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

Aliment Pharmacol Ther. 2006 May 15;23(10):1403-13. doi: 10.1111/j.1365-2036.2006.02837.x.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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