The effects of an H3 receptor antagonist (PF-03654746) with fexofenadine on reducing allergic rhinitis symptoms

• Published in: Journal of allergy and clinical immunology 2012-02, Vol.129 (2), p.409-412.e2
• Main Authors: Stokes, Jeffrey R., MD, Romero, Francisco A., MS, Allan, Richard J., BSc, Phillips, Peter G., MD, Hackman, Frances, BSc, Misfeldt, Janie, MA, Casale, Thomas B., MD
• Format: Article
• Language: English
• Subjects: Adult; allergic rhinitis; Allergy and Immunology; Ambrosia - immunology; Anti-Allergic Agents - adverse effects; Anti-Allergic Agents - therapeutic use; Biological and medical sciences; Cross-Over Studies; Cyclobutanes - adverse effects; Cyclobutanes - therapeutic use; decongestant; Double-Blind Method; Drug Combinations; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; H3 receptor antagonist; Histamine H1 Antagonists, Non-Sedating - adverse effects; Histamine H1 Antagonists, Non-Sedating - therapeutic use; Histamine H3 Antagonists - adverse effects; Histamine H3 Antagonists - therapeutic use; Humans; Immunopathology; Male; Medical sciences; Middle Aged; nasal congestion; Nasal Provocation Tests; Non tumoral diseases; Otorhinolaryngology. Stomatology; Pyrrolidines - adverse effects; Pyrrolidines - therapeutic use; Rhinitis, Allergic, Seasonal - drug therapy; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin Tests; Terfenadine - adverse effects; Terfenadine - analogs & derivatives; Terfenadine - therapeutic use; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Young Adult
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2011.11.026

Background Nasal H3 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 H3 receptor antagonist PF-03654746 in combination with an oral H1 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 (Amin ) 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), Amin (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 Amin 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. H3 receptor antagonism might be a novel therapeutic strategy to further explore in patients with allergic rhinitis.