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

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

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.

Study Overview

• Status: Terminated
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: P-321 Ophthalmic Solution; Drug: P-321 Ophthalmic Solution placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Plantation, Florida, United States, 33324
      • Bascom Palmer Eye Institute, University of Miami Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide written informed consent
2. Male or female subjects aged 18 to 80 years
3. Have a history of predominantly tear-deficient dry eye of mild to moderate severity, supported by a previous clinical diagnosis
4. Have normal lid anatomy

5. Subjects must:

   1. 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:

1. Have undergone refractive eye surgery in either eye during the past 12 months
2. Have undergone uncomplicated cataract surgery in either eye during the past 3 months
3. Have undergone previous eyelid surgery in either eye (External blepharoplasty, not resulting in exposure or abnormal blinking is allowed)
4. Have undergone botulinum toxin (BotoxTh1 or equivalent) injection in the periocular area within 3 months prior to Visit 1
5. 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
6. Have punctal plugs, punctal occlusion, history of nasolacrimal duct obstruction or wear scleral lens.
7. Past or present exposure keratopathy, neurotrophic keratopathy, lagophthalmos, or trichiasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: P-321 Ophthalmic Solution; 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; Other Names: P-321
Placebo Comparator: Drug: P-321 Ophthalmic Solution placebo; Placebo treatment administered to approximately 8 patients in Phase I and approximately 16 patients in Phase II	Drug: P-321 Ophthalmic Solution placebo; Other Names: Placebo; Placebo Comparator

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Parion Sciences
• Investigators: Study Director: Jose Boyer, Parion Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: July 1, 2016
• First Submitted That Met QC Criteria: July 1, 2016
• First Posted (Estimate): July 7, 2016

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 3, 2018
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Ophthalmic Solutions; Pharmaceutical Solutions
• Other Study ID Numbers: P-321-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No