Twice-Daily vs. Once-Daily Dosing with 0.075% Bromfenac in DuraSite: Outcomes from a 14-Day Phase 2 Study

Abstract

IntroductionBromfenac is a well-known topical ophthalmic nonsteroidal anti-inflammatory drug (NSAID) that is commercialized in the USA and other regions of the world. A new formulation, 0.075% bromfenac in DuraSite®, was developed to treat postoperative inflammation and reduce pain in patients who have undergone cataract surgery. We hypothesized that efficacy and safety would be enhanced with twice-daily (BID) dosing compared to once-daily (QD) dosing.MethodsThis was a multicenter, double-masked, comparative study in which 40 and 45 subjects were randomized to groups receiving BID dosing and QD dosing, respectively. Subjects self-instilled the study drug for 14 days postoperative and were followed for an additional 2-week evaluation phase. The primary efficacy endpoint was the proportion of subjects with an anterior chamber cell (ACC) grade of 0 at day 15.ResultsA total of 45 subjects had cleared ACC (grade “0”) at day 15, of whom 21 were in the BID group (52.5%) and 24 were in the QD group (53.5%). A secondary analysis found 7/40 (17.5%) subjects in the BID group and 10/45 (22.2%) subjects in the QD group achieved an ACC grade of 0 at day 8. There were more adverse events in the QD group (n = 16) than in the BID group (n = 12).ConclusionSimilar outcomes were observed for subjects using Bromfenac 0.075% in DuraSite® in the BID and QD dosing regimens for the treatment of post-cataract surgery inflammation.Trial registrationClinicalTrials.gov identifier, NCT01190878.FundingInSite Vision (now a division of Sun Pharma).

Comparative evaluation of once-daily and twice-daily dosing of topical bromfenac 0.09%: aqueous pharmacokinetics and clinical efficacy study

“…Our findings largely corroborated with previous studies evaluating the clinical efficacy of topical NSAIDs. 13,16,25 The AC flare measured by flaremeter was significantly higher in the control group than the patients who received bromfenac over 3 months of follow-up, with both once-daily and twice-daily bromfenac groups having comparable outcomes. Endo et al reported a decrease in AC flare to the preoperative level by 2 weeks in the bromfenac group but persistently elevated levels through 6 weeks in the steroid group.…”

Roles of biomaterials in modulating the innate immune response in ocular therapy

“…On the other hand, PLGA (Casey et al, 2019;Ganugula et al, 2020;Luo et al, 2020), PLA (Sakai et al, 2006;Sakai et al, 2011), poly-caprolactone (PCL) (Yenice et al, 2008;du Toit et al, 2013), polyacrylic acid (PAA) (Trattler and Hosseini, 2017), and poly (amidoamine) (PAMAM) (Iezzi et al, 2012;Yavuz et al, 2016) are the most commonly used synthetic biomaterials as carriers of anti-inflammatory medications in ophthalmic therapy. According to Casey et al (2019), PLGA and PLA particles have broad-acting mechanisms that inhibit TLR signaling by programming innate immune cells, and they exhibit inherent immunomodulatory properties depending on their physiochemical properties.…”

“…The most common immunosuppressive agents are steroids. They have been used in a large number of commercial antiinflammatory ocular drugs such as Bromfenac and INVELTYS ™ , both of which contain cross-linked PAA or chitosan polymer; they are widely used for treating post-ocular surgery inflammation, reducing post-surgery pain, and DED (Bowman et al, 2009;Schopf et al, 2015;Trattler and Hosseini, 2017;Kim et al, 2018;Gupta and Venkateswaran, 2021). Steroidal immunosuppressants have several drawbacks; they require high administration dosages, frequent injections in chronic ocular inflammatory diseases that lead to defects in the innate immune system, and other long-term side effects such as cataracts and IOP in the eye.…”