BACKGROUND:Nasal H(3) receptors might have a role in mediating the effects of histamine in patients with allergic rhinitis. OBJECTIVE: This study explored the effect of the potent oral H(3) receptor antagonist PF-03654746 in combination with an oral H(1) receptor antagonist on the objective (acoustic rhinometry) and subjective (symptoms) responses to nasal allergen challenge. METHODS:Twenty patients with out-of-season allergic rhinitis displaying a 30% or greater decrease inminimum nasal cross-sectional area (A(min)) after bolus (ragweed) complete nasal allergen challenge at screening were studied by using a randomized, double-blind, single-dose, 4-way crossover design. Treatments included 10 mg of PF-03654746 plus 60 mg of fexofenadine (group 1), 1 mg of PF-03654746 plus 60 mg of fexofenadine (group 2), 60 mg of fexofenadine/120 mg of pseudoephedrine (group 3), and placebo (group 4). After dosing, subjects underwent complete nasal allergen challenge. Nasal symptom scores (no. of sneezes and 0- to 5-point scores for severity of congestion, itching, and rhinorrhea), A(min) (in square centimeters), and nasal volume (in cubic centimeters) were recorded 15, 30, 45, and 60 minutes after allergen. There was a minimum 10-day washout between periods. RESULTS: The following symptom scores were significantly (P ≤ .05) reduced by active treatments versus placebo: group 1, congestion of -0.7 (SE, 0.3), itching of -1.0 (SE, 0.3), rhinorrhea of -1.3 (SE, 0.3), and sneeze of -8.8 (SE, 1.5); group 2, itching of -0.6 (SE, 0.3), rhinorrhea of -0.8 (SE, 0.3), and sneeze of -9.1 (SE, 1.5); and group 3, rhinorrhea of -0.7 (SE, 0.3) and sneeze of -7.0 (SE, 1.5). There was no significant effect of any treatment on mean A(min) proportion or nasal volume proportion after nasal allergen challenge. CONCLUSIONS: In combination with fexofenadine, single doses of PF-03654746 caused a reduction in allergen-induced nasal symptoms. H(3) receptor antagonism might be a novel therapeutic strategy to further explore in patients with allergic rhinitis.
RCT Entities:
BACKGROUND: Nasal H(3) receptors might have a role in mediating the effects of histamine in patients with allergic rhinitis. OBJECTIVE: This study explored the effect of the potent oral H(3) receptor antagonist PF-03654746 in combination with an oral H(1) receptor antagonist on the objective (acoustic rhinometry) and subjective (symptoms) responses to nasal allergen challenge. METHODS: Twenty patients with out-of-season allergic rhinitis displaying a 30% or greater decrease in minimum nasal cross-sectional area (A(min)) after bolus (ragweed) complete nasal allergen challenge at screening were studied by using a randomized, double-blind, single-dose, 4-way crossover design. Treatments included 10 mg of PF-03654746 plus 60 mg of fexofenadine (group 1), 1 mg of PF-03654746 plus 60 mg of fexofenadine (group 2), 60 mg of fexofenadine/120 mg of pseudoephedrine (group 3), and placebo (group 4). After dosing, subjects underwent complete nasal allergen challenge. Nasal symptom scores (no. of sneezes and 0- to 5-point scores for severity of congestion, itching, and rhinorrhea), A(min) (in square centimeters), and nasal volume (in cubic centimeters) were recorded 15, 30, 45, and 60 minutes after allergen. There was a minimum 10-day washout between periods. RESULTS: The following symptom scores were significantly (P ≤ .05) reduced by active treatments versus placebo: group 1, congestion of -0.7 (SE, 0.3), itching of -1.0 (SE, 0.3), rhinorrhea of -1.3 (SE, 0.3), and sneeze of -8.8 (SE, 1.5); group 2, itching of -0.6 (SE, 0.3), rhinorrhea of -0.8 (SE, 0.3), and sneeze of -9.1 (SE, 1.5); and group 3, rhinorrhea of -0.7 (SE, 0.3) and sneeze of -7.0 (SE, 1.5). There was no significant effect of any treatment on mean A(min) proportion or nasal volume proportion after nasal allergen challenge. CONCLUSIONS: In combination with fexofenadine, single doses of PF-03654746 caused a reduction in allergen-induced nasal symptoms. H(3) receptor antagonism might be a novel therapeutic strategy to further explore in patients with allergic rhinitis.
Authors: Pertti Panula; Paul L Chazot; Marlon Cowart; Ralf Gutzmer; Rob Leurs; Wai L S Liu; Holger Stark; Robin L Thurmond; Helmut L Haas Journal: Pharmacol Rev Date: 2015-07 Impact factor: 25.468
Authors: Michelle L North; Terry J Walker; Lisa M Steacy; Barnaby G Hobsbawn; Richard J Allan; Frances Hackman; Xiaoqun Sun; Andrew G Day; Anne K Ellis Journal: Allergy Asthma Clin Immunol Date: 2014-07-03 Impact factor: 3.406