Double-masked Study of Netarsudil (AR-13324) Ophthalmic Solution in Subjects With Glaucoma or Ocular Hypertension

• Sponsor: Aerie Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02558374
• Collaborator: (none)
• Enrollment: 708
• Location: 1
• Arms: 2
• Duration (Months): 15
• Patients Per Site Per Month: 47.2

Study Details

Study Description

Brief Summary

To evaluate ocular hypotensive efficacy and safety of Netarsudil (AR-13324) Ophthalmic Solution compared to Timolol Maleate Ophthalmic Solution.

Condition or Disease	Intervention/Treatment	Phase
Open-angle Glaucoma; Ocular Hypertension	Drug: AR-13324 Ophthalmic Solution 0.02%; Drug: Timolol Maleate Ophthalmic Solution 0.5% BID; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 708 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-masked, Randomized, Multi-center, Active-controlled, Parallel Group, 6-month Study With a 3-month Interim Analysis Assessing the Ocular Hypotensive Efficacy and Safety of AR-13324 Ophthalmic Solution, 0.02% QD Compared to Timolol Maleate Ophthalmic Solution, 0.5% BID in Patients With Elevated Intraocular Pressure
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AR-13324 Ophthalmic Solution 0.02% & placebo 1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU)	Drug: AR-13324 Ophthalmic Solution 0.02%; 1 drop once daily (QD), PM, OU; Other Names: Netarsudil ; Other: Placebo; 1 drop QD, AM, OU
Active Comparator: Timolol Maleate Ophthalmic Solution 0.5% BID 1 drop twice daily (BID) in the morning (AM) & evening (PM) in both eyes (OU)	Drug: Timolol Maleate Ophthalmic Solution 0.5% BID; 1 drop BID, AM/PM, OU

Outcome Measures

Primary Outcome Measures

1. IOP (Intraocular Pressure) [3 months]

   The primary efficacy outcome is mean IOP

Secondary Outcome Measures

1. Extent of Exposure [6 months]

   Exposure to study medication in days for all treatment groups

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. 18 years of age or older

2. Diagnosis of open angle glaucoma or ocular hypertension in both eyes

3. Post-washout intraocular pressure >20mmHg and <30mmHg in 1 or both eyes at 2 qualification visits

4. Corrected visual acuity equivalent to 20/200

5. Able to give informed consent and follow study instructions

Exclusion Criteria:

1. Clinically significant ocular disease

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

3. Unmedicated intraocular pressure ≥30mmHg

4. Use of more than 2 ocular hypotensive medications within 30 days of screening

5. Known hypersensitivity to any component of the formulation

6. Previous glaucoma surgery or refractive surgery

7. Ocular trauma within 6 months prior to screening

8. Any ocular surgery or non-refractive laser treatment within 3 months prior to screening

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

10. Used ocular medication in either eye of any kind within 30 days of screening

11. Mean central corneal thickness >620µm at screening

12. Any abnormality preventing reliable applanation tonometry of either eye

13. Clinically significant abnormalities in lab tests at screening

14. Known hypersensitivity or contraindication to beta-adrenoceptor antagonists

15. Clinically significant systemic disease

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

17. Used any systemic medication that could have a substantial effect in intraocular pressure within 30 days prior to screening

18. Women who are 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	Aerie Pharmaceuticals	Bedminster	New Jersey	United States	07921

Sponsors and Collaborators

• Aerie Pharmaceuticals

Investigators

• Study Director: Theresa Heah, MD, Aerie Pharmaceuticals, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02558374
• Other Study ID Numbers: AR-13324-CS304
• First Posted: Sep 24, 2015
• Last Update Posted: Apr 6, 2018
• Last Verified: Jan 1, 2018

• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Timolol; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Recruitment Details	Participants were recruited at 53 sites starting in September 2015

Arm/Group Title	AR-13324 Ophthalmic Solution 0.02% & Placebo	Timolol Maleate Ophthalmic Solution 0.5% BID
Arm/Group Description	1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU)	1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
Period Title: Overall Study
STARTED	351	357
COMPLETED	243	314
NOT COMPLETED	108	43

Baseline Characteristics

Arm/Group Title	AR-13324 Ophthalmic Solution 0.02% & Placebo	Timolol Maleate Ophthalmic Solution 0.5% BID	Total
Arm/Group Description	1 drop AR-13324 in the evening (PM) and 1 drop placebo in the morning (AM) in both eyes (OU)	1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)	Total of all reporting groups
Overall Participants	351	357	708
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (11.55)	64.5 (10.97)	64.3 (11.25)
Sex: Female, Male (Count of Participants)
Female	208 59.3%	237 66.4%	445 62.9%
Male	143 40.7%	120 33.6%	263 37.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	89 25.4%	87 24.4%	176 24.9%
Not Hispanic or Latino	262 74.6%	270 75.6%	532 75.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	7 2%	6 1.7%	13 1.8%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.3%	1 0.1%
Black or African American	84 23.9%	75 21%	159 22.5%
White	259 73.8%	274 76.8%	533 75.3%
More than one race	0 0%	1 0.3%	1 0.1%
Unknown or Not Reported	1 0.3%	0 0%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	IOP (Intraocular Pressure)
Description	The primary efficacy outcome is mean IOP
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Per-Protocol Population

Arm/Group Title	AR-13324 Ophthalmic Solution 0.02% & Placebo	Timolol Maleate Ophthalmic Solution 0.5% BID
Arm/Group Description	1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU)	1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
Measure Participants	306	316
Day 1, 0800 hours	23.93 (2.441)	23.89 (2.318)
Day 1, 1000 hours	22.67 (2.826)	22.77 (2.565)
Day 1, 1600 hours	22.17 (2.857)	22.04 (2.708)
Day 15, 0800 hours	19.20 (3.833)	18.60 (3.396)
Day 15, 1000 hours	17.93 (3.678)	17.80 (3.237)
Day 15, 1600 hours	17.76 (3.527)	17.85 (3.102)
Day 43, 0800 hours	19.45 (3.929)	18.52 (3.316)
Day 43, 1000 hours	18.12 (3.560)	17.89 (3.157)
Day 43, 1600 hours	17.89 (3.438)	17.88 (3.356)
Day 90, 0800 hours	19.24 (3.889)	18.35 (3.196)
Day 90, 1000 hours	18.30 (3.637)	17.60 (3.173)
Day 90, 1600 hours	18.02 (3.644)	17.66 (3.080)

2. Secondary Outcome

Title	Extent of Exposure
Description	Exposure to study medication in days for all treatment groups
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	AR-13324 Ophthalmic Solution 0.02% & Placebo	Timolol Maleate Ophthalmic Solution 0.5% BID
Arm/Group Description	1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU)	1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
Measure Participants	351	357
Mean (Standard Deviation) [days]	147.4 (54.47)	167.7 (36.40)

Adverse Events

Time Frame	6 months
Arm/Group Title	AR-13324 Ophthalmic Solution 0.02% & Placebo		Timolol Maleate Ophthalmic Solution 0.5% BID
Arm/Group Description	1 drop AR-13324 in the evening (PM) & 1 drop placebo in the morning (AM) in both eyes (OU)		1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU)
All Cause Mortality
	AR-13324 Ophthalmic Solution 0.02% & Placebo		Timolol Maleate Ophthalmic Solution 0.5% BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/351 (0.3%)		0/357 (0%)
Serious Adverse Events
	AR-13324 Ophthalmic Solution 0.02% & Placebo		Timolol Maleate Ophthalmic Solution 0.5% BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/351 (2.3%)		10/357 (2.8%)
Cardiac disorders
Atrial Fibrillation	0/351 (0%)		1/357 (0.3%)
Cardiac Arrest	1/351 (0.3%)		0/357 (0%)
Cardiomegaly	0/351 (0%)		1/357 (0.3%)
Coronary Artery Disease	0/351 (0%)		1/357 (0.3%)
Myocardial Infarction	1/351 (0.3%)		0/357 (0%)
Gastrointestinal disorders
Abdominal Discomfort	0/351 (0%)		1/357 (0.3%)
Gastric Volvulus	1/351 (0.3%)		0/357 (0%)
Hiatus Hernia	1/351 (0.3%)		0/357 (0%)
Infections and infestations
Pneumonia	0/351 (0%)		1/357 (0.3%)
Injury, poisoning and procedural complications
Fall	0/351 (0%)		1/357 (0.3%)
Radius Fracture	0/351 (0%)		1/357 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Cancer Recurrent	1/351 (0.3%)		0/357 (0%)
Chronic Myeloid Leukaemia	1/351 (0.3%)		0/357 (0%)
Invasive Ductal Breast Carcinoma	0/351 (0%)		1/357 (0.3%)
Papillary Thyroid Cancer	1/351 (0.3%)		0/357 (0%)
Uterine Leiomyoma	0/351 (0%)		1/357 (0.3%)
Nervous system disorders
Transient Ischaemic Attack	1/351 (0.3%)		1/357 (0.3%)
Facial Paralysis	0/351 (0%)		1/357 (0.3%)
Psychiatric disorders
Mental Status Changes	0/351 (0%)		1/357 (0.3%)
Renal and urinary disorders
Bladder Prolapse	1/351 (0.3%)		0/357 (0%)
Reproductive system and breast disorders
Cervical Dysplasia	1/351 (0.3%)		0/357 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration	1/351 (0.3%)		0/357 (0%)
Other (Not Including Serious) Adverse Events
	AR-13324 Ophthalmic Solution 0.02% & Placebo		Timolol Maleate Ophthalmic Solution 0.5% BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	245/351 (69.8%)		139/357 (38.9%)
Eye disorders
Conjunctival Hyperaemia	168/351 (47.9%)		33/357 (9.2%)
Cornea Verticillata	86/351 (24.5%)		0/357 (0%)
Conjunctival Haemorrhage	56/351 (16%)		11/357 (3.1%)
Lacrimation Increased	26/351 (7.4%)		5/357 (1.4%)
Erythema of Eyelid	26/351 (7.4%)		2/357 (0.6%)
Vision Blurred	22/351 (6.3%)		4/357 (1.1%)
General disorders
Instillation Site Pain	83/351 (23.6%)		92/357 (25.8%)
Instillation Site Erythema	36/351 (10.3%)		4/357 (1.1%)
Investigations
Vital Dye Staining Cornea Present	34/351 (9.7%)		24/357 (6.7%)

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.