Phase III trials examining the efficacy of cetirizine ophthalmic solution 0.24% compared to vehicle for the treatment of allergic conjunctivitis in the conjunctival allergen challenge model

Abstract

Purpose: The purpose of these Phase III studies was to evaluate the efficacy and safety of cetirizine ophthalmic solution 0.24% compared with vehicle in the treatment of allergen-induced conjunctivitis using the Ora conjunctival allergen challenge (CAC)^® model.

Methods: The single-center (Study 1) and multi-center (Study 2), double-masked, randomized, vehicle-controlled, parallel group, CAC studies were conducted over ~5 weeks and four study visits. The study design only differed in entry criteria: Study 2 required more severe allergic conjunctivitis symptoms. Subjects were screened for an allergen response at Visits 1 and 2 and then randomized at Visit 3. Approximately 100 subjects were randomized in each study. The primary efficacy endpoints were ocular itching and conjunctival redness 15 minutes and 8 hours post-treatment, post-CAC.

Results: Cetirizine treatment administered 15 minutes or 8 hours prior to CAC resulted in significantly lower ocular itching at all time points post-CAC (P<0.0001) compared to vehicle in both studies. Conjunctival redness measured by the investigator was significantly lower after cetirizine treatment compared to vehicle at 7 minutes post-CAC at both 15 minutes and 8 hours post-treatment in both studies (P<0.05). All secondary endpoints were in favor and confirmatory of cetirizine efficacy with significant improvement in chemosis, eyelid swelling, tearing, ciliary redness, and episcleral redness, as well as nasal symptoms (rhinorrhea, nasal pruritus, ear or palatal pruritus, and nasal congestion) post-CAC. The most robust treatment differences were observed in Study 2 where more severe symptoms were required for study entry (P<0.05). No safety concerns for cetirizine ophthalmic solution 0.24% were identified.

Conclusion: Cetirizine ophthalmic solution 0.24% was shown to be efficacious in the treatment of ocular and nasal signs and symptoms associated with allergic conjunctivitis and demonstrated a favorable safety profile. Clinical efficacy was demonstrated with a 15-minute onset of action and añ8-hour duration of action.

Keywords: cetirizine; ocular allergy; ocular itching; safety; topical administration.

Figure 1

Study design. Notes: During the four study visits, evaluations and treatments proceeded as follows: Visit 1 (Day −21±3), screening procedures at Visit 1 determined subject eligibility; Visit 2 (Days −14±3), baseline procedures at Visit 2 confirmed subject eligibility; Visit 3 (Day 0), Visit 3 was divided into two office visits on the same day, such as Visit 3A and Visit 3B. During Visit 3A, eligible subjects who had satisfied the inclusion and exclusion criteria were enrolled into the study, randomized, and received their first dose of either cetirizine ophthalmic solution 0.24% or vehicle (1–2 drops) bilaterally. Visit 3B assessed ocular and nasal signs and symptoms before and after the CAC. Visit 4 (Days 14±3): subjects received their second dose of either cetirizine ophthalmic solution 0.24% or vehicle (1–2 drops). Fifteen minutes after instillation, subjects underwent the bilateral CAC and ocular and nasal signs and symptoms were assessed. Abbreviations: AC, allergic conjunctivitis; CAC, conjunctival allergen challenge.

Figure 2

Ocular itching. Notes: Mean scores of the cetirizine ophthalmic solution 0.24% (blue) and the vehicle (green) group are shown from each study. Data shown are mean and standard error of the mean for each time point (3, 5, or 7 minutes post-CAC) after treatment (15 minutes or 8 hours postdosing). (A) Study 1, n=50 in each treatment group. (B) Study 2, n=51 and 50 in the cetirizine and vehicle treatments, respectively. *P<0.05. Abbreviations: AC, allergic conjunctivitis; CAC, conjunctival allergen challenge; PT, post-treatment.

Figure 3

Eyelid swelling. Notes: Mean scores of the cetirizine ophthalmic solution 0.24% (blue) and the vehicle (green) group are shown from each study. Data shown are mean and standard error of the mean for each time point (7, 15, or 20 minutes post-CAC) after treatment (15 minutes or 8 hours postdosing). (A) Study 1, n=50 in each treatment group. (B) Study 2, n=51 and 50 in the cetirizine and vehicle treatments, respectively. *P<0.05. Abbreviations: AC, allergic conjunctivitis; PT, post-treatment; CAC, conjunctival allergen challenge.