Study of Netarsudil Ophthalmic Solution in Subjects With Primary Open Angle Glaucoma (POAG) or Ocular Hypertension (OHT)

Study Overview
=================
Brief Summary
-----------------
To evaluate the effect on trabecular outflow facility of Netarsudil ophthalmic solution 0.02% compared to placebo

Detailed Description
-----------------
Trabecular outflow facility is a measure of aqueous humor dynamics; effect of netarsudil on this parameter as well as on intraocular pressure and episcleral venous pressure was evaluated in this study. Netarsudil treatment was given in one eye and placebo given in contralateral eye for 7 consecutive days.

Official Title
-----------------
A Double-Masked, Randomized, Placebo-Controlled Study of Trabecular Outflow Facility Following Treatment With Netarsudil Ophthalmic Solution 0.02% (AR-13324) in Subjects With Elevated Intraocular Pressure

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

Intervention / Treatment
-----------------
* Drug: Netarsudil Ophthalmic Solution 0.02%
* Other: Placebo Comparator


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must be 18 years of age or older Diagnosis of open primary angle glaucoma(POAG) or ocular hypertension (OHT) in both eyes Unmedicated intraocular pressure (IOP) >20 mmHg and < 30 mmHg in both eyes at first qualification visit Best corrected visual acuity (BCVA) equivalent to 20/200 Snellen or better Able to give informed consent and follow study instructions Exclusion Criteria: Ophthalmic: Clinically significant ocular disease Pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure glaucoma, or narrow angles Intraocular pressure ≥30 mmHg in either eye A difference in IOP between eyes >4mmHg at qualification visit Use of more than two ocular hypotensive medications within 30 days of screening Known hypersensitivity to any component of the formulation Previous glaucoma surgery or refractive surgery Keratorefractive surgery in either eye Report of ocular injury in either eye within the six months prior to screening or ocular or non-refractive surgery within 3 months prior to screening Recent or current ocular infection or inflammation in either eye Use of ocular medication in either eye of any kind within 30 days of screening Mean central corneal thickness greater than 620 μm in either eye Any abnormality preventing reliable applanation tonometry of either eye Lack of suitable episcleral vein prior to performing Episcleral Venus Pressure (EVP) measurement (applicable to 1 site only) Systemic: Clinically significant abnormalities within 6 weeks prior to screening Clinically significant systemic disease Participation in any investigational study within 60 days prior to screening Use of systemic medication that could have an effect on intraocular pressure within 30 days prior to screening Women of childbearing potential who were pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control

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
Interventional Model Description: Paired comparison study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Netarsudil Ophthalmic Solution 0.02%<br>Netarsudil Ophthalmic Solution 0.02% was administered in one eye and Placebo comparator in contralateral eye | Drug: Netarsudil Ophthalmic Solution 0.02%<br>* 1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye<br>Other: Placebo Comparator<br>* 1 drop daily (QD), in the morning (AM) of Placebo comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye<br>|
| Placebo Comparator: Placebo Comparator<br>Placebo comparator administered in one eye and Netarsudil Ophthalmic Solution 0.02% in contralateral eye | Drug: Netarsudil Ophthalmic Solution 0.02%<br>* 1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye<br>Other: Placebo Comparator<br>* 1 drop daily (QD), in the morning (AM) of Placebo comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility | Mean diurnal change from baseline in trabecular (tonographic) outflow facility. | Study treatment was administered for 7 days, and outcome measures collected on Day 8 | 
| Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility. | Mean diurnal change from baseline in trabecular (tonographic) outflow facility. | Study treatment was administered for 7 days, and outcome measures collected on Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants) | Study treatment was administered for 7 days, and outcome measures collected on Day 8 | 
| Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants) | Study treatment was administered for 7 days, and outcome measures collected on Day 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aqueous Humor Dynamics, Trabecular Outflow, Netarsudil