Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial.

Abstract

BACKGROUND:

Alicaforsen is an antisense oligonucleotide inhibitor of intercellular adhesion molecule 1 protein expression with activity in subjects with ulcerative colitis and pouchitis.

AIM:

To compare the effects of alicaforsen enema to standard of care mesalazine (mesalamine) enema in subjects with mild to moderate active left-sided ulcerative colitis.

METHOD:

A randomized, double-blind, active-controlled multicentre clinical trial. Subjects received a nightly enema of 120 mg alicaforsen (n=55), 240 mg alicaforsen (n=50), or 4 g mesalazine (n=54) for 6 weeks, followed by a 24-week monitoring period. The primary end point was Disease Activity Index at week 6. Clinical improvement, remission and relapse were secondary end points.

RESULTS:

No significant difference was observed between treatment arms in the primary end point. However, the median duration of response to alicaforsen enema treatment was two- to threefold longer (128 and 146 days) in comparison with mesalazine (54 days). Complete mucosal healing occurred in 24% of the 240 mg alicaforsen group, when compared with 17% in the mesalazine.

CONCLUSIONS:

Alicaforsen enema demonstrated an acute response and safety profile similar to mesalazine enema, but was differentiated by a more durable response. The extended length of remission suggests that alicaforsen enema treatment may have a disease modifying effect.

• Authors: P B Miner Jr, M K Wedel, S Xia, B F Baker
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 23 Issue 10 Pg. 1403-13 (May 15 2006) ISSN: 0269-2813 [Print] England
• PMID: 16669955 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Gastrointestinal Agents
• Oligodeoxyribonucleotides, Antisense
• Phosphorothioate Oligonucleotides
• Thionucleotides
• Mesalamine
• alicaforsen

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, adverse effects)
• Colitis, Ulcerative (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Enema
• Female
• Gastrointestinal Agents (administration & dosage, adverse effects)
• Gastrointestinal Diseases (chemically induced)
• Humans
• Male
• Mesalamine (administration & dosage, adverse effects)
• Middle Aged
• Oligodeoxyribonucleotides, Antisense (administration & dosage, adverse effects)
• Phosphorothioate Oligonucleotides
• Thionucleotides (administration & dosage, adverse effects)
• Treatment Outcome