Study of the Safety and Tolerability of P 321 Ophthalmic Solution in Subjects With Dry Eye Disease

This is a single-center, dose escalation, randomized, double-masked, placebo-controlled, Phase 1/2a trial designed to evaluate the safety and tolerability of P-321 Ophthalmic Solution in subjects with mild to moderate dry eye for up to 4-weeks of treatment and up to 8 scheduled in clinic visits. This study will conduct a consecutive dose escalation of the following concentrations of P-321 Ophthalmic Solution given two times a day via ocular instillation: 0.0005% (Cohort 1), 0.0015% (Cohort 2), 0.005% (Cohort 3), and 0.01% (Cohort 4). Up to 48 subjects will be enrolled in four consecutive cohorts. Subjects will be randomized to P-321 Ophthalmic Solution or placebo in a 3:1 ratio.

Safety and tolerability assessments, drug plasma concentrations and drug urine concentrations will be evaluated throughout the study in all cohorts.

Inclusion criteria

• Individuals of both genders and any race will be eligible for study participation if they:

• Provide written informed consent.
• Are 18 - 80 years of age.
• Corneal fluorescein staining score ≥2/15 on the NEI/Industry scale
• Conjunctival lissamine staining score of ≥ 2/18 on the NEI/Industry scale
• Schirmer <10mm/5min
• Are willing and able to follow instructions and can be present for the required study visits for the duration of the study.
• Female patients of child bearing potential must have a negative urine pregnancy test at Screening and agree to use a medically acceptable form of birth control. Male subjects who are sexually active must be willing to use highly effective contraception (i.e., less than 1% failure rate) during heterosexual intercourse from Day 1 through completion of the study.
• Have a history of Dry Eye Disease in both eyes supported by a previous clinical diagnosis or have a self-reported history of subjective complaints for at least 4 months prior to Screening, low tear volume, and ocular staining.
• Have documented history of topical lubricants at least daily or the desire to use topical lubricants in the past 4 months.
• Have normal lid anatomy

Exclusion criteria

• Individuals are not eligible for study participation if:

• Have anterior segment eye disease except primary dry eye.
• Patients with an identifiable or suspected secondary dry eye, i.e., a documented or likely systemic, ocular, pharmacologic, post-traumatic, post-surgical, or external cause for dry eye symptoms or ocular surface staining.
• Patients with current punctal plugs, punctal occlusion, or history of nasolacrimal duct obstruction are excluded.
• Have a history of glaucoma or intraocular pressure (IOP) > 25 mmHg at the Screening Visit (Visit 1) or a history of elevated IOP within the past year prior to Visit 1
• Contact lenses wear in the previous 30 days or during the Treatment Phase of the study.
• Use of lid scrubs (including baby shampoos)
• Known hypersensitivity to the study investigational medicinal product, or formulation excipients, including amiloride or related drugs or allergies to the components of the study drug.
• Any significant chronic illness that, in the opinion of the Principal Investigator (PI), could interfere with the study parameters.
• Use of any investigational product or device within 30 days prior to the Screening Visit or during the study.
• Those unable in the opinion of the PI to comply fully with the study requirements or complete the study.