Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: results of a randomized clinical trial

Michael A Patane, Amy Cohen, Stephen From, Gail Torkildsen, Donna Welch, George W Ousler 3rd, Michael A Patane, Amy Cohen, Stephen From, Gail Torkildsen, Donna Welch, George W Ousler 3rd

Abstract

Purpose: To assess safety and efficacy of EGP-437 (dexamethasone phosphate 40 mg/mL [DP]) in dry eye patients.

Methods: The study employed a prospective, single-center, double-masked design utilizing a Controlled Adverse Environment (CAE). Patients (n = 103) with confirmed signs and symptoms of dry eye syndrome were randomized into 1 of 3 iontophoresis treatment groups: 7.5 mA-min at 2.5 mA (DP 7.5, n = 41); 10.5 mA-min at 3.5 mA (DP 10.5, n = 37); or 10.5 mA-min at 3.5 mA (placebo, n = 25). Three CAE visits and 4 follow-up visits occurred over 3 weeks. Patients meeting enrollment criteria received iontophoresis in both eyes after the second CAE exposure (visit 3) and before the third CAE exposure (visit 5). Primary efficacy endpoints were corneal staining and ocular discomfort. Secondary endpoints included tear film break-up time, ocular protection index (OPI), and symptomatology.

Results: The DP 7.5 and DP 10.5 treatment groups showed statistically significant improvements in signs and symptoms of dry eye at various time points; however, the primary endpoints were not achieved. The DP 7.5 treatment group exhibited statistically significant improvements in corneal staining (when comparing the differences between study entry and exit, 3 weeks, P = 0.039), OPI (immediately following the second treatment, P = 0.048) and ocular discomfort at follow-up visits (a week after the first treatment, P = 0.032; 24 hours after the second treatment, P = 0.0032). Treatment-emergent adverse events (AEs) were experienced by 87% of patients and were consistent across all treatment groups. Most AEs were mild and no severe AEs were observed.

Conclusion: Ocular iontophoresis of EGP-437 demonstrated statistically and clinically significant improvements in signs and symptoms of dry eye syndrome within a CAE model.

Keywords: Controlled Adverse Environment (CAE); dry eye; iontophoresis; ocular protection index (OPI).

Figures

Figure 1
Figure 1
Study visit schedule. Diagram represents the overall study timeline, delineating the temporal relationship between screening visits, Controlled Adverse Environment (CAE) and drug dosing sessions, and the recovery period.
Figure 2
Figure 2
Ocular iontophoresis application. The photo shows the iontophoretic applicator placement on the eye.
Figure 3
Figure 3
Patient disposition. The flow chart depicts the distribution of patients throughout the study as well as inclusion/exclusion numbers, study populations, and treatment arms. Abbreviations: DP, dexamethasone phosphate; ITT, intention to treat; PP, per protocol.
Figure 4
Figure 4
Corneal staining is decreased by iontophoretic dexamethasone phosphate. The mean change in corneal fluorescein staining (inferior region) between visit 1 (baseline) to visit 7 for each treatment group. Over this time frame, the DP 7.5 treatment group showed a statistically significant decrease in staining compared with the placebo treatment group. Abbreviation: DP, dexamethasone phosphate.
Figure 5
Figure 5
Mean ocular discomfort scores during CAE exposure at visit 5. The plot depicts the mean discomfort scores for the placebo and DP 7.5 treatment groups during the course of the visit 5 CAE session. The DP 10.5 group, which was not significantly different from placebo, is omitted for clarity. Data included in the mean value calculation were from the PP-WE population of each group. The DP 7.5 group mean values are significantly lower (P < 0.05) than placebo for all times >60 minutes. Error bars represent standard error of the mean. Abbreviations: CAE, Controlled Adverse Environment; DP, dexamethasone phosphate; PP-WE, per protocol-worst eye.

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