ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 1229

AR882, a Potent and Selective Uric Acid Lowering Agent Acting Through Inhibition of Uric Acid Reuptake, Shows Excellent Pharmacokinetics and Pharmacodynamics in a Phase 1 Clinical Trial

zancong shen 1, Elizabeth Polvent 2, Vijay Hingorani 3, Shunqi Yan 4, Rongzi Yan 4 and Litain Yeh4, 1Arthrosi Therapeutics, San Diego, CA, 2Arthrosi Therapeutics, Laguna Hills, CA, 3Arthrosi Therapeutics, San Diego, 4Arthrosi Therapeutics, Laguna Hills

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: hyperuricemia, Single-ascending dose, URAT1, urate lowering and urinary excretion

  • Tweet
  • Email
  • Print
Session Information

Date: Monday, November 11, 2019

Session Title: Metabolic & Crystal Arthropathies Poster II: Clinical Trials & Basic Science

Session Type: Poster Session (Monday)

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

Background/Purpose: AR882 is a potent and selective uric acid transporter 1 (URAT1) inhibitor under development for the treatment of hyperuricemia or gout. A Phase 1 single ascending dose clinical study in healthy adult male subjects was conducted to evaluate pharmacokinetics and dose-dependent serum uric acid (sUA) lowering effect.

Methods: Analysis of sUA reduction was conducted in a randomized, double-blind, placebo-controlled single dose study with 31 healthy male volunteers. Eight subjects per group (6 active and 2 placebo) were planned to be dosed AR882 under fasted conditions at 15, 50, or 100 mg with an immediate release formulation, or at 50 mg following a high-fat, high- calorie meal. Correlation of increased uric acid excretion in urine with sUA lowering was assessed to further evaluate the effect of URAT1 inhibition in the tubule. Laboratory safety tests, vital signs, and electrocardiograms were collected throughout the study

Results: Following administration of AR882, exposure of AR882 exhibited dose proportional increase and was significantly lower than the no-observed-adverse-effect level (NOAEL) in rats and monkeys.  The rate of absorption was moderate (Tmax 3-5 hours) with a half-life of AR882 of approximately 10-13 hours. When administrated with a high-fat, high-calorie meal, AR882 absorption was slower (Tmax 8 hours), with Cmax lowered by approximately 33% but AUC was similar to that in the fasting conditions. The mean changes in sUA at the 24 hours postdose from baseline were 2.0% in the pooled placebo group, -5.8%, -42.4% and -58.4% in the 15 mg, 50 mg (P< 0.001 vs placebo) and 100 mg (P< 0.001 vs placebo) fasted groups, respectively.  Time to reach highest sUA reduction range between 12 – 36 hr post-dose with median TEmax at 24 hr post-dose.  sUA returned to baseline after 4 to 5 days post-dose following 50 mg and 100 mg dosing. Food did not alter sUA lowering effect of AR882.  sUA lowering effect was similar among subjects irrespective of differing sUA baseline values which ranged between 3 to 9 mg/dL.  Urinary excretion of AR882 and uric acid were evaluated on Day 1 at 6 to 12 hours intervals. Significantly higher amounts of uric acid were eliminated through urine on Day 1 at all collection intervals, indicating sustained inhibition of URAT1 over 24 hours following dosing.  AR882 was well tolerated at all doses tested. All adverse events (AEs) were mild in severity and no serious adverse events (SAEs) were reported. There were no clinically significant laboratory or ECG abnormalities noted.

Conclusion: AR882 exhibited outstanding ability to reduce sUA level at ≥ 50 mg ( > 40% reduction following a single dose). It is anticipated the sUA lowering will accumulate following multiple doses.


Disclosure: z. shen, arthrosi, 3, arthrosi therapeutics, 3; E. Polvent, Arthrosi Therapeutics, Inc., 3, 4; V. Hingorani, arthrosi therapeutics, 5, arthrosi therapeutics, 5; S. Yan, Arthrosi Therapeutics, Inc., 1, 3, 4, 6; R. Yan, None; L. Yeh, None.

To cite this abstract in AMA style:

shen z, Polvent E, Hingorani V, Yan S, Yan R, Yeh L. AR882, a Potent and Selective Uric Acid Lowering Agent Acting Through Inhibition of Uric Acid Reuptake, Shows Excellent Pharmacokinetics and Pharmacodynamics in a Phase 1 Clinical Trial [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/ar882-a-potent-and-selective-uric-acid-lowering-agent-acting-through-inhibition-of-uric-acid-reuptake-shows-excellent-pharmacokinetics-and-pharmacodynamics-in-a-phase-1-clinical-trial/. Accessed July 3, 2022.
  • Tweet
  • Email
  • Print

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/ar882-a-potent-and-selective-uric-acid-lowering-agent-acting-through-inhibition-of-uric-acid-reuptake-shows-excellent-pharmacokinetics-and-pharmacodynamics-in-a-phase-1-clinical-trial/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2022 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies