ABSTRACT
PURPOSE: The safety of KPI-121 0.25%, an ophthalmic nanoparticle suspension of loteprednol etabonate, was evaluated in subjects with dry eye disease (DED) in one phase 2 and three phase 3 randomized trials of similar design. METHODS: Adults with DED received KPI-121 0.25% or vehicle drops 4 times daily (QID) for ≥2 weeks; 1430 subjects received KPI-121 0.25% and 1438 subjects received vehicle drops. Main safety assessments were adverse events (AEs) and intraocular pressure (IOP). As a common side effect associated with the use of ocular corticosteroids is elevated IOP, subjects with a history of or current diagnosis of glaucoma were excluded. RESULTS: Instillation site pain was the most common AE, reported by 5.2% of subjects in the KPI-121 0.25% group and 4.4% of subjects in the vehicle group; other AEs were reported by ≤0.8% of subjects in the KPI-121 group. IOP elevations, a side effect associated with the use of ophthalmic corticosteroids, were observed with low incidence: 0.6% and 0.2% of subjects in the KPI-121 and vehicle groups, respectively. An IOP elevation was defined as an increase from baseline of >5 mm Hg that resulted in an IOP of ≥21 mm Hg in either eye during use of the study product. CONCLUSIONS: KPI-121 ophthalmic suspension 0.25% seemed to be safe and well tolerated when dosed QID for 2 to 4 weeks in those DED subjects included in the 4 trials.
Subject(s)
Anti-Allergic Agents/administration & dosage , Dry Eye Syndromes/drug therapy , Loteprednol Etabonate/administration & dosage , Administration, Ophthalmic , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Allergic Agents/adverse effects , Double-Blind Method , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug-Related Side Effects and Adverse Reactions/etiology , Eye Pain/chemically induced , Female , Humans , Intraocular Pressure/drug effects , Loteprednol Etabonate/adverse effects , Male , Middle Aged , Nanoparticles , Ophthalmic Solutions , Suspensions , Tonometry, Ocular , Visual Acuity/drug effects , Young AdultABSTRACT
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.
