0.25 mg, 0.5 mg, 1 mg, and 2 mg groups, respectively (first study), and -1.20 (±7.75)%, -28.31 (±15.17)%, -44.02 (±20.11)%, -49.05 (±10.76)%, and -54.31 (±12.38)% in the placebo, URC102 3 mg, 5 mg, 7 mg, and 10 mg groups, respectively (second study). AEs that occurred with a frequency of 10% or more, regardless of causality, were arthralgia and pain in extremity (first study) and gout and arthralgia (second study). Most of the AEs were mild in severity, and there were no significant differences in the frequency of AEs between the placebo and URC102 treatment groups. Two serious AEs, animal bite and traffic accident, were reported, but the causality to the study drug was unrelated in both events.

Conclusion:

URC102 decreased sUA levels in a dose-dependent manner in Korean patients with gout. All doses of orally administered URC102 for 14 days were well tolerated. Further long-term clinical studies in larger populations are warranted to evaluate the effectiveness of URC102, which could be a new effective treatment option as a urate-lowering therapy.

Disclosure: J. B. Jun, None; H. Lee, None; C. H. Suh, None; C. K. Lee, None; D. W. Kim, None; J. Y. Choe, None; S. H. Lee, None; S. H. Kim, None; S. J. Hong, None; S. Y. Bang, None; S. J. Choi, None; Y. B. Park, None; M. Onohara, Chugai Pharmaceutical Co., Ltd., 3; J. Choi, JW Pharmaceutical Corporation, 3; J. S. Song, None; W. Park, None.

To cite this abstract in AMA style:

Jun JB, Lee H, Suh CH, Lee CK, Kim DW, Choe JY, Lee SH, Kim SH, Hong SJ, Bang SY, Choi SJ, Park YB, Onohara M, Choi J, Song JS, Park W. A Series of Double-Blind, Placebo-Controlled, Randomized, Multicenter, Phase 2 Studies to Evaluate the Efficacy, Safety, and Dose-Response Relationship of Orally Administered URC102, a Novel URAT1 Inhibitor, in Korean Patients with Gout [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/a-series-of-double-blind-placebo-controlled-randomized-multicenter-phase-2-studies-to-evaluate-the-efficacy-safety-and-dose-response-relationship-of-orally-administered-urc102-a-novel-urat1-inh/. Accessed .

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