Randomized placebo-controlled trial of the bradykinin B₂ receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial.

Abstract

BACKGROUND:

The For Angioedema Subcutaneous Treatment (FAST)-3 study was a phase III, randomized, double-blind, placebo-controlled study of icatibant (bradykinin B(2) receptor antagonist) in subjects with hereditary angioedema (HAE) resulting from C1-INH deficiency or dysfunction (type I/II).

OBJECTIVE:

To investigate icatibant efficacy and safety in subjects with acute HAE attacks.

METHODS:

Subjects with moderate to very severe cutaneous or abdominal symptoms received icatibant (n = 43) or placebo (n = 45). Five subjects with laryngeal (mild-to-moderate) first attacks received icatibant (n = 3) or placebo (n = 2), and 5 subjects with severe laryngeal first attacks received open-label icatibant.

RESULTS:

Cutaneous or abdominal attacks: icatibant significantly reduced median times (vs placebo) to 50% or more reduction in symptom severity (2.0 vs 19.8 hours; P < .001, primary endpoint), onset of primary symptom relief (1.5 vs 18.5 hours; P < .001, key secondary endpoint), or almost complete symptom relief (8.0 vs 36.0 hours; P = .012) and provided a shorter time to initial symptom relief (0.8 vs 3.5 hours; P < .001). For laryngeal attacks, median time to 50% or more reduction in symptom severity was 2.5 hours (icatibant) and 3.2 hours (placebo). No icatibant-treated subject required rescue medication before symptom relief occurred. The incidence of adverse events (AEs) was similar in icatibant- and placebo-treated subjects (41% and 52%, respectively). All icatibant-treated subjects experienced injection site reactions, but none reported clinically relevant changes in safety parameters or serious AEs.

CONCLUSIONS:

FAST-3 demonstrated that icatibant was effective and generally well tolerated in subjects with acute HAE attacks.

TRIAL REGISTRATION:

Clinicaltrials.gov Identifier: NCT00912093.

• Authors: William R Lumry, H Henry Li, Robyn J Levy, Paul C Potter, Henriette Farkas, Dumitru Moldovan, Marc Riedl, Hongbin Li, Timothy Craig, Bradley J Bloom, Avner Reshef
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 107 Issue 6 Pg. 529-37 (Dec 2011) ISSN: 1534-4436 [Electronic] United States
• PMID: 22123383 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Bradykinin B2 Receptor Antagonists
• icatibant
• Bradykinin

Topics

• Adult
• Angioedemas, Hereditary (drug therapy)
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
• Bradykinin (administration & dosage, analogs & derivatives)
• Bradykinin B2 Receptor Antagonists
• Double-Blind Method
• Female
• Humans
• Injections, Subcutaneous
• Kaplan-Meier Estimate
• Male