title: 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.
  
  
  BACKGROUND
  Clinicaltrials.gov Identifier: NCT00912093.
authors: Allergy and Asthma Research Associates Research Center, Dallas, Texas 75081, USA. LumryMD@AllergySpecialists.us
authors: William R
authors: WR
authors: Lumry
authors: H Henry
authors: HH
authors: Li
authors: Robyn J
authors: RJ
authors: Levy
authors: Paul C
authors: PC
authors: Potter
authors: Henriette
authors: H
authors: Farkas
authors: Dumitru
authors: D
authors: Moldovan
authors: Marc
authors: M
authors: Riedl
authors: Hongbin
authors: H
authors: Li
authors: Timothy
authors: T
authors: Craig
authors: Bradley J
authors: BJ
authors: Bloom
authors: Avner
authors: A
authors: Reshef
mesh_terms: D000328:Adult; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D065094:Bradykinin B2 Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D053208:Kaplan-Meier Estimate; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065094:Bradykinin B2 Receptor Antagonists; C065679:icatibant; D001920:Bradykinin