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

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.Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Available from: http://www.annallergy.org/article/S1081-1206%2811%2900658-2/fulltext