Safety of cetirizine ophthalmic solution 0.24% for the treatment of allergic conjunctivitis in adult and pediatric subjects

Abstract

Purpose: The studies reported here aimed to assess the safety and tolerability of cetirizine ophthalmic solution 0.24%, a new topical ophthalmic medication approved by the US Food and Drug Administration for the treatment of ocular itching associated with allergic conjunctivitis.

Patients and methods: Three clinical studies evaluated cetirizine ophthalmic solution 0.24% administration: a Phase I prospective, single-center, open-label, pharmacokinetic (PK) study (N=11) evaluating single-dose administration and twice-daily (BID) administration for 1 week in healthy adults, and two Phase III, multi-center, randomized, double-masked, vehicle-controlled, parallel-group studies evaluating the safety and tolerability in adult and pediatric populations (2-18 years of age) for up to 6 consecutive weeks. The first safety and tolerability study evaluated cetirizine BID (study 1, N=512), while the second study examined cetirizine three times daily (TID) (study 2, N=516). Each study assessed best corrected visual acuity, slit-lamp biomicroscopy, IOP, dilated ophthalmoscopy, treatment-emergent adverse events, vital signs, urine pregnancy test, and physical examination (general health, head, eyes, ears, nose, and throat). The PK study also measured hematology, blood chemistry, and urinalysis, while the two Phase III studies additionally assessed corneal endothelial cell counts (ECC) and ECC density in a subset of subjects (via specular microscopy), and drug administration tolerability.

Results: Bilateral administration of cetirizine ophthalmic solution 0.24% resulted in low systemic exposure in the PK study and was associated with a low incidence of mild adverse events. There were no drug-related severe or serious adverse events. The tolerability scores between the active and vehicle groups were comparable, demonstrating high comfort in the administration of cetirizine ophthalmic solution 0.24%.

Conclusion: Cetirizine ophthalmic solution 0.24% dosed BID or TID demonstrated an acceptable safety profile and was well-tolerated when administered to subjects aged ≥2 years.

Keywords: antihistamine; ocular allergy; ocular itching; tolerability; topical administration.

Figure 1

Cetirizine plasma concentration by visit, PK study. Notes: Eleven subjects were enrolled in the study and ten subjects completed the PK study. One subject was withdrawn from the study because of lack of venous access. Error bars represent one standard error on each side. Time 0 is from the pre-instillation score at visit 2. Abbreviations: BID, twice daily; PK, pharmacodynamics.

Figure 2

Cetirizine drop comfort. Notes: The tolerability measure of drop comfort assessment was performed at visits 1, 2, and 3. Subjects self-assessed the comfort of either study drug or vehicle instillation (“drop comfort”) for both eyes (OU) at three time points: immediately upon instillation, 30 seconds post-dose, and 1 minute post-dose. Subjects graded drop comfort by selecting a value on numerical scale ranging from 0 to 10, wherein 0=very comfortable and 10=very uncomfortable; therefore, a lower score indicated greater comfort. (A) BID study 1 (N=512) and (B) TID study 2 (N=516). Data shown are the mean and standard error of the mean. Abbreviations: BID, twice daily (study 1); TID, three times daily (study 2).