title: Tolerability during double-blind randomized phase I trials with the house dust mite allergy immunotherapy tablet in adults and children.
abstract: OBJECTIVE
  The orodispersible house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) is being developed for the treatment of HDM respiratory allergic disease. The objective of the 2 phase I trials was to investigate tolerability and the acceptable dose range of HDM SLIT-tablet treatment in adults and children with HDM respiratory allergic disease.
  
  
  METHODS
  The trials were randomized, multiple-dose, dose-escalation, double-blind, placebo-controlled phase I trials including patients with HDM-induced asthma, with or without rhinoconjunctivitis. Both trials were registered in EudraCT (Trial 1: 2005-002151-41; Trial 2: 2007-000402-67). Trial 1 included 71 adults (18-63 years) and trial 2 included 72 children (5-14 years). Both trials included 6 dose groups that were randomized 3:1 to active treatment or placebo once daily for 28 days. Adverse events (AEs) were coded in MedDRA (version 8.1 or later). Immunological variables included specific IgE and IgE-blocking factor.
  
  
  RESULTS
  No serious AEs were reported. In trial 1 (maximum dose, 32 development units [DU]), 1 patient in the 16 DU group discontinued due to AEs. The entire 32 DU group was discontinued as 1 patient had a severe adverse reaction. In trial 2 (maximum dose, 12 DU), no patients discontinued prematurely. The most frequently reported AEs were mild application-site related events. The total number of events was dose-related within each trial. HDM SLIT-tablet treatment induced changes in immunological parameters in a dose-dependent manner.
  
  
  CONCLUSIONS
  These trials demonstrate that doses up to 12 DU of HDM SLIT-tablet were tolerated in the selected populations, and thus are suitable for further clinical investigations in adults and children with HDM respiratory allergic disease.
authors.forename: J L
authors.initials: JL
authors.lastname: Corzo
authors.forename: T
authors.initials: T
authors.lastname: Carrillo
authors.forename: C
authors.initials: C
authors.lastname: Pedemonte
authors.forename: A M
authors.initials: AM
authors.lastname: Plaza Martin
authors.forename: S
authors.initials: S
authors.lastname: Martín Hurtado
authors.forename: E
authors.initials: E
authors.lastname: Dige
authors.forename: M A
authors.initials: MA
authors.lastname: Calderon
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010808:Physical Examination; D039981:Pyroglyphidae / Q000276:immunology*; D063729:Sublingual Immunotherapy / Q000009:adverse effects*; D013607:Tablets
chemical_list: D013607:Tablets