Pharmos, a biopharmaceutical company based in Iselin, N.J., has successfully completed a proof-of-concept clinical trial using its compound levotofisopam (S-tofisopam) to treat patients with hyperuricemia and gout.
The open label phase IIa study, conducted at the clinical research unit of Duke University, was designed to assess the safety and efficacy of levotofisopam as a uric acid-lowering agent in patients with gout. The trial enrolled 13 patients with screening serum urate between 8 and 12mg/dL. Subjects received a single dose of levotofisopam 50mg on days 1 and 7 and 50mg three times daily on days 2 through 6, and were confined in the Duke facility.
Levotofisopam was well tolerated. The mean reduction in serum urate was over 45%. All 13 patients were responders and demonstrated a serum urate level of less than 6mg/dL on day 7. Seven subjects achieved a serum urate level less than 4mg/dL on day 7. Additionally, there was an increase in the fractional excretion of urate, confirming the compound's mechanism of action as a uricosuric agent that enhances urate excretion by the kidneys.
This trial follows two prior phase I clinical studies conducted by Vela Pharmaceuticals (merged with Pharmos in October 2006). In these studies, conducted in healthy volunteers in the U.K. and The Netherlands, levotofisopam treatment was generally well tolerated and was associated with a large and rapid reduction in serum uric acid values.
“Given that the compound is safe, and has been exposed to 90 subjects in total, levotofisopam should be an attractive compound for a pharmaceutical company to partner or license,” said S. Colin Neill, president, Pharmos. “Achieving a partnership is now our primary objective."
Levotofisopam is the S-enantiomer of the racemic mixture RS-tofisopam, a well tolerated agent used for the treatment of a variety of disorders associated with stress or autonomic instability. Racemic tofisopam is not marketed in the U.S. but has been approved since 1974 and marketed in more than 20 other countries around the world. Dextofisopam, the R-enantiomer, is being developed for the treatment of irritable bowel syndrome (IBS) and has completed testing through phase IIb in the U.S.