Efficacy and Safety of APP13007 for Treatment of Inflammation and Pain After Cataract Surgery Including a Corneal Endothelial Cell Sub-study

Study Overview
=================
Brief Summary
-----------------
This Phase 3 study will evaluate APP13007 in comparison to the matching vehicle placebo in a randomized, parallel-group, double-masked fashion. The subjects will have undergone routine cataract surgery on Day 0 of the study and will be assessed the next day (Post-operative Day; POD1) after uncomplicated surgery for eligibility for randomization to study treatment. The study comprises the Main Study and the Endothelial Cell Sub-study.

Official Title
-----------------
A Multicenter, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of APP13007 for the Treatment of Inflammation and Pain After Cataract Surgery, Including a Corneal Endothelial Cell Sub-study

Conditions
-----------------
Ocular Inflammation and Pain After Cataract Surgery

Intervention / Treatment
-----------------
* Drug: APP13007, 0.05%
* Drug: Matching Vehicle Placebo for APP13007, 0.05%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients 18 years of age or older expected to undergo unilateral uncomplicated cataract extraction via phacoemulsification and posterior chamber intraocular lens implantation in one eye. Have a pin-hole corrected visual acuity without other correction of ≤ 1.3 logarithm of the minimum angle of resolution (logMAR) in the study eye to be operated and contralateral eye as measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart at Visit 1. Willing and able to comply with study requirements and visit schedule. Provide signed and dated informed consent. Exclusion Criteria: Have a known sensitivity or allergy to clobetasol propionate, corticosteroids, or any of the study medication's components including benzalkonium chloride and soybean lecithin or any routine medication required during cataract surgery or for the conduct of study procedures Have an ACC count > 0 or any evidence of intraocular inflammation (e.g., flare) in either eye at the Screening visit Have a Grade > 0 on the Ocular Pain Assessment in either eye at the Screening visit Note: Other inclusion/exclusion criteria apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APP13007 0.05% BID<br>1 drop APP13007 0.05% twice daily for 14 days to study (operated) eye | Drug: APP13007, 0.05%<br>* APP13007 eye drop, 0.05%<br>|
| Placebo Comparator: Matching Vehicle Placebo<br>1 drop matching vehicle placebo twice daily for 14 days to study (operated) eye | Drug: Matching Vehicle Placebo for APP13007, 0.05%<br>* Matching vehicle placebo eye drop<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With ACC Count = 0 in the Operated Study Eye at All Visits From Postoperative Day 8 Through Postoperative Day 15 Without Rescue Medication | The number of cells in the anterior chamber of the eye are counted using slit-lamp biomicroscopy at each study visit and the results are reported as number of cells in a 1mm x 1mm area. | Postoperative Day 8 and Postoperative Day 15 | 
| Participants With Ocular Pain Grade = 0 in the Operated Study Eye at All Visits From Postoperative Day 4 Through Postoperative Day 15 Without Rescue Medication | Ocular pain is measured in the eye using a subject-reported five-point (0-4) ocular pain grade scale (0 = no pain; 1 = minimal; 2 = mild; 3 = moderate; 4 = severe pain). | Postoperative Day 4, Postoperative Day 8 and Postoperative Day 15 | 
| Participants With Treatment-emergent Adverse Events (AEs) | Number of participants with ocular and systemic treatment-emergent AEs. | From First dose to Postoperative Day 22 (End of Main Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Anterior Chamber Cell Grade = 0 in the Operated Study Eye at POD8 Without Rescue Medication | The number of cells in the anterior chamber of the eye are counted using slit-lamp biomicroscopy at each study visit and the results are reported as number of cells in a 1mm x 1mm area.ACC Grade 0 = 0 cells, ACC grade 1 = 1-5 cells, ACC grade 2 = 6-15 cells, ACC grade 3 = 16-30 cells, ACC grade 4 = >30 cells. | Postoperative Day 8 | 
| Participants With Anterior Chamber Cell Grade = 0 in the Operated Study Eye at POD15 Without Rescue Medication | The number of cells in the anterior chamber of the eye are counted using slit-lamp biomicroscopy at each study visit and the results are reported as number of cells in a 1mm x 1mm area. ACC Grade 0 = 0 cells, ACC grade 1 = 1-5 cells, ACC grade 2 = 6-15 cells, ACC grade 3 = 16-30 cells, ACC grade 4 = >30 cells. | Postoperative Day 15 | 
| Participants With Ocular Pain Grade = 0 in the Operated Study Eye at POD4 Without Rescue Medication | Ocular pain is measured in the eye using a subject-reported five-point (0-4) ocular pain grade scale (0 = no pain; 4 = severe pain). | Postoperative Day 4 | 
| Participants With Ocular Pain Grade = 0 in the Operated Study Eye at POD8 Without Rescue Medication | Ocular pain is measured in the eye using a subject-reported five-point (0-4) ocular pain grade scale (0 = no pain; 4 = severe pain). | Postoperative Day 8 | 
| Participants With Ocular Pain Grade = 0 in the Operated Study Eye at POD15 Without Rescue Medication | Ocular pain is measured in the eye using a subject-reported five-point (0-4) ocular pain grade scale (0 = no pain; 4 = severe pain). | Postoperative Day 15 | 
| Participants With Anterior Chamber Flare (ACF) = 0 in the Operated Study Eye at POD4 Without Rescue Medication | The degree of turbidity (flare) in the anterior chamber of the eye is measured using slit-lamp biomicroscopy and quantified on a five-point (0-4) anterior chamber flare grade scale (0 = none; 4 = Intense). | Postoperative Day 4 | 
| Participants With Anterior Chamber Flare (ACF) = 0 in the Operated Study Eye at POD8 Without Rescue Medication | The degree of turbidity (flare) in the anterior chamber of the eye is measured using slit-lamp biomicroscopy and quantified on a five-point (0-4) anterior chamber flare grade scale (0 = none; 4 = Intense). | Postoperative Day 8 | 
| Participants With Anterior Chamber Flare (ACF) = 0 in the Operated Study Eye at POD15 Without Rescue Medication | The degree of turbidity (flare) in the anterior chamber of the eye is measured using slit-lamp biomicroscopy and quantified on a five-point (0-4) anterior chamber flare grade scale (0 = none; 4 = Intense). | Postoperative Day 15 | 
| Anterior Chamber Cell Grade in the Operated Study Eye - Change From Baseline (POD1 Prior to Dosing) to POD 15 | The number of cells in the anterior chamber of the eye are counted using slit-lamp biomicroscopy and the results are reported as number of cells in a 1mm x 1mm area using a 5 point grading scale. ACC Grade 0 = 0 cells, ACC grade 1 = 1-5 cells, ACC grade 2 = 6-15 cells, ACC grade 3 = 16-30 cells, ACC grade 4 = >30 cells | Baseline and Postoperative Day 15 | 
| Ocular Pain Grade in the Operated Study Eye - Change From Baseline (POD1 Prior to Dosing) to POD 15 | Ocular pain is measured in the eye using a subject-reported five-point (0-4) ocular pain grade scale (0 = no pain; 1 = minimal; 2 = mild; 3 = moderate; 4 = severe pain). | Baseline and Postoperative Day 15 | 
| Anterior Chamber Flare (ACF) in the Operated Study Eye - Change From Baseline (POD1 Prior to Dosing) to POD 15 | The degree of turbidity (flare) in the anterior chamber of the eye is measured using slit-lamp biomicroscopy and quantified on a five-point (0-4) anterior chamber flare grade scale (0 = none; 1 = faint; 2 = moderate; 3 = marked; 4 = Intense). | Baseline and Postoperative Day 15 | 
| Best Corrected Visual Acuity in the Operated Study Eye - Change From Baseline (POD1 Prior to Dosing) to POD4 | The visual acuity in each eye is corrected using the pinhole method and the acuity is quantified on a logMAR (minimal angle of resolution) scale using the 'Early Treatment Diabetic Retinopathy Study' [ETDRS] charts for right and left eyes. A logMAR Score is calculated using the letter row on the chart and the number of incorrect letters read by the participant. | Baseline and Postoperative Day 4 | 
| Best Corrected Visual Acuity in the Operated Study Eye - Change From Baseline (POD1 Prior to Dosing) to POD8 | The visual acuity in each eye is corrected using the pinhole method and the acuity is quantified on a logMAR (minimal angle of resolution) scale using the 'Early Treatment Diabetic Retinopathy Study' [ETDRS] charts for right and left eyes. A logMAR Score is calculated using the letter row on the chart and the number of incorrect letters read by the participant. | Baseline and Postoperative Day 8 | 
| Best Corrected Visual Acuity in the Operated Study Eye - Change From Baseline (POD1 Prior to Dosing) to POD15 | The visual acuity in each eye is corrected using the pinhole method and the acuity is quantified on a logMAR (minimal angle of resolution) scale using the 'Early Treatment Diabetic Retinopathy Study' [ETDRS] charts for right and left eyes. A logMAR Score is calculated using the letter row on the chart and the number of incorrect letters read by the participant. | Baseline and Postoperative Day 15 | 
| Participants Using of Anti-inflammatory 'Rescue' Medication Through End-of-Treatment | Participants who do not respond to study treatment after randomization are started on anti-inflammatory medication (referred to as 'Rescue' medication). The number of subjects starting 'Rescue' medication is recorded at each study visit | First dose to Postoperative Day 15 |