Evaluation of the new ophthalmic antihistamine, 0.05% levocabastine, in the clinical allergen challenge model of allergic conjunctivitis

doi:10.1016/0091-6749(94)90201-1

Journal of Allergy and Clinical Immunology

Volume 94, Issue 3, Part 1, September 1994, Pages 458-464

https://doi.org/10.1016/0091-6749(94)90201-1 Get rights and content

Abstract

The objective of this study was to evaluate the efficacy of 0.05% levocabastine, a new antihistamine formulated for ophthalmic use, compared with the placebo vehicle for the treatment of allergic conjunctivitis induced by ocular allergen challenge. Subjects who reacted positively in both eyes on two separate occasions to ocular allergen challenge with grass, ragweed, or cat dander (N = 47) received one dose of 1 to 2 drops of 0.05% levocabastine in one eye and its vehicle in the other eye. After 10 minutes, the predetermined dose of allergen was instilled in both eyes. Signs and symptoms of allergic conjunctivitis were evaluated with biomicroscopy and subjective evaluation of itching after 3, 5, and 10 minutes. Four hours after drug administration, subjects were rechallenged and reevaluated to determine levocabastine's duration of action. Results showed that levocabastine was significantly more effective than placebo in inhibiting itching, hyperemia, eyelid swelling, chemosis, and tearing after the initial challenge and in inhibiting all parameters except eyelid swelling after the rechallenge 4 hours later (p < 0.05). These results demonstrate that levocabastine, currently the only ophthalmic antihistamine available that is not combined with a vasoconstrictor, is efficacious in the inhibition of itching, as well as all of the allergic signs of a vascular origin, with a duration of action of at least 4 hours. Because of its strong effects on itching and hyperemia, chemosis, lid swelling, and tearing, levocabastine would be a valuable therapeutic agent to add to the heterogeneous family of antiallergic compounds presently available for the treatment of seasonal allergic conjunctivitis. (J ALLERGY CLIN IMMUNOL 1994;94:458-64.)

Section snippets

Subjects

All subjects read and signed an Informed Consent agreement approved by the Western Institutional Review Board (Olympia, Wash.) before entering the study. The following inclusion criteria had to be met by each subject: (1) ability and willingness to give consent; (2) ability and willingness to make all study visits; (3) ability to follow instructions; (4) age between 18 and 65 years; (5) successful challenge, inducing a score of at least 2 + in redness and itching in both eyes on two visits

Subject population

At visit 1, 65 subjects were initially challenged with antigen; 58 (89%) responded with a score of at least 2 + in itching and redness in both eyes. At visit 2, 57 of these 58 responders returned for a second challenge. A second positive bilateral allergen challenge response was observed in 48 of the 57 subjects (84%). On day 8, visit 3, all 48 subjects returned for the evaluation of drug efficacy. One subject was not challenged because he had taken a prohibited medication, which may have

DISCUSSION

Seasonal allergic conjunctivitis is a common ocular allergic disease seen by both the allergists and the ophthalmologist. This disease is the clinical result of mast cell degranulation triggered by IgE antibody-antigen interactions on mast cell membranes. Histamine, stored in the granules of mast cells and basophils, is the principle preformed mediator released from mast cells. In more complex and chronic diseases, such as vernal and atopic keratoconjunctivitis, this repetitive mast cell

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^☆: From ^athe Department of Ophthalmology, Harvard Medical School; ^bthe Schepens Eye Research Institute, Boston, and ^cPharmaceutical Development Consulting, Padova, Italy.

^☆☆: Supported in part by a grant from Johnson and Johnson, Iolab Corporation, and in part by a grant from the Harry, Evelyn and John Axelrod Charitable Trust.

^★: Reprint requests: Mark B. Abelson, MD, Schepens Eye Research Institute, 20 Staniford St., Boston, MA 02114.

^★★: 0091-6749/94 $3.00 + 0 1/1/55422

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Evaluation of the new ophthalmic antihistamine, 0.05% levocabastine, in the clinical allergen challenge model of allergic conjunctivitis☆,☆☆,★,★★

Abstract

Section snippets

Subjects

Subject population

DISCUSSION

J ALLERGY CLIN IMMUNOL

J ALLERGY CLIN IMMUNOL

Ophthalmology

Ophthalmology

Ocular allergies

Conjunctival allergen challenge. A clinical approach to studying allergic conjunctivitis

Arch Ophthalmol

Conjunctival provocation tests and naturally occurring allergic conjunctivitis in clinical trials

Int Ophthal Clin

The precision of the conjunctival provocation test

Allergy

Production of leukotrienes in human skin and conjunctival mucosa after specific allergen challenge

Allergy

Cross-reactivity between deciduous trees during immunotherapy. I. In vivo results

Clin Allergy

Local immunotherapy in allergic conjunctivitis

Invest Ophthalmol Vis Sci

Effect of a new selective H 1 receptor antagonist (levocabastine) in a nasal and conjunctival provocation test

Int Arch Allergy Appl Immunol

Effects of Vasocon-A in the allergen challenge model of acute allergic conjunctivitis

Arch Ophthalmol

Cromolyn sodium treatment of seasonal ragweed conjunctivitis

Invest Ophthalmol Vis Sci

Effect of a new selective H ₁ receptor antagonist (levocabastine) in a nasal and conjunctival provocation test