Treatment of mildly to moderately active ulcerative colitis with a tryptase inhibitor (APC 2059): an open-label pilot study.

Abstract

BACKGROUND:

Mast cells isolated from the colonic mucosa in active ulcerative colitis appear to be partially degranulated, suggesting the release of tryptase.

AIM:

To investigate the safety and activity of APC 2059, a highly specific tryptase inhibitor, in the treatment of ulcerative colitis.

METHODS:

This was an open-label, Phase 2, multicentre pilot study in patients with mildly to moderately active ulcerative colitis, with a disease activity index of 6-9 on a 12-point scale. Fifty-six adults received 20 mg APC 2059 subcutaneously twice daily and 53 completed 28 days of treatment. The primary end-point was response, defined as a final disease activity index of < or = 3. Supplementary analyses were also performed.

RESULTS:

Sixteen (29%) of 56 patients responded. Five (9%) showed complete remission (disease activity index=0). Twenty-seven (49%) improved, with a final disease activity index of < or = 3 or a four-point reduction. Improvement or normalization in each category of the disease activity index was as follows: stool frequency, 64%; bleeding, 64%; endoscopy, 50%; physicians' rating, 63%. There were no significant relationships between outcome and pharmacokinetics. The most common adverse events were related to the injection site (32.1%).

CONCLUSIONS:

In this pilot study, the tryptase inhibitor APC 2059 was safe and there was evidence of activity in the treatment of ulcerative colitis.

• Authors: W J Tremaine, A Brzezinski, J A Katz, D C Wolf, T J Fleming, J Mordenti, L C Strenkoski-Nix, M C Kurth, AXYS Ulcerative Colitis Study Group
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 16 Issue 3 Pg. 407-13 (Mar 2002) ISSN: 0269-2813 [Print] England
• PMID: 11876693 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Serine Proteinase Inhibitors
• Serine Endopeptidases
• Tryptases

Topics

• Adult
• Aged
• Colitis, Ulcerative (drug therapy)
• Female
• Humans
• Inflammation Mediators (antagonists & inhibitors)
• Male
• Middle Aged
• Pilot Projects
• Serine Endopeptidases (metabolism)
• Serine Proteinase Inhibitors (adverse effects, pharmacology, therapeutic use)
• Tryptases