ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 818

Levotofisopam Has Uricosuric Activity and Reduces Serum Urate Levels in Patients with Gout

Robert J. Noveck1, Zongyao Wang1, Ann Forsthoefel1, Kristina Sigmon2, Pauliana C. Hall3, John C. Keogh4 and John S. Sundy2, 1Duke Clinical Research Unit, Duke University Medical Center, Durham, NC, 2Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, 3PCH Integrated Regulatory Services, Inc., Laguna Niguel, CA, 4Keogh Medical Writing, Philadelphia, PA

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: clinical trials, Gout and uric acid

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Title: Metabolic and Crystal Arthropathies: Clinical

Session Type: Abstract Submissions (ACR)

Background/Purpose: The investigational new drug levotofisopam is the S-enantiomer of racemic tofisopam, a 2,3-benzodiazepine derivative approved in over 20 countries outside the US for treatment of anxiety and autonomic instability. Two Phase 1 trials of levotofisopam in healthy volunteers demonstrated acceptable safety and unexpected reductions in serum urate (SUA). This finding raised the possibility that levotofisopam may be an effective urate-lowering therapy (ULT) in patients with gout. The objectives of this proof of concept (POC) study were to evaluate the safety and tolerability of levotofisopam and its effect on SUA in patients with hyperuricemia and gout.

Methods: This was an open-label, inpatient study of levotofisopam 50 mg TID administered for 7 days to men and women with hyperuricemia and gout.  Patients were required to have had  1+ gout flare in the previous 6 months,  1+ chronically swollen joint due to gout, or  1+ tophus; and screening SUA ≥8.0 mg/dL and ≤12 mg/dL after stopping ULT for ≥10 days. Key exclusions were estimated GFR <60 mL/min/1.73 m2 and 24-hour urine uric acid excretion >1000 mg. Patients were admitted for 3 days prior to dosing and received levotofisopam 50 mg as a single dose on Day 1, 50 mg TID on Days 2-6, and 50 mg as single dose on Day 7. The primary efficacy variable was % reduction in SUA from baseline to Day 7. Secondary variables included absolute reduction in SUA, proportion of subjects with SUA <6 mg/dL on Day 7, change in fractional excretion of urate, and 24-hour urinary urate on Day 6. Adverse events (AEs) were assessed during the screening, treatment, and follow-up periods.

Results: Twenty patients were to be enrolled, but after 13 subjects were dosed, the primary objective of confirming urate-lowering potential in gout patients was achieved and the study was stopped. Baseline characteristics: mean age 47.7 years (range 39-64); 11M/2F; mean BMI 28.5 kg/m2(range 21-33). Baseline mean SUA was 8.0 mg/dL (range 7.0-9.7). At Day 7, the mean percent reduction in SUA was 48.8% (range 31.1%-64.6%). Mean absolute reduction in SUA was 3.9 mg/dL (range 2.3-5.3), and mean treated SUA was 4.1 mg/dL (range 2.9-5.8). All 13 patients achieved a therapeutic SUA of <6.0 mg/dL. Substantial reduction in SUA was observed, to <5 mg/dL in 10/13 and <4 mg/dL in 7/13 patients. Significant increases in fractional excretion of urate and 24-hour urine urate excretion were observed. There were no serious or severe AEs or premature discontinuations due to AEs. Three patients experienced gout flare. Other AEs were musculoskeletal pain/stiffness (7), headache (6), and dizziness, diarrhea, dyspepsia, toothache, rash, and ECG lead dermatitis (2 each). No clinically meaningful changes were observed in other safety assessments.

Conclusion: Monotherapy with levotofisopam led to clinically meaningful reduction of SUA in patients with hyperuricemia and gout. Treatment was generally well tolerated with 23% of the patients experiencing gout flare. Increased fractional excretion of uric acid suggests that levotofisopam reduces SUA primarily through uricosuric activity. These results support further studies to investigate the potential role of levotofisopam for in the treatment of hyperuricemia in gout.


Disclosure:

R. J. Noveck,

Pharmos,

2,

Ardea,

2,

Metabolex,

2,

Novartis Pharmaceutical Corporation,

2,

Takeda,

2;

Z. Wang,
None;

A. Forsthoefel,
None;

K. Sigmon,
None;

P. C. Hall,

Pharmos,

5;

J. C. Keogh,

Pharmos,

5,

Vela Pharmaceuticals, Inc.,

7;

J. S. Sundy,

Ardea Biosciences,

2,

Ardea Biosciences,

5,

Regeneron,

2,

Regeneron,

5,

Metabolex,

2,

Metabolex,

5,

Pharmos,

2,

Pharmos,

5,

Savient,

5,

Savient,

2,

Celgene,

2,

General Electric,

1,

Academic Partners for Medical Education, LLC,

4,

Medanta Duke Research Institute,

6,

Bristol-Myers Squibb,

2,

Bristol-Myers Squibb,

5.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/levotofisopam-has-uricosuric-activity-and-reduces-serum-urate-levels-in-patients-with-gout/

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 »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology