Reexamining Ophthalmic Drugs, Safety and Tolerability in Phase 1 Clinical Trials

Patricia Muñoz-Villegas, Andrea A Navarro-Sánchez, Alejandra Sánchez-Ríos, Oscar Olvera-Montaño, Leopoldo M Baiza-Durán, Patricia Muñoz-Villegas, Andrea A Navarro-Sánchez, Alejandra Sánchez-Ríos, Oscar Olvera-Montaño, Leopoldo M Baiza-Durán

Abstract

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.

Keywords: healthy volunteer; ophthalmic drug; phase 1 trial; safety; tolerability.

Conflict of interest statement

This study was sponsored by Laboratorios Sophia, S.A. de C.V. (Zapopan, Jalisco, Mexico). The funder provided support in the form of salaries for authors, but this commercial affiliation did not have any additional role in the data collection.

© 2021 Muñoz-Villegas et al.

Figures

Figure 1
Figure 1
Incidence of adverse events (AE) in 166 NHV for approved drugs (AD, upper polar graphs) and investigational drugs (ID, lower polar graphs). A total of 205 adverse events were presented in 59.6% NHV (99/166). For another AE the incidence was lubricant and antibiotic drugs, Chi square test, p = 0.0001.
Figure 2
Figure 2
Flow chart of studies.

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