A proof-of-concept study of the effect of a novel H3-receptor antagonist in allergen-induced nasal congestion.
J Allergy Clin Immunol
; 132(4): 838-46.e1-6, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23791513
ABSTRACT
BACKGROUND:
H1-receptor inverse agonists are used effectively for treating several symptoms of allergic rhinitis, including nasal itching, rhinorrhea, and sneezing, although most agents are not very effective in treating nasal congestion.OBJECTIVE:
This study evaluated the relative efficacy of a novel selective H3-receptor antagonist, JNJ-39220675, in preventing nasal congestion induced by exposing participants with ragweed allergy to ragweed allergen in an environmental exposure chamber model.METHODS:
In this single-dose, patient-blind, double-dummy, placebo- and active-controlled, phase IIa cross-over study, 53 participants were randomized to JNJ-39220675 plus placebo, placebo plus pseudoephedrine, or only placebo. The primary efficacy assessment was change in nasal patency assessed by measuring the minimal cross-sectional area of the nasal cavity by using acoustic rhinometry. Secondary assessment included total nasal symptom scores (TNSSs) over the 8-hour environmental exposure chamber exposure period.RESULTS:
Smaller decreases in minimal cross-sectional area were observed after JNJ-39220675 (least square mean difference, -0.126; P = .06) and pseudoephedrine (least square mean difference, -0.195; P = .004) treatment compared with placebo. The means for the baseline-adjusted area under the curve of TNSSs were significantly smaller for JNJ-39220675 (P = .0003) and pseudoephedrine (P = .04) versus placebo. JNJ-39220675 was significantly effective in treating all 4 individual symptoms (P ≤ .05 for all scores) compared with placebo, whereas pseudoephedrine only showed a trend for improvement in individual symptom scores of the TNSS. Insomnia was the most frequent adverse event (17.3%) associated with JNJ-39220675 treatment.CONCLUSION:
Prophylactic treatment with the H3-antagonist JNJ-39220675 relieved allergen-induced nasal congestion by using standard nasal symptom scoring; however, in contrast to pseudoephedrine, it only showed a trend for increasing nasal patency by using objective measures.Palavras-chave
AUC; AcR; Acoustic rhinometry; Allergic rhinitis; Area under the curve; CNS; Central nervous system; ECP; EEC; Environmental exposure chamber; Eosinophil cationic protein; H(3)-receptor antagonist; JNJ-39220675; LSM; Least square mean; MCA; Minimal cross-sectional area; SAR; Seasonal allergic rhinitis; TEAE; TNSS; Total nasal symptom score; Treatment-emergent adverse event; acoustic rhinometry; environmental exposure chamber; pseudoephedrine; total nasal symptom scores
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Azepinas
/
Obstrução Nasal
/
Rinite Alérgica Sazonal
/
Ambrosia
/
Antagonistas dos Receptores Histamínicos H3
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article