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Purpose: The goals of this study were to evaluate the safety and efficacy of an ophthalmic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based nanoemulsion (Nanodrop®) in patients with dry eye disease (DED). Methods: This was a randomized phase I/II multicentric, prospective, double-blind clinical trial. Patients (phase I: n = 25 and phase II: n = 101) were assigned to receive either PRO-176 (Nanodrop®) or Systane Balance® (control) for 29 days. Once the visits of the first 25 subjects were completed, if there were less than 20% of unexpected adverse events (AEs), related to PRO-176, recruitment was continued until the sample was completed for noninferiority (efficacy) analysis (phase II, n = 126). Efficacy endpoints were the ocular surface disease index (OSDI), tear break-up time (TBUT), epithelial defects, best corrected visual acuity (BCVA), and the incidence of expected AE. Results: For the phase I portion of the study, there were no differences between groups regarding the incidence of AE. All related-AE symptoms in both groups were mild and expected. For the phase II subset, there was a significant reduction in OSDI scores at day 29 and noninferiority between treatments was confirmed (p=0.650, CI 95% [-8.7, 5.5]). Similar improvement was observed for TBUT although no significant intergroup differences were found (p=0.518, CI 95% [-0.08, 1.6]). There were no significant differences between treatments for epithelial staining or safety parameters. Conclusions: Topical application of PRO-176 is as safe and effective as the controls. Both groups were clinically similar in terms of efficacy and safety. The results support the hypothesis that ophthalmic DMPC-based nanoemulsion may improve clinical parameters and symptoms in patients with DED. This trial is registered with NCT04111965.
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Purpose: To evaluate the rheological properties of the ophthalmic viscoelastic device (OVD) PRO-149, its preclinical safety, and its effectiveness when used during cataract surgery in patients with age-related cataract. Material and Methods: Control (HEC) and test (PRO-149) OVDs were compared through rheological measures, by two preclinical safety studies in rabbits, and under normal-use conditions during cataract removal and lens implantation in a parallel randomized clinical trial. Results: Rheological properties were determined. Preclinical studies did not find any evidence of safety issues or toxicity. In the clinical trial, 36 subjects were included. After 29 days, there were no statistically significant differences in mean percentage of endothelial cell count change or in the postoperative intraocular pressure between groups. There were no significant differences between OVDs for any safety parameter studied. Finally, PRO-149 showed a statistically significant improvement in surgeon rating for ease of use during extraction (p < 0.05). Conclusion: PRO-149 is a dispersive OVD. The rabbit models did not find evidence of clinical alterations or toxicity. The results of the clinical study support that the two studied OVDs were clinically similar in terms of safety and effectiveness for cataract surgery. Trial Registration: The trial is registered at Clinical Trials.gov at NCT04702802 (21-01-11).
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PURPOSE: The purpose of this study was to evaluate the safety and tolerability profile of drugs used for treating common eye disorders when applied to normal healthy volunteers (NHVs) as explored in phase 1 trials. SUBJECTS AND METHODS: A total of 166 NHVs were identified in six phase 1 trials, examined in a retrospective analysis. The primary endpoints were visual comfort (by ocular comfort index, OCI) and safety (laboratory evaluations, vital signs (VS), visual acuity (VA), intraocular pressure (IOP), lissamine green and fluorescein staining, conjunctival hyperemia, chemosis, and adverse events' incidence (AE)). RESULTS: Compared to baseline, 75.9%, 40.4% and 73.7% of NHV (for lubricant, hypotensive and antibiotic treatments, respectively) improved their OCI score by their final visit. Laboratory evaluations and VS were within normal ranges in 88% of NHV. Similar results were found for VA, corneal and conjunctival staining, and chemosis. IOP decreased significantly in the hypotensive agents' group, trace to mild hyperemia was reported in 32.1%, 27.1%, and 6.8%, respectively. Additionally, lubricant and hypotensive investigational drugs (ID) had a lower risk of incidence of AE than approved drugs (OR 0.856, 95% CI [0.365, 1.999] and 0.636, 95% CI [0.096, 4.197], respectively). Meanwhile, on antibiotic drugs, the risk for ID-related AE was higher (OR 1.313, 95% CI [0.309, 5.583]). CONCLUSION: Phase 1 trials are important in order to ensure the safety and tolerability of ophthalmic medications. This study demonstrates that NHVs do not face a significant risk of harm in these studies, since 98% of the reported AE were mild, and all AE were resolved by the end of the study in which they appeared. TRIAL REGISTRATION: This is a retrospective study of six previously conducted clinical trials, registered on clinicaltrials.gov with the following registration IDs: NCT04081610, NCT03524157, NCT03520348, NCT03966365, NCT03965052 and, NCT03519516.
