Topical ENaC blocker serves as novel approach to tear film
First-in-human trial encouraging, identifies agent that is associated with signs of improvement in tear function
Durham, NC—A novel potent epithelial sodium channel (ENaC) blocker seems to be a safe and well-tolerated therapy in patients with symptoms of mild-to-moderate dry eye disease compared with placebo.
The rationale behind the development of this product, as explained by José L. Boyer, PhD, is that the ocular surface epithelia are important players in fluid regulation by the cornea and conjunctiva.
This type of regulation also occurs elsewhere in the body in the epithelia of the lung, gastrointestinal tract, and kidneys. The ocular surface epithelia regulate mucosal hydration through a coupled process involving Na+ absorption and Cl- secretion, he explained.
“The inhibition of ENaC on the ocular surface is predicted to block pathways for tear absorption and at the same time provide a driving force for water secretion, resulting in increased hydration of the ocular surface,” Dr. Boyer pointed out. He is vice president of Research and Ophthalmology Development, head of development of the P-321 dry eye program, Parion Sciences Inc., Durham, NC, and a lead author of the P-321-101 study.
The ENaC blocker under discussion, P-321 ophthalmic solution (Parion Sciences), was evaluated in a single-center, dose-escalation, randomized, double-masked, placebo-controlled, phase I/IIa trial to determine its safety and tolerability in patients with mild-to-moderate dry eye compared with placebo, said co-author Gary Foulks, MD, emeritus professor of ophthalmology, University of Louisville, Louisville, KY.
The study included four consecutive cohorts. Cohorts 1-3 evaluated the drug for up to 15 days and cohort 4 extended the evaluation out to 28 days. Four concentrations of P-321 were tested: 0.0005%, 0.0015%, 0.005%, and 0.01%, in the patients in cohorts 1-4, respectively. The participants instilled one drop of the drug or placebo in each eye twice daily.
The inclusion criteria included men and women aged 18 to 80 years of age with a documented history of dry eye symptoms for at least 4 months who needed to use a topical lubricant or who desired to use topical lubricants at least daily in the past 4 months.
The patients had a Symptom Assessment iN Dry Eye (SANDE) score exceeding 20 and less than 90 for severity and exceeding 10 and less than 90 for frequency, phenol red thread test below 10 millimeters per 15 seconds or a Schirmer’s test score of less than 10 millimeters per 5 minutes, a corneal fluorescein staining score of 2 (out of 15) or higher, or conjunctival staining score of 2 (out of 18) or higher. The use of artificial tears was prohibited during the study.
Subjects with mild-to-moderate dry eye disease who met the inclusion criteria were randomly assigned to either P-321 or placebo in a 3:1 ratio. Cohorts 1, 2, and 3 had five clinical visits with up to eight subjects enrolled in each cohort, and cohort 4 had eight visits and included 28 subjects.