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

• Sponsor: Aerie Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03233308
• Collaborator: (none)
• Enrollment: 20
• Locations: 2
• Arms: 2
• Actual Duration (Months): 5.9
• Patients Per Site: 10
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

To evaluate the effect on trabecular outflow facility of Netarsudil ophthalmic solution 0.02% compared to placebo

Condition or Disease	Intervention/Treatment	Phase
Primary Open Angle Glaucoma or Ocular Hypertension	Drug: Netarsudil Ophthalmic Solution 0.02%; Other: Placebo Comparator	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Paired comparison studyPaired comparison study
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 20, 2017
• Actual Primary Completion Date: Apr 19, 2018
• Actual Study Completion Date: Apr 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Netarsudil Ophthalmic Solution 0.02% Netarsudil Ophthalmic Solution 0.02% was administered in one eye and Placebo comparator in contralateral eye	Drug: Netarsudil Ophthalmic Solution 0.02%; 1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye; Other: Placebo Comparator; 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
Placebo Comparator: Placebo Comparator Placebo comparator administered in one eye and Netarsudil Ophthalmic Solution 0.02% in contralateral eye	Drug: Netarsudil Ophthalmic Solution 0.02%; 1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye; Other: Placebo Comparator; 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

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility [Study treatment was administered for 7 days, and outcome measures collected on Day 8]

   Mean diurnal change from baseline in trabecular (tonographic) outflow facility.

2. Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility. [Study treatment was administered for 7 days, and outcome measures collected on Day 8]

   Mean diurnal change from baseline in trabecular (tonographic) outflow facility.

Secondary Outcome Measures

1. Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) [Study treatment was administered for 7 days, and outcome measures collected on Day 8]

   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)

2. Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) [Study treatment was administered for 7 days, and outcome measures collected on Day 8]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Must be 18 years of age or older

2. Diagnosis of open primary angle glaucoma(POAG) or ocular hypertension (OHT) in both eyes

3. Unmedicated intraocular pressure (IOP) >20 mmHg and < 30 mmHg in both eyes at first qualification visit

4. Best corrected visual acuity (BCVA) equivalent to 20/200 Snellen or better

5. Able to give informed consent and follow study instructions

Exclusion Criteria:

Ophthalmic:

1. Clinically significant ocular disease

2. Pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure glaucoma, or narrow angles

3. Intraocular pressure ≥30 mmHg in either eye

4. A difference in IOP between eyes >4mmHg at qualification visit

5. Use of more than two ocular hypotensive medications within 30 days of screening

6. Known hypersensitivity to any component of the formulation

7. Previous glaucoma surgery or refractive surgery

8. Keratorefractive surgery in either eye

9. 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

10. Recent or current ocular infection or inflammation in either eye

11. Use of ocular medication in either eye of any kind within 30 days of screening

12. Mean central corneal thickness greater than 620 μm in either eye

13. Any abnormality preventing reliable applanation tonometry of either eye

14. Lack of suitable episcleral vein prior to performing Episcleral Venus Pressure (EVP) measurement (applicable to 1 site only)

Systemic:

1. Clinically significant abnormalities within 6 weeks prior to screening

2. Clinically significant systemic disease

3. Participation in any investigational study within 60 days prior to screening

4. Use of systemic medication that could have an effect on intraocular pressure within 30 days prior to screening

5. Women of childbearing potential who were pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905
2	Duke Eye Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Aerie Pharmaceuticals

Investigators

• Study Director: Nancy Ramirez-Davis, Aerie Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 16, 2017
• Statistical Analysis Plan - Feb 5, 2018

More Information

Publications

None provided.

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03233308
• Other Study ID Numbers: AR-13324-CS206
• First Posted: Jul 28, 2017
• Last Update Posted: Aug 6, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Aerie Pharmaceuticals: Aqueous Humor Dynamics; Trabecular Outflow; Netarsudil
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	All Randomized Patients
Arm/Group Description	1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye
Period Title: Overall Study
STARTED	20
COMPLETED	18
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	All Randomized Patients
Arm/Group Description	1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and placebo comparator to the contralateral eye
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 45%
>=65 years	11 55%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (12.53)
Sex: Female, Male (Count of Participants)
Female	14 70%
Male	6 30%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%
Not Hispanic or Latino	19 95%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 25%
White	14 70%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population

Arm/Group Title	Netarsudil Ophthalmic Solution 0.02%	Placebo Comparator
Arm/Group Description	Netarsudil Ophthalmic Solution 0.02% was administered in one eye	Placebo Comparator administered in contralateral eye
Measure Participants	18	18
Mean (Standard Deviation) [mcl/min/mmHg]	0.039 (0.0401)	0.007 (0.0275)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Netarsudil Ophthalmic Solution 0.02%
	Comments	Mean Change from Baseline
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	t-test, 1 sided
	Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population

Arm/Group Title	Netarsudil Ophthalmic Solution 0.02%	Placebo Comparator
Arm/Group Description	Netarsudil Ophthalmic Solution 0.02% was administered in one eye	Placebo comparator administered in contralateral eye
Measure Participants	18	18
Mean (Standard Deviation) [percentage change]	34.589 (34.5935)	9.597 (25.6334)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Netarsudil Ophthalmic Solution 0.02%
	Comments	Mean change from baseline (percent difference from baseline)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	t-test, 1 sided
	Comments

3. Secondary Outcome

Title	Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)
Description	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)
Time Frame	Study treatment was administered for 7 days, and outcome measures collected on Day 8

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population, EVP analyzed in 9 participants

Arm/Group Title	Netarsudil Ophthalmic Solution 0.02%	Placebo Comparator
Arm/Group Description	Netarsudil Ophthalmic Solution 0.02% administered to one eye and placebo to the contralateral eye	Placebo Comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye
Measure Participants	18	18
Diurnal EVP (delta vs.baseline)	-0.787 (0.8372)	0.103 (0.7094)
Diurnal IOP (delta vs.baseline)	-4.521 (1.5842)	-0.979 (1.6009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Netarsudil Ophthalmic Solution 0.02%
	Comments	Mean change from baseline -EVP
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0687
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Netarsudil Ophthalmic Solution 0.02%
	Comments	Mean change from baseline -IOP
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 1 sided
	Comments

4. Secondary Outcome

Title	Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)
Description	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)
Time Frame	Study treatment was administered for 7 days, and outcome measures collected on Day 8

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population, EVP analyzed in 9 participants

Arm/Group Title	Netarsudil Ophthalmic Solution 0.02%	Placebo Comparator
Arm/Group Description	Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye	Placebo comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye
Measure Participants	18	18
Percent change from baseline (EVP)	-9.465 (9.5044)	3.103 (7.7322)
Percent change from baseline (IOP)	-19.568 (6.0713)	-4.227 (6.9699)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Netarsudil Ophthalmic Solution 0.02%
	Comments	Mean change from baseline (percent difference from baseline) -EVP
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0087
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Netarsudil Ophthalmic Solution 0.02%
	Comments	Mean change from baseline (percent difference from baseline)- IOP
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 1 sided
	Comments

Adverse Events

Time Frame	7 Days
Arm/Group Title	Netarsudil Ophthalmic Solution 0.02%		Placebo Comparator
Arm/Group Description	Netarsudil Ophthalmic Solution 0.02% was administered in one eye and Placebo comparator in contralateral eye		Placebo comparator was administered in one eye and Netarsudil Ophthalmic Solution 0.02% in contralateral eye
All Cause Mortality
	Netarsudil Ophthalmic Solution 0.02%		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Netarsudil Ophthalmic Solution 0.02%		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Netarsudil Ophthalmic Solution 0.02%		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/20 (65%)		0/20 (0%)
Eye disorders
Conjunctival Hyperaemia	13/20 (65%)	13	0/20 (0%)	0
Eye Irritation	3/20 (15%)	3	0/20 (0%)	0
Vision Blurred	2/20 (10%)	2	0/20 (0%)	0
Eye Swelling	1/20 (5%)	1	0/20 (0%)	0
Photophobia	1/20 (5%)	1	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.