A proof-of-concept study of the effect of a novel H3-receptor antagonist in allergen-induced nasal congestion
Open accessAbstract
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.
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Numerous randomized, placebo-controlled clinical trials using allergen challenge chambers have tested the efficacy of drugs with immediate therapeutic activity, such as antihistamines, or with prophylactic therapeutic potential, such as topical steroids, novel anti-inflammatory compounds, or probiotics.
“In this respect, numerous randomized, placebo-controlled clinical trials have been conducted using parallel-group or crossover designs in order to test the efficacy of drugs with immediate therapeutic activity, such as antihistamines,1050-1053 or with prophylactic therapeutic potential, such as topical steroids,1054-1056 novel anti-inflammatory compounds,1057-1060 or probiotics.1061”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [1051]
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BindingDB Entry 50010103: Biphenyloxy-alkyl-piperidine and azepane derivatives as histamine H
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- Authors
- Barchuk, W. T., Salapatek, A. M., Ge, T., D'Angelo, P., & Liu, X.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Barchuk, William T.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 132
- Issue
- 4
- Pages
- 838-846.e6
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W1965728279
- Cited by
- 31
- References
- 29
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 7 · 2015: 5 · 2014: 3 · 2013: 1
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Keywords
- histamine H3 receptor antagonists, nasal congestion, allergic rhinitis, ragweed allergy, allergen exposure, pseudoephedrine, nasal patency, acoustic rhinometry, Total Nasal Symptom Score
- MeSH terms
- Adolescent, Adult, Aged, Allergens, Azepines, Female, Rhinitis, Allergic, Seasonal, Humans, Male, Middle Aged, Pyridines, Sneezing, Nasal Obstruction, Treatment Outcome, Cross-Over Studies, Rhinometry, Acoustic, Ambrosia, Histamine H3 Antagonists, Young Adult
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