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:

1. Provide written informed consent.

2. Are 18 - 80 years of age.

3. Corneal fluorescein staining score ≥2/15 on the NEI/Industry scale

4. Conjunctival lissamine staining score of ≥ 2/18 on the NEI/Industry scale

5. Schirmer <10mm/5min

6. Are willing and able to follow instructions and can be present for the required
study visits for the duration of the study.

7. 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.

8. 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.

9. Have documented history of topical lubricants at least daily or the desire to
use topical lubricants in the past 4 months.

10. Have normal lid anatomy

Exclusion Criteria:

- Individuals are not eligible for study participation if:

1. Have anterior segment eye disease except primary dry eye.

2. 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.

3. Patients with current punctal plugs, punctal occlusion, or history of
nasolacrimal duct obstruction are excluded.

4. 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

5. Contact lenses wear in the previous 30 days or during the Treatment Phase of the
study.

6. Use of lid scrubs (including baby shampoos)

7. 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.

8. Any significant chronic illness that, in the opinion of the Principal
Investigator (PI), could interfere with the study parameters.

9. Use of any investigational product or device within 30 days prior to the
Screening Visit or during the study.

10. Those unable in the opinion of the PI to comply fully with the study
requirements or complete the study.