Original article
Interventions
Efficacy of epinastine hydrochloride ophthalmic solution in allergic conjunctivitis by conjunctival cedar pollen allergen challenge

https://doi.org/10.1016/j.anai.2014.07.007Get rights and content

Abstract

Background

Epinastine hydrochloride is a selective histamine H1 receptor antagonist that also inhibits IgE receptor-mediated histamine release from mast cells.

Objective

To show the superiority of epinastine 0.05% ophthalmic solution (epinastine) to placebo ophthalmic solution (placebo) and noninferiority to olopatadine 0.1% ophthalmic solution (olopatadine) for cedar pollen antigen-induced ocular itching and conjunctival hyperemia.

Methods

The study was conducted in ophthalmologically asymptomatic adult volunteers with seasonal allergic conjunctivitis using a conjunctival allergen challenge test. Subjects were randomized into 3 groups (n = 87) to evaluate superiority to placebo (visits 4 to 6) and 2 groups (n = 86) to evaluate noninferiority to olopatadine (visit 7). At each visit, a single administration of the study medication was instilled at 15 minutes (visit 4), 4 hours (visit 5), 8 hours (visit 6), and 4 hours (visit 7) before the conjunctival allergen challenge test. Ocular itching and conjunctival hyperemia of allergic conjunctivitis were assessed after the conjunctival allergen challenge test.

Results

For the primary end point, epinastine showed superiority to placebo for the inhibition of ocular itching and conjunctival hyperemia induced at 4 hours after the dose (equivalent to 4-times-daily dosing). For the secondary end points, epinastine significantly inhibited itching and conjunctival hyperemia induced at 15 minutes and 8 hours after the dose (equivalent to 2-times-daily dosing) compared with placebo. In addition, epinastine demonstrated noninferiority to olopatadine for ocular itching and conjunctival hyperemia. No adverse drug reactions or serious adverse events were reported throughout the study, indicating that epinastine has a good safety profile.

Conclusion

Epinastine is effective and safe for the treatment of allergic conjunctivitis.

Trial Registration

Clinicaltrials.gov identifier NCT01363700.

Introduction

Seasonal allergic conjunctivitis is the most common allergic disease and affects millions of people worldwide. Regarding the underlying mechanism, degranulation of mast cells leads to the local release of inflammatory chemical mediators in the conjunctiva.1 In this regard, the roles of mast cell stabilizers and H1 blockers as topical therapeutic regimens have been extensively explored for the past 2 decades.

In general, environmental and conjunctival allergen challenge (CAC) studies are performed primarily for the clinical evaluation of antiallergic ophthalmic solutions. In environmental studies, the efficacy of antiallergic ophthalmic solutions has been evaluated in trials using natural exposure, such as during the pollen season. However, that model has an inherent drawback of different exposures between seasons and individuals.2 Conversely, CAC studies use a defined exposure that can be adjusted for individuals with regard to the allergen exposure rate.[2], [3], [4], [5] As models that allow for appropriate clinical assessment of allergic conjunctivitis, CAC studies have been used in the United States, Europe, Japan, and other countries.[6], [7], [8]

Epinastine hydrochloride is a topical ocular antihistamine that exhibits strong binding to histamine H1 receptors and has potent anti-inflammatory properties resulting from the inhibition of the release of mediators, such as histamine and leukotriene, and the decrease of the downstream effects of leukotriene C4, platelet-activating factor, serotonin, and other factors.[9], [10], [11], [12] The authors conducted a phase III CAC study of epinastine hydrochloride 0.05% ophthalmic solution (epinastine) using an allergen solution of cedar pollen, the most widely dispersed pollen species in Japan.

Section snippets

Subjects

Adult volunteers with a history of seasonal allergic conjunctivitis and cedar pollen-specific IgE were selected. Subjects had to be asymptomatic, with no ocular itching or conjunctival hyperemia, before the allergen challenge. The main exclusion criteria included complications of extraocular or anterior ocular segment inflammatory disease or dry eye, a Schirmer test reaction no larger than 5 mm, recent (<90 days) intraocular surgery, or recent (<30 days) treatment for lacrimal punctum

Baseline Characteristics

Table 2 lists the baseline characteristics of the subjects in the full analysis set. One subject in group B (Epi/Epi) was withdrawn from the study after the completion of visit 5 because the subject had difficulty with the schedule. There was no intergroup bias in any of the background characteristics.

Ocular itching

The primary end points of the mean ocular itching scores (mean ± SE) for the 3 time points after allergen challenge at 4 hours were 0.4 ± 0.1 and 1.7 ± 0.1 for epinastine and placebo, respectively

Discussion

During the annual cedar pollen season in Japan, many patients develop seasonal allergic conjunctivitis with intense ocular itching and have significant impairment in their quality of life. Although the estimated prevalence of allergic conjunctival disease is approximately 15% to 20%,1 increasing numbers of patients are developing cedar pollinosis, and the disease is a major public health problem in Japan because of its intense symptoms, high prevalence, poor spontaneous recovery rate, and

Acknowledgment

The authors thank the principal investigator, Dr Hiroshi Nakatani at the Kitasato University Kitasato Institute Hospital Biomedical Research Center.

References (20)

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Disclosure: Drs Fujishima, Ohashi, and Takamura have consulted for Santen Pharmaceutical Co Ltd.

Funding: This study was sponsored and funded by Santen Pharmaceutical Co Ltd, Osaka, Japan.

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