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

Allergy, Asthma & Clinical Immunology

Michelle L North²  Terry J Walker²  Lisa M Steacy²  Barnaby G Hobsbawn²  Richard J Allan¹  Frances Hackman¹  Xiaoqun Sun⁴  Andrew G Day⁴  Anne K Ellis³ 

[1] Pfizer Ltd., Sandwich, UK

[2] Allergy Research Unit, Kingston General Hospital, Kingston, Ontario, Canada

[3] 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

[4] Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada

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

Others  :  1082145
DOI  :  10.1186/1710-1492-10-33

 received in 2014-04-17, accepted in 2014-06-15,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 North et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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