JL Corzo,1 T Carrillo,2
C Pedemonte,3 AM Plaza Martín,4 S
Martin Hurtado,5 E Dige,6 MA
Calderon7 |
1Hospital Materno Infantil,
Malaga, Spain
2Hospital Dr. Negrín, Las Palmas, Spain
3Hospital de Nens, Barcelona, Spain
4Hospital Sant Joan de Deu, Barcelona, Spain
5Medical Department, ALK, Madrid, Spain
6Global Clinical Development, ALK, Hørsholm,
Denmark
7Imperial College London, NHLI, Royal
Brompton Hospital, London, UK |
Abstract |
Background and
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.
Patients and
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.
Key words:
Sublingual
immunotherapy
tablet. House dust
mite.
Placebo-controlled.
Sublingual
Immunotherapy. Phase
I. |
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