Rhinitis, sinusitis, and upper airway diseaseA proof-of-concept study of the effect of a novel H3-receptor antagonist in allergen-induced nasal congestion
Section snippets
Study population
Men and women aged 18 to 65 years (inclusive) with a body mass index of between 18 and 32 kg/m2 (inclusive) and a body weight of 50 kg or greater and in good health were enrolled. Participants were required to have a clinical history of SAR with a seasonal onset and offset of nasal allergy symptoms during each of the last 2 ragweed allergy seasons and a positive skin prick test response to ragweed allergen (defined as a wheal diameter ≥3 mm larger than that elicited by the negative control) or
Participant disposition
The study was conducted from November 10, 2008, to February 8, 2009, at Cetero Research, Mississauga, Ontario, Canada. Of the 147 participants screened, 53 were randomized to one of 6 treatment sequences (Fig 1) and included in the safety and intent-to-treat analysis. The majority (72%) were men and 49% were white, with a mean age of 42 (SD, 12) years (Table I). Four participants discontinued the study (Fig 1).
Efficacy
Carryover effects of active treatments on MCA and nasal symptom scores in periods 2
Discussion
Both JNJ-39220675 and pseudoephedrine resulted in a smaller decrease in the MCA (less of a decrease in nasal patency or less congestion) versus placebo in participants with ragweed allergy exposed to ragweed in an EEC. A statistically significant difference was observed with pseudoephedrine versus placebo in reducing the baseline-adjusted MCA. JNJ-39220675 showed a strong trend in the same direction (P = .06). On the basis of these data, the hypothesis that H3-receptor inhibition would result
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The Pharmacology of Antihistamines
2022, Comprehensive PharmacologyHistamine H<inf>3</inf> receptor antagonists/inverse agonists: Where do they go?
2019, Pharmacology and TherapeuticsIdentification of novel β-lactams and pyrrolidinone derivatives as selective Histamine-3 receptor (H3R) modulators as possible anti-obesity agents
2018, European Journal of Medicinal ChemistryCitation Excerpt :Johnson and Johnson developed a drug Bavisant (JNJ-31001074), a potent and selective brain-penetrating and orally active small molecule H3R antagonist which has been found effective for the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adults [22]. JNJ39220675, another selective histamine H3R antagonist effective for the treatment of seasonal allergic rhinitis was discontinued after Phase 2 clinical trials [23]. MK-0249, a histamine H3 receptor antagonist developed by Merck and Co. underwent clinical trials for the treatment of Alzheimer's disease [NCT-ID NCT00420420, NCT00874939], attention deficit hyperactivity disorder (ADHD)[NCT-ID NCT00475735], obstructive sleep apnea/hypopnea syndrome (OSA/HS)[NCT-ID NCT00620659] and schizophrenia [NCT-ID NCT00506077].
Biphenyloxy-alkyl-piperidine and azepane derivatives as histamine H<inf>3</inf> receptor ligands
2017, Bioorganic and Medicinal ChemistryCitation Excerpt :Intensive works done by academic and pharmaceutical company researchers has led to many potent and selective H3R antagonists/inverse agonists (for review see e.g.2–6). A few compounds have advanced to the clinical area for the potential treatment of human disorders, such as Alzheimer’s Disease (e.g. ABT-288 (1; Fig. 1), GSK239512), ADHD (e.g. bavisant, MK0249), allergic rhinitis (e.g. GSK1004723, PF03654764, JNJ39220675), narcolepsy (e.g. pitolisant, GSK189254), obesity (e.g. SCH497079, HPP404) or schizophrenia (e.g. ABT-288 (1; Fig. 1), GSK239512).6,7 Some of them exhibited wakefulness-promoting effects in humans and efficacy in narcoleptic patients (e.g. pitolisant8) but others were not efficacious in patients suffering from AD (e.g. ABT-288 (1)9 Fig. 1), attention-deficit hyperactivity disorder (e.g. bavisant10), or schizophrenia (e.g. ABT-288 (1)11; Fig. 1).
Cherry-picked ligands at histamine receptor subtypes
2016, NeuropharmacologyNovel, Alternative, and Controversial Therapies of Rhinitis
2016, Immunology and Allergy Clinics of North AmericaCitation Excerpt :A therapeutic role for histamine H3 receptor antagonism in AR has been proposed and may be complementary to the currently used H1-antihistamines.19 Prophylactic treatment with the H3-antagonist JNJ-39220675 relieved allergen-induced nasal congestion by using standard nasal symptom scoring; however, in contrast with pseudoephedrine, it only showed a trend for increasing nasal patency using objective measures.20 The new molecule PF-03654764 is a potent and specific H3 receptor antagonist.
Supported by Janssen Research & Development, LLC (formerly Johnson and Johnson Research and Development, LLC).
Disclosure of potential conflict of interest: W. T. Barchuk is employed by and owns stock/stock options in Janssen Research & Development. A. M. Salapatek and P. D'Angelo have been supported by one or more grants from Cetero Research at the time of the study, which was sponsored by Janssen Research & Development. T. Ge and X. Liu are employed by Janssen Research & Development.