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To assess safety and ocular hypotensive efficacy of VVN539 ophthalmic solution in a first-in-human study. Multicenter, double-masked, randomized, vehicle-controlled, dose-response, parallel-comparison study. Sixty-eight subjects with ocular hypertension (OHT) or open-angle glaucoma enrolled at 5 private practices. After washout of ocular hypotensive medications as required, the subjects were randomized to receive either VVN539 ophthalmic solution 0.02%, 0.04%, or vehicle once-daily (QD) in the morning (5 days), once-daily in the evening (6 days) and then twice-daily (6 days). Comparison of VVNM539 to its vehicle in mean intraocular pressure (IOP) at each diurnal time point (8:00am, 10:00am, and 4:00pm) at visit 4 (day 7), visit 5 (day 14), and visit 6 (day 21). Mean IOP decreased throughout dosing in the active groups to between 18 and 20 mmHg in both active groups, to between 22 to 23 mmHg in the vehicle group. VVN539 0.04% was statistically superior to vehicle at all 9 diurnal time points (QD AM, QD PM, and twice daily, P ≤ 0.0109). VVN539 0.02% was statistically superior to vehicle at only 6 of 9 diurnal time points (selected QD times and twice daily). The most common ocular treatment-emergent adverse event was conjunctival hyperemia (11 [47.8%], 10 [4.5%], and 1 [4.3%]), followed by ocular hyperemia (3 [13.0%], 5 [22.7%] and 0), respectively. There were no clinically significant changes of note in visual acuity, biomicroscopy, dilated ophthalmoscopy, blood chemistry, hematology, or cardiovascular measures. In conclusion, the results of this initial phase II study indicate that VVN539 ophthalmic solution showed clinically and statistically significant ocular hypertensive activity and was relatively well tolerated for the treatment of subjects with primary open-angle glaucoma or OHT. Additional studies will be required for a more complete evaluation of the utility of VVN539 ophthalmic solution. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PurposeEvaluate the initial ocular safety and tolerability and efficacy of VVN001 Ophthalmic Solution (VVN001), a small-molecule antagonist of lymphocyte function-associated antigen-1 (LFA-1), in subjects with dry eye disease (DED).MethodsThis was a multi-center, double-masked, randomized, dose-response, vehicle-controlled, parallel-group study conducted in 170 subjects with DED. Subjects were randomized to receive VVN001 (1% or 5%) or its vehicle, twice-daily in both eyes for 84 days. The primary outcome measure was inferior region corneal fluorescein staining (iCFS, 0-4 scale) at Day 84. Visual Analogue Scale eye dryness (VAS, 0-100 scale) was a secondary outcome.ResultsThe primary and first secondary outcomes were not met. At Day 84 treatment effects in favor of VVN001 5% relative to its vehicle for iCFS were 0.29 units (p = 0.054), and for VAS were 3.18 units (p = 0.533). In other secondary outcomes, treatment effects in favor of VVN001 5% relative to its vehicle were seen in total CFS (1.61 units, 0-20 scale, p = 0.004) and Schirmer score (1.77 and 2.32 mm, p = 0.049 and p = 0.17 at Days 14 and 28 respectively). Adverse events of incidence 5% or greater in either active treatment group were instillation site pain (3/57, 5.3%), dysgeusia (3/56, 5.4%) and urinary tract infection (3/57, 5.3%).ConclusionsThere were no major safety issues of note. Appropriately powered studies will be required with a priori selection of the efficacy endpoints to evaluate VVN001's therapeutic potential.

PurposeTo perform a phase Ⅰ/Ⅱ evaluation of an H-1337 ophthalmic solution in subjects with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).DesignThis was a phase I/II, randomized, double-masked, vehicle-controlled, dose-response study conducted at 6 private practice sites in the United States. The study was registered with clinicaltrials.gov as NCT03452033.ParticipantsEighty-seven subjects with bilateral POAG or OHT were enrolled.MethodsAfter washout of ocular hypotensive medications as required, the subjects were randomized to receive either the H-1337 ophthalmic solution at 0.06%, 0.2%, and 0.6% or its vehicle twice daily unilaterally in the study eye for the first 3 days and then twice daily in both eyes from day 4 to 28.Main outcome measuresThe primary efficacy end point was the mean change in intraocular pressure from baseline (day 0) for each group on day 28 at hour 4 compared with the vehicle.ResultsIn the primary efficacy end point, i.e., mean change from the baseline on day 28 at hour 4, the mean change from the baseline was - 4.45 ± 3.801, - 5.16 ± 3.114, - 4.93 ± 3.110, and - 0.39 ± 2.355 in the 0.06%, 0.2%, and 0.6% H-1337 and vehicle groups, respectively. The difference between each active group and the vehicle group was statistically significant (P < 0.0001). Treatment-emergent adverse events (TEAEs) occurred in 49% of subjects who received H-1337 (range, 41% [0.2% arm]-64% [0.6% arm] across the H-1337 arms) and 18% of subjects who received the vehicle. The majority of TEAEs were mild in severity; 3 subjects who received H-1337 had a TEAE of moderate intensity (instillation site erythema, blurred vision, and muscle strain).ConclusionsThe H-1337 ophthalmic solution showed clinically and statistically significant ocular hypotensive activity and was well tolerated, with a relatively low incidence of hyperemia.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Treatment of ocular diseases presents unique challenges and opportunities for the clinician and for the clinical pharmacologist. Ophthalmic pharmaceuticals, typically given as liquids, require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Ocular tissue levels are challenging to obtain in humans, and the clinical pharmacokinetics is typically blood levels, which are primarily related to safety, rather than efficacy. The eye is a closed compartment with multiple physiological barriers with esterases and transporters, but relatively little cytochrome oxidases. Delivery routes include topical, intravitreal, and systemic. Patient dosing involves not only adherence issues common to all chronic diseases, but also performance requirements on eye drop instillation. Therapeutically, ocular diseases and their pharmacological treatments include both those analogous to systemic diseases (e.g., inflammation, infection, and neuronal degeneration) and those unique to the eye (e.g., cataract and myopia). [ABSTRACT FROM AUTHOR]

Purpose: The safety and efficacy of a novel topical ocular anesthetic (AG-920 sterile ophthalmic solution, 8%) was previously evaluated in adults. For both clinical and regulatory purposes, this new agent was evaluated in children. Methods: This was a Phase 3, randomized, active-controlled, single-masked, parallel-group design study in healthy pediatric subjects performed at a private practice retina clinic in the United States. The safety and anesthetic efficacy of AG-920 was compared with proparacaine hydrochloride ophthalmic solution 0.5% in 60 children undergoing ophthalmic examinations. The primary efficacy endpoint was whether the investigator was able to perform the eye examination. Results: In all subjects in each treatment group, the investigator was able to perform the eye examination without additional local anesthetic. There were no adverse events reported in this study. In both the study eye and fellow eye, there were no notable changes after dosing, and both treatment groups were similar. All external eye exams in all subjects in both treatment groups were normal. Conclusions: In this pediatric population aged 7 months to >11 years, AG-920 was therapeutically equivalent to marketed proparacaine with respect to having an ophthalmic examination performed without needing additional local anesthetic. Further, AG-920 was well tolerated, and there were no clinically significant safety findings. [ABSTRACT FROM AUTHOR]