Low-dose brimonidine for relief of ocular redness: integrated analysis of four clinical trials.

BACKGROUND: The aim of this study was to provide an integrated analysis of safety and efficacy data for brimonidine tartrate ophthalmic solution 0.025 per cent (low-dose; Bausch & Lomb Incorporated), a topical vasoconstrictor for relief of ocular redness. METHODS: Integrated efficacy data from two randomised, double-masked, vehicle-controlled studies in subjects with ocular redness as well as safety data from the two efficacy studies, a vehicle-controlled safety study, and a pharmacokinetic study were analysed. Efficacy outcomes analysed included investigator-assessed ocular redness (scale, 0-4) before treatment instillation and at five to 240 minutes post-instillation on Day 1, at five minutes post-instillation on Days 15 and 29, and one week after treatment discontinuation (Day 36), and redness self-assessed by subjects recorded daily in diaries. Safety assessments included adverse events, ophthalmic examinations, and rebound redness upon treatment discontinuation. Drop comfort (scale, 0-10) was a tolerability measure. RESULTS: The efficacy population included 117 subjects (brimonidine, n = 78; vehicle, n = 39). The safety population included 635 subjects (brimonidine, n = 426; vehicle, n = 209). Investigator-assessed ocular redness was significantly lower with brimonidine versus vehicle at all post-instillation time points on Day 1 (mean change from pre-instillation of -1.4 units for brimonidine and -0.2 units for vehicle; p < 0.0001). Subject-assessed ocular redness was also significantly lower with brimonidine versus vehicle (mean treatment difference in average daily ratings of -0.9; p < 0.0001). There was no evidence of tachyphylaxis through Day 29 and rebound redness was rare. Incidence of ocular adverse events was low, the most common being reduced visual acuity (brimonidine, 4.0 per cent; vehicle, 4.3 per cent) and conjunctival hyperaemia (2.6 and 2.9 per cent, respectively). Both brimonidine and vehicle were rated as very comfortable (mean post-instillation scores, 0.4-0.5). CONCLUSION: In this integrated analysis, low-dose brimonidine significantly reduced ocular redness with no tachyphylaxis, and minimal rebound redness, and was generally safe and well tolerated.

Effect of alcaftadine 0.25% on ocular itch associated with seasonal or perennial allergic conjunctivitis: a pooled analysis of two multicenter randomized clinical trials.

PURPOSE: Seasonal and perennial allergic conjunctivitis represent the majority of cases of ocular allergy. This analysis was designed to evaluate the efficacy and safety of once-daily alcaftadine 0.25% in preventing ocular itching associated with seasonal or perennial allergic conjunctivitis. SUBJECTS AND METHODS: Pooled data from two double-masked, multicenter, placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis were analyzed. Subjects randomized to receive treatment with alcaftadine 0.25% or placebo were challenged with seasonal (grass, ragweed, trees) or perennial (cat dander, cat hair, dog dander, dust mites, cockroach) allergens, 16 hours after treatment instillation. The primary efficacy measure was subject-evaluated mean ocular itching at 3 minutes post-CAC. Secondary measures included ocular itching at 5 and 7 minutes post-CAC. The proportion of subjects with minimal itch (itch score <1) and zero itch (itch score =0), and safety were also assessed. RESULTS: A total of 189 subjects enrolled in the two studies were treated with alcaftadine or placebo. Overall, 129 subjects were challenged with seasonal allergens and 60 subjects were challenged with perennial allergens. Alcaftadine 0.25% achieved a statistically significant reduction in mean itch score at 3, 5, and 7 minutes post-CAC compared with placebo in subjects challenged with seasonal allergens (P<0.0001 at all time points) and those challenged with perennial allergens (P<0.0001 at all time points). A higher percentage of subjects treated with alcaftadine compared with placebo achieved minimal itch (P≤0.001 versus placebo at all time points) and zero itch (P<0.05 at all time points except 7 minutes for perennial) when challenged with either seasonal or perennial allergens. No treatment-related or serious adverse events were reported. CONCLUSION: Once-daily alcaftadine 0.25% ophthalmic solution was well tolerated and demonstrated effective relief of ocular itching in subjects challenged with allergens classic for triggering either seasonal or perennial allergic conjunctivitis.

Ocular itch relief with alcaftadine 0.25% versus olopatadine 0.2% in allergic conjunctivitis: pooled analysis of two multicenter randomized clinical trials.

INTRODUCTION: The efficacy and safety of the once-daily topical ophthalmic solutions, alcaftadine 0.25% and olopatadine 0.2%, in preventing ocular itching associated with allergic conjunctivitis were evaluated. METHODS: Pooled analysis was conducted of two double-masked, multicenter, active- and placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Subjects were randomized 1:1:1 to receive alcaftadine 0.25%, olopatadine 0.2%, or placebo. The primary efficacy measure was subject-evaluated mean ocular itching at 3 min post-CAC and 16 h after treatment instillation. Secondary measures included ocular itching at 5 and 7 min post-CAC. Ocular itch was determined over all time points measured (3, 5, and 7 min) post-CAC and the proportion of subjects with minimal itch (itch score<1) and zero itch (itch score=0) was also assessed. RESULTS: A total of 284 subjects were enrolled in the two studies. At 3 min post-CAC and 16 h after treatment instillation, alcaftadine 0.25% achieved a significantly lower mean itch score compared with olopatadine 0.2% (0.50 vs. 0.87, respectively; P=0.0006). Alcaftadine demonstrated a significantly lower mean itch score over all time points compared with olopatadine (0.68 vs. 0.92, respectively; P=0.0390); both alcaftadine- and olopatadine-treated subjects achieved significantly lower overall mean ocular itching scores compared with placebo (2.10; P<0.0001 for both actives). Minimal itch over all time points was reported by 76.1% of alcaftadine-treated subjects compared with 58.1% of olopatadine-treated subjects (P=0.0121). Treatment with alcaftadine 0.25% and olopatadine 0.2% was safe and well tolerated; no serious adverse events were reported. CONCLUSION: Once-daily alcaftadine 0.25% ophthalmic solution demonstrated greater efficacy in prevention of ocular itching compared with olopatadine 0.2% at 3 min post-CAC (primary endpoint), and over all time points, 16 h post-treatment instillation. Alcaftadine and olopatadine both provided effective relief compared with placebo and were generally well tolerated.