Study to Assess the Efficacy, Safety and Tolerability of AKB-9778 Ophthalmic Solution as and Adjunct to Latanoprost in Patients With Ocular Hypertension or Open Angle Glaucoma

Study Overview
=================
Brief Summary
-----------------
This is a phase 2, double masked, randomized, multi-center, parallel-group, 28-day study assessing the safety, tolerability and ocular hypotensive efficacy of AKB-9778 Ophthalmic Solution 4.0% administered once (AM) or twice (AM & PM) daily when used as an adjunctive therapy to latanoprost ophthalmic solution 0.005% once daily (PM) in subjects with elevated IOP due to OAG or OHT.

Official Title
-----------------
Phase 2 Multi-Center, Double-Masked, Randomized, 28-Day Study to Assess the Efficacy, Safety and Tolerability of Single or Twice Daily Doses of AKB-9778 Ophthalmic Solution as an Adjunct to Latanoprost in Patients With Ocular Hypertension (OHT) or Open Angle Glaucoma (OAG)

Conditions
-----------------
Ocular Hypertension, Primary Open Angle Glaucoma

Intervention / Treatment
-----------------
* Drug: Latanoprost ophthalmic solution
* Drug: AKB-9778 4%
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Diagnosis of OAG or OHT in each eye (OAG in one eye and OHT in the fellow eye is acceptable) Must be receiving treatment with a stable regimen of topical prostaglandin eyedrop for a minimum of 2 weeks prior to the Screening Visit; may be taking one additional IOP lowering eyedrop IOP of ≥ 18 mmHg and ≤ 27 mmHg in one eye or both eyes at Screening visit Following 4 week washout period, IOP ≥ 24 mmHg and < 36 mmHg at 08:00 hour and IOP ≥ 22 mmHg and < 36 mmHg in both eyes at 10:00, 12:00 and 16:00 hours. Key Exclusion Criteria: Clinically significant ocular disease which might interfere with interpretation of the study efficacy endpoints or with safety assessments Pseudoexfoliation or pigment dispersion component glaucoma History of angle closure glaucoma, or narrow angles or with evidence of peripheral anterior synechiae (PAS) ≥ 180 degrees by gonioscopy within 6 months prior to Screening Intraocular pressure ≥ 36 mmHg Cup/disc ratio of > 0.8 in either eye Severe visual field defect or significant defect (sensitivity of ≤ 10dB) within 10 degrees of fixation in either eye

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKB-9778 4% QD + Latanoprost<br>• AKB-9778 4% daily (AM) and placebo for ophthalmic solution daily (PM) plus latanoprost daily (PM) for 28 days | Drug: Latanoprost ophthalmic solution<br>* Latanoprost opthalmic solution to be dosed once daily<br>Drug: AKB-9778 4%<br>* Razuprotafib opthalmic solution<br>|
| Experimental: AKB-9778 4% BID + Latanoprost<br>• AKB-9778 4% twice daily (AM & PM) plus latanoprost daily (PM) for 28 days | Drug: Latanoprost ophthalmic solution<br>* Latanoprost opthalmic solution to be dosed once daily<br>Drug: AKB-9778 4%<br>* Razuprotafib opthalmic solution<br>|
| Placebo Comparator: Placebo Twice Daily + Latanoprost<br>• Placebo for AKB-9778 4% ophthalmic solution twice daily (AM & PM) plus latanoprost daily (PM) for 28 days | Drug: Latanoprost ophthalmic solution<br>* Latanoprost opthalmic solution to be dosed once daily<br>Drug: Placebo<br>* placebo for razuprotafib opthalmic solution<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Intraocular Pressure at Day 28 (Study Eye) | Change from Baseline in Diurnal Mean IOP (mmHg) at Day 28 in the Study Eye -- ITT Population | Baseline to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Diurnal Mean IOP at the Day 14 Visit (Study Eye) | Change from Baseline in Diurnal Mean IOP (mmHg) at Day 14 in the Study Eye -- ITT Population | Baseline to Day 14 | 
| Mean Change From Baseline in Diurnal Mean IOP on Days 14 and 28 (Both Eyes) | Mean change from baseline in diurnal mean IOP (measured in mmHg) at Day 14 and 28 in both eyes - ITT Population | Baseline to Day 14 and Baseline to Day 28 | 
| Observed Mean Diurnal Mean IOP on Days 14 and 28 (Both Eyes) | Mean of the Diurnal Mean IOP (mmHg) at Day 14 and Day 28 in both eyes -- ITT Population | Baseline to Day 14 and Baseline to Day 28 | 
| Mean Observed IOP at Each Time Point on Days 14 and 28 | Mean observed IOP measured in mmHg at each time point on Days 14 and 28 (study eye) - ITT Population | Baseline to each timepoint on Day 14 and Baseline to each timepoint on Day 28 | 
| Mean Change From Baseline IOP at Each Time Point on Days 14 and 28 | Change from Baseline in Mean IOP (mmHg) at Each Time Point on Day 14 and Day 28 in the Study Eyes -- ITT Population | Baseline to each timepoint on Day 14 and Baseline to each timepoint on Day 28 | 
| Mean Percent Change From Diurnally Adjusted Baseline IOP at Each Time Point on Days 14 and 28 | Percent Change from Baseline IOP (mmHg) at Each Time Point on Day 14 and Day 28 in the Study Eyes -- ITT Population | Baseline to each timepoint on Day 14 and Baseline to each timepoint on Day 28 | 
| Mean Percent Change From Baseline in Diurnal Mean IOP on Days 14 and 28 | Percent Change from Baseline in Diurnal Mean IOP (mmHg) at Day 14 and Day 28 in the Study Eye -- ITT Population | Baseline to Day 14 and Baseline to Day 28 | 
| Percentages of Subjects Achieving Pre-Specified Mean, Mean Change, and Percent Mean Change in Diurnal Mean IOP Levels | Percentages of Subjects Achieving Pre-Specified Mean, Mean Change, and Percent Mean Change in Diurnal Mean IOP Levels in Study Eye -- ITT Population | Baseline to Day 28 |