RESUMO
PURPOSE: KPI-121 is a nanoparticle suspension of loteprednol etabonate with improved ocular pharmacokinetics compared with marketed formulations. The efficacy and safety of KPI-121 1% ophthalmic suspension (INVELTYS™) dosed twice daily (BID) were evaluated in participants who had undergone cataract surgery. MATERIALS AND METHODS: In two multicenter, randomized, double-masked, parallel-group, vehicle-controlled clinical trials, 386 participants with ≥ grade 2 anterior chamber cells (≥6 cells) on the day following routine cataract surgery were treated with KPI-121 1% and 325 participants were treated with placebo (vehicle); each group was dosed BID for 2 weeks. Primary efficacy endpoints were complete resolution of ocular inflammation by slit-lamp biomicroscopy and complete resolution of subject-rated ocular pain at Days 8 and 15 with no rescue medication before Day 15. Safety assessments included adverse events (AEs), visual acuity, intraocular pressure measurements, and evaluation of ocular AEs by slit-lamp biomicroscopy and dilated ophthalmoscopy. RESULTS: Both trials achieved statistical significance favoring KPI-121 1% BID for both primary efficacy endpoints. Combined data analysis showed that significantly more participants treated with KPI-121 vs vehicle achieved complete resolution of anterior chamber cells at Days 8 and 15 (P≤0.0001) and complete clearing of ocular pain at Days 4, 8, and 15 (P<0.0001). AEs were reported more frequently with vehicle than KPI-121. CONCLUSION: KPI-121 1% ophthalmic suspension was effective in resolving postoperative ocular inflammation and pain when dosed BID for 2 weeks in patients following cataract surgery. KPI-121 was found to be safe and well tolerated in both trials.
RESUMO
PURPOSE: To evaluate the safety, tolerability, and intraocular pressure (IOP)-lowering effect of Latrunculin-B (Lat-B), a marine macrolide that disrupts the actin cytoskeleton, in patients with ocular hypertension (OHT) or early primary open-angle glaucoma (POAG). METHODS: In this Phase I, multicenter, double-masked, randomized, placebo-controlled, ascending-dose study, subjects with bilateral OHT or early POAG (>22 mm Hg) received one of four concentrations of INS115644 (Lat-B ophthalmic solutions, 0.005%, 0.01%, 0.02%, or 0.05%) in one eye over 3 days (5 single-dose instillations, separated by 12 hours). One eye was randomly assigned to active drug, the other to placebo. IOP was measured prior to treatment initiation (day 0) and on days 1 and 3. RESULTS: Baseline IOPs were 22.9 ± 2.4 mm Hg and 23.5 + 3.1 mm Hg in the 0.02% and 0.05% dose groups, respectively. At 4 hours post instillation of the first dose, 0.02% INS115644 reduced IOP from baseline (mean ± SE) by 3.8 ± 0.7 mm Hg (P = 0.002) and 0.05% by 3.9 ± 1.0 mm Hg (P = 0.004). A maximum IOP decrease of 24% was noted at 4 hours after the fifth instillation of 0.02%. Adjusting for diurnal baseline and IOP in the contralateral, placebo-treated eye, the maximal 12-hour hypotensive effect was 4.0 ± 0.5 mm Hg (adjusted mean ± SE), a 17% decrease, following the fifth instillation of 0.02% (day 3). Adverse events were few and consisted mainly of mild redness, irritation, and a transient, clinically insignificant increase (≤2.5%) in central corneal thickness. CONCLUSIONS: In OHT or POAG patients, twice daily Lat-B significantly lowered IOP compared with contralateral, placebo-treated eyes, with few and mild ocular adverse events. TRANSLATIONAL RELEVANCE: Lat-B may be a potential therapeutic agent for glaucoma.
