Study of the Pharmacodynamic Activity of P-321 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease

Study Overview
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Brief Summary
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The purpose of this Phase 2a study is to assess changes in tear volume by the non-invasive techniques Ultra High Resolution Optical Coherence Tomography (UHR-OCT) following the administration of P-321 Ophthalmic Solution or Placebo in subjects with tear deficient dry eye disease.

Detailed Description
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This is a single-center, randomized, cross-over placebo controlled study to evaluate the changes in tear volume by P-321 Ophthalmic Solution and Placebo. The study will enroll subjects with tear deficient dry eye disease to receive sequentially one of two treatment sequences: P-321 Ophthalmic Solution then Placebo or Placebo then P-321. The study will consist of two Phases: In each Phase, subjects will be treated with P-321 Ophthalmic Solution under the same study design. Approximately twenty-four eligible subjects will complete the study with approximately 8 subjects participating in Phase 1 and the remainder of the 24 subjects participating in the phase 2. Decisions on the dose to be used in Phase 2 will be made based on Phase 1 data. The study will consist of three study visits: a Screening Visit (Visit 1), and two treatment visits (Visit 2 and Visit 3). The primary and secondary outcome measures will be assessed at each treatment visit. Safety assessments include adverse events (AEs).

Official Title
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Randomized, Crossover Study of the Pharmacodynamic Activity of P-321 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease Characterized by Low Tear Volume

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Drug: P-321 Ophthalmic Solution
* Drug: P-321 Ophthalmic Solution placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Male or female subjects aged 18 to 80 years Have a history of predominantly tear-deficient dry eye of mild to moderate severity, supported by a previous clinical diagnosis Have normal lid anatomy Subjects must: Remain on current medications for the duration of the study and have been on the current medication regimen at least during the past 28 days Exclusion Criteria: Have undergone refractive eye surgery in either eye during the past 12 months Have undergone uncomplicated cataract surgery in either eye during the past 3 months Have undergone previous eyelid surgery in either eye (External blepharoplasty, not resulting in exposure or abnormal blinking is allowed) Have undergone botulinum toxin (BotoxTh1 or equivalent) injection in the periocular area within 3 months prior to Visit 1 Subjects that have a systemic, multi-organ disease requiring active medical or surgical treatment are excluded with the exception of subjects with SS or GVHD Have punctal plugs, punctal occlusion, history of nasolacrimal duct obstruction or wear scleral lens. Past or present exposure keratopathy, neurotrophic keratopathy, lagophthalmos, or trichiasis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P-321 Ophthalmic Solution<br>0.017% P-321 Ophthalmic Solution will be administered to approximately 8 patients in Phase I and either 0.05% P-321 Ophthalmic Solution or 0.01% P-321 Ophthalmic Solution or additional 0.017% P-321 Ophthalmic Solution will be administered to approximately 16 patients in Phase II | Drug: P-321 Ophthalmic Solution<br> <br> * Other names: P-321;|
| Placebo Comparator: Drug: P-321 Ophthalmic Solution placebo<br>Placebo treatment administered to approximately 8 patients in Phase I and approximately 16 patients in Phase II | Drug: P-321 Ophthalmic Solution placebo<br> <br> * Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Tear Meniscus Volume Following the Administration of P-321 Ophthalmic Solution or Placebo | Tear meniscus volume, from measurements of tear meniscus area by UHR-OCT and the length of the eyelid was estimated over time (0 to 6 hours) following administration of placebo or P-321 Ophthalmic Solution. | Pre-dose and up to six hours after dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower Tear Meniscus Height as Measured by the Keratograph 5M | Tear meniscus height of the inferior eyelid was measured with the Keratograph 5M over time (0 to 6 hours) following the administration of placebo or P-321 Ophthalmic Solution | Pre-dose and up to six hours after dose | 
| Comparison of Lower Tear Meniscus Height Measurements Between UHR-OCT and Keratograph 5M | Tear meniscus height of the inferior eyelid was measured by UHR-OCT and Keratograph 5M over time (0 to 6 hours) following the administration of placebo or P-321 Ophthalmic Solution | Pre-dose and up to six hours after dose | 
| Adverse Events | Number of patients experiencing adverse events comparing P-321 to placebo | 2 or 7 hours |