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North ML, Walker TJ, Steacy LM, et al. Add-on histamine receptor-3 antagonist for allergic rhinitis: a double blind randomized crossover trial using the environmental exposure unit. Allergy Asthma Clin Immunol. 2014;10(1):33doi: 10.1186/1710-1492-10-33.
North, M. L., Walker, T. J., Steacy, L. M., Hobsbawn, B. G., Allan, R. J., Hackman, F., Sun, X., Day, A. G., & Ellis, A. K. (2014). Add-on histamine receptor-3 antagonist for allergic rhinitis: a double blind randomized crossover trial using the environmental exposure unit. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 10(1), 33. https://doi.org/10.1186/1710-1492-10-33
North, Michelle L, et al. "Add-on histamine receptor-3 antagonist for allergic rhinitis: a double blind randomized crossover trial using the environmental exposure unit." Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology vol. 10,1 (2014): 33. doi: https://doi.org/10.1186/1710-1492-10-33
North ML, Walker TJ, Steacy LM, Hobsbawn BG, Allan RJ, Hackman F, Sun X, Day AG, Ellis AK. Add-on histamine receptor-3 antagonist for allergic rhinitis: a double blind randomized crossover trial using the environmental exposure unit. Allergy Asthma Clin Immunol. 2014 Jul 03;10(1):33. doi: 10.1186/1710-1492-10-33. eCollection 2014. PMID: 25024716; PMCID: PMC4094756.
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Allergy Asthma Clin Immunol. 2014 Jul 03;10(1):33. doi: 10.1186/1710-1492-10-33. eCollection 2014.

Add-on histamine receptor-3 antagonist for allergic rhinitis: a double blind randomized crossover trial using the environmental exposure unit.

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology

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

Affiliations

  1. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada ; Allergy Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.
  2. Allergy Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.
  3. Pfizer Ltd., Sandwich, UK.
  4. Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada.
  5. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada ; Allergy Research Unit, Kingston General Hospital, Kingston, Ontario, Canada ; Division of Allergy and Immunology, Department of Medicine, Queen's University, Doran 1, Kingston General Hospital, 76 Stuart Street, Kingston, ON K7L 2 V7, Canada.

PMID: 25024716 PMCID: PMC4094756 DOI: 10.1186/1710-1492-10-33

Abstract

BACKGROUND: Oral antihistamines that target the histamine receptor-1, such as fexofenadine, offer suboptimal relief of allergic rhinitis-associated nasal congestion. Combinations with oral sympathomimetics, such as pseudoephedrine, relieve congestion but produce side effects. Previous animal and human studies with histamine receptor-3 antagonists, such as PF-03654764, demonstrate promise.

METHODS: Herein we employ the Environmental Exposure Unit (EEU) to conduct the first randomized controlled trial of PF-03654764 in allergic rhinitis. 64 participants were randomized in a double-blind, placebo-controlled 4-period crossover study. Participants were exposed to ragweed pollen for 6 hours post-dose in the EEU. The primary objective was to compare the effect of PF-03654764 + fexofenadine to pseudoephedrine + fexofenadine on the subjective measures of congestion and Total Nasal Symptom Score (TNSS). The objectives of our post-hoc analyses were to compare all treatments to placebo and determine the onset of action (OA). This trial was registered at ClinicalTrials.gov (NCT01033396).

RESULTS: PF-03654764 + fexofenadine was not superior to pseudoephedrine + fexofenadine. In post-hoc analyses, PF-03654764 + fexofenadine significantly reduced TNSS, relative to placebo, and OA was 60 minutes. Pseudoephedrine + fexofenadine significantly reduced congestion and TNSS, relative to placebo, with OA of 60 and 30 minutes, respectively. Although this study was not powered for a statistical analysis of safety, it was noted that all PF-03654764-treated groups experienced an elevated incidence of adverse events.

CONCLUSIONS: PF-03654764 + fexofenadine failed to provide superior relief of allergic rhinitis-associated nasal symptoms upon exposure to ragweed pollen compared to fexofenadine + pseudoephedrine. However, in post-hoc analyses, PF-03654764 + fexofenadine improved TNSS compared to placebo. Side effects in the PF-03654764-treated groups were clinically significant compared to the controls.

Keywords: Allergic rhinitis; Decongestant; Environmental exposure unit; Fexofenadine; H1 receptor; H3 receptor; Nasal congestion; PF-03654764; Ragweed; pseudoephedrine

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