Efficacy and Systemic Safety of Netarsudil 0.01%, 0.02%, 0.04% Relative to Placebo in Subjects With Open-angle Glaucoma or Ocular Hypertension in Japan

• Sponsor: Aerie Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03844945
• Collaborator: (none)
• Enrollment: 215
• Locations: 25
• Arms: 4
• Actual Duration (Months): 6
• Patients Per Site: 8.6
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

Test ocular hypotensive efficacy and systemic safety of netarsudil 0.01%, 0.02%, 0.04% relative to placebo in subjects with open-angle glaucoma or ocular hypertension in Japan

Condition or Disease	Intervention/Treatment	Phase
Open Angle Glaucoma; Ocular Hypertension	Drug: Netarsudil Ophthalmic Solution 0.01%; Drug: Netarsudil Ophthalmic Solution 0.02%; Drug: Netarsudil Ophthalmic Solution 0.04%; Other: Netarsudil Ophthalmic Solution Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 215 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Prospective, Double-masked, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Assessing the Safety, Ocular Hypotensive Efficacy and Optimum Dose Concentration to be Used Clinically of Netarsudil Ophthalmic Solution in Subjects With Open-angle Glaucoma or Ocular Hypertension in Japan
• Actual Study Start Date: Mar 19, 2019
• Actual Primary Completion Date: Sep 19, 2019
• Actual Study Completion Date: Sep 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Netarsudil Ophthalmic Solution 0.01% 1 drop daily into each eye in the evening for 28 days	Drug: Netarsudil Ophthalmic Solution 0.01%; Topical sterile ophthalmic solution
Experimental: Netarsudil Ophthalmic Solution 0.02% 1 drop daily into each eye in the evening for 28 days	Drug: Netarsudil Ophthalmic Solution 0.02%; Topical sterile ophthalmic solution; Other Names: Rhopressa®
Experimental: Netarsudil Ophthalmic Solution 0.04% 1 drop daily into each eye in the evening for 28 days	Drug: Netarsudil Ophthalmic Solution 0.04%; Topical sterile ophthalmic solution
Placebo Comparator: Netarsudil Ophthalmic Solution Placebo 1 drop daily into each eye in the evening for 28 days	Other: Netarsudil Ophthalmic Solution Placebo; Topical sterile ophthalmic solution

Outcome Measures

Primary Outcome Measures

1. Intraocular Pressure (IOP) [29 Days]

   Mean diurnal IOP within a treatment by Goldman Applanation Tonometry

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Must be 20 years of age or older

2. Diagnosis of open-angle glaucoma (OAG) or ocular hypertension (OHT) in both eyes. (OAG in one eye and OHT in the fellow eye is acceptable)

3. BCVA 0.1 or better in decimal unit using Landolt-C chart or its equivalent

4. Able and willing to give signed informed consent and following study instructions

Exclusion Criteria:

1. Clinically significant ocular diseases

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

3. Previous glaucoma intraocular surgery

4. Refractive surgery in either eye

5. Ocular trauma

6. Ocular infection or inflammation

7. Known hypersensitivity to benzalkonium chloride or excipient of netarsudil ophthalmic solution

8. Cannot demonstrate proper delivery of the eye drop

9. Clinically significant abnormalities in screen lab tests

10. Clinically significant systemic disease

11. Participation in any investigational study within 30 days of screening

12. Women of child-bearing potential 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	Nomura Eye Clinic	Ichinomiya-shi	Aichi	Japan
2	Shisui ophthalmology clinic	Shisui	Chiba	Japan
3	Nakamori Eye Clinic	Kitakyushu-shi	Fukuoka	Japan
4	Southern TOHOKU Eye Clinic	Koriyama-shi	Fukushima	Japan
5	Kusatsu Eye Clinic	Hiroshima-shi	Hiroshima	Japan
6	Kanamori Eye Clinic	Akashi-shi	Hyogo	Japan
7	Sameshima Eye Clinic	Kagoshima-shi	Kagoshima	Japan
8	Asahigaoka Ophthalmology	Sendai-shi	Miyagi	Japan
9	Sugao Eye Clinic	Osaka-shi	Osaka	Japan
10	Yubikai Kawaguchi Aozora Eye Clinic	Kawaguchi-shi	Saitama-Ken	Japan
11	Hangai Eye Institute	Saitama-shi	Saitama	Japan
12	Omiya Hamada Eye Clinic West Entrance Branch	Saitama-shi	Saitama	Japan
13	Omiya Hamada Eye Clinic	Saitama-shi	Saitama	Japan
14	Shibuya Ophthalmology Clinic	Saitama-shi	Saitama	Japan
15	Yoshimura Eye & Internal Medical Clinic	Mishima	Shiizuoka	Japan
16	Medical Corporation Muramatsu Clinic Muramatsu Eye Clinic	Susono	Shizuoka-ken	Japan
17	Ueda Eye Clinic	Arakawa-ku	Tokyo	Japan
18	Ochanomizu Inoue Eye Clinic	Chiyoda-ku	Tokyo	Japan
19	Kiyosawa Eye Clinic	Koto-Ku	Tokyo	Japan
20	Tamagawa Eye Clinic	Ota-ku	Tokyo	Japan
21	Seijo Clinic	Setagaya-Ku	Tokyo	Japan
22	Dogenzaka Kato Eye Clinic	Shibuya-ku	Tokyo	Japan
23	Wakabadai Eye Clinic	Shibuya-ku	Tokyo	Japan
24	Hashida Eye Clinic	Shinagawa-Ku	Tokyo	Japan
25	Watanabe Eye Clinic	Shinagawa-Ku	Tokyo	Japan

Sponsors and Collaborators

• Aerie Pharmaceuticals

Investigators

• Study Director: Kenji Aso, M.D., Ph.D., Aerie Pharmaceuticals Ireland Ltd. (Japan Branch)

Study Documents (Full-Text)

• Study Protocol - Dec 6, 2018
• Statistical Analysis Plan - Jun 16, 2020

More Information

Publications

None provided.

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03844945
• Other Study ID Numbers: AR-13324-CS208
• First Posted: Feb 19, 2019
• Last Update Posted: Oct 19, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Aerie Pharmaceuticals: Glaucoma; Ocular Hypertension; Open-Angle Glaucoma
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Pharmaceutical Solutions; Ophthalmic Solutions

Study Results

Participant Flow

Recruitment Details	Participants were recruited at 25 clinical trial sites in Japan.
Pre-assignment Detail	Prior to enrollment, adult participants were to have a Screening Visit and 2 Qualification Visits to allow for washout of ocular hypotensive medication if needed.

Arm/Group Title	Netarsudil Ophthalmic Solution 0.01%	Netarsudil Ophthalmic Solution 0.02%	Netarsudil Ophthalmic Solution 0.04%	Netarsudil Ophthalmic Solution Placebo
Arm/Group Description	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution
Period Title: Overall Study
STARTED	55	54	51	55
COMPLETED	54	53	46	54
NOT COMPLETED	1	1	5	1

Baseline Characteristics

Arm/Group Title	Netarsudil Ophthalmic Solution 0.01%	Netarsudil Ophthalmic Solution 0.02%	Netarsudil Ophthalmic Solution 0.04%	Netarsudil Ophthalmic Solution Placebo	Total
Arm/Group Description	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution	Total of all reporting groups
Overall Participants	55	54	51	55	215
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.7 (14.62)	64.1 (12.16)	62 (13.56)	64.6 (12.58)	63.35 (13.23)
Sex: Female, Male (Count of Participants)
Female	36 65.5%	29 53.7%	27 52.9%	31 56.4%	123 57.2%
Male	19 34.5%	25 46.3%	24 47.1%	24 43.6%	92 42.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	55 100%	54 100%	51 100%	55 100%	215 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Intraocular Pressure (IOP)
Description	Mean diurnal IOP within a treatment by Goldman Applanation Tonometry
Time Frame	29 Days

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population

Arm/Group Title	Netarsudil Ophthalmic Solution 0.01%	Netarsudil Ophthalmic Solution 0.02%	Netarsudil Ophthalmic Solution 0.04%	Netarsudil Ophthalmic Solution Placebo
Arm/Group Description	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution
Measure Participants	55	54	51	55
Day 1	20.5 (2.8362)	20.3 (2.8039)	20.8 (3.2037)	21.1 (3.7023)
Day 8	16.2 (2.568)	15.9 (2.673)	15.7 (4.014)	19.8 (4.059)
Day 15	15.9 (2.703)	15.6 (2.573)	15.7 (4.190)	19.3 (3.702)
Day 29	16.3 (2.609)	15.4 (2.411)	16.2 (4.496)	19.3 (3.728)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Netarsudil Ophthalmic Solution 0.01%, Netarsudil Ophthalmic Solution 0.02%, Netarsudil Ophthalmic Solution 0.04%, Netarsudil Ophthalmic Solution Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Ocular/Systemic safety during a 4-week treatment period
Adverse Event Reporting Description	Safety population, defined as all randomized subjects who received at least one dose of study drug.
Arm/Group Title	Netarsudil Ophthalmic Solution 0.01%		Netarsudil Ophthalmic Solution 0.02%		Netarsudil Ophthalmic Solution 0.04%		Netarsudil Ophthalmic Solution Placebo
Arm/Group Description	1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.01%: Topical sterile ophthalmic solution		1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.02%: Topical sterile ophthalmic solution		1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution 0.04%: Topical sterile ophthalmic solution		1 drop daily into each eye in the evening for 28 days Netarsudil Ophthalmic Solution Placebo: Topical sterile ophthalmic solution
All Cause Mortality
	Netarsudil Ophthalmic Solution 0.01%		Netarsudil Ophthalmic Solution 0.02%		Netarsudil Ophthalmic Solution 0.04%		Netarsudil Ophthalmic Solution Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Serious Adverse Events
	Netarsudil Ophthalmic Solution 0.01%		Netarsudil Ophthalmic Solution 0.02%		Netarsudil Ophthalmic Solution 0.04%		Netarsudil Ophthalmic Solution Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Other (Not Including Serious) Adverse Events
	Netarsudil Ophthalmic Solution 0.01%		Netarsudil Ophthalmic Solution 0.02%		Netarsudil Ophthalmic Solution 0.04%		Netarsudil Ophthalmic Solution Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/55 (38.2%)		27/54 (50%)		36/51 (70.6%)		5/55 (9.1%)
Eye disorders
Conjunctival Hyperemia	13/55 (23.6%)		20/54 (37%)		29/51 (56.9%)		1/55 (1.8%)
Eye Irritation	3/55 (5.5%)		5/54 (9.3%)		2/51 (3.9%)		0/55 (0%)
Conjunctival Hemorrhage	0/55 (0%)		3/54 (5.6%)		3/51 (5.9%)		0/55 (0%)
Eye Discharge	1/55 (1.8%)		1/54 (1.9%)		1/51 (2%)		0/55 (0%)
Punctate keratitis	1/55 (1.8%)		0/54 (0%)		1/51 (2%)		1/55 (1.8%)
Vision blurred	1/55 (1.8%)		1/54 (1.9%)		1/51 (2%)		0/55 (0%)
Abnormal sensation in eye	0/55 (0%)		1/54 (1.9%)		0/51 (0%)		1/55 (1.8%)
Eye pain	0/55 (0%)		0/54 (0%)		2/51 (3.9%)		0/55 (0%)
Visual acuity reduced	0/55 (0%)		1/54 (1.9%)		1/51 (2%)		0/55 (0%)
Blepharitis	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Chalazion	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Conjunctival follicles	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Corneal erosion	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Dry eye	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Erythema of eyelid	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Iritis	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Keratitis	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Lacrimation increased	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Retinal exudates	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Retinal tear	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Swelling of eyelid	0/55 (0%)		1/54 (1.9%)		0/51 (0%)		0/55 (0%)
Trichiasis	0/55 (0%)		0/54 (0%)		0/51 (0%)		1/55 (1.8%)
Ulcerative keratitis	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Vernal keratoconjuncitvitis	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Visual acuity reduced transiently	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Gastrointestinal disorders
Toothache	0/55 (0%)		0/54 (0%)		0/51 (0%)		1/55 (1.8%)
General disorders
Instillation site foreign body sensation	0/55 (0%)		1/54 (1.9%)		1/51 (2%)		0/55 (0%)
Instillation site pain	0/55 (0%)		1/54 (1.9%)		0/51 (0%)		0/55 (0%)
Hepatobiliary disorders
Hepatic function abnormal	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Infections and infestations
Conjunctivitis	2/55 (3.6%)		0/54 (0%)		2/51 (3.9%)		0/55 (0%)
Nasopharyngitis	0/55 (0%)		2/54 (3.7%)		3/51 (5.9%)		0/55 (0%)
Cystitis	0/55 (0%)		1/54 (1.9%)		0/51 (0%)		0/55 (0%)
Gastritis bacterial	0/55 (0%)		0/54 (0%)		1/51 (2%)		0/55 (0%)
Gastroenteritis	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Gingivitis	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Injury, poisoning and procedural complications
Corneal abrasion	0/55 (0%)		1/54 (1.9%)		0/51 (0%)		0/55 (0%)
Investigations
Intraocular pressure increased	0/55 (0%)		0/54 (0%)		1/51 (2%)		1/55 (1.8%)
Urine leukocyte esterase positive	0/55 (0%)		1/54 (1.9%)		0/51 (0%)		0/55 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/55 (0%)		1/54 (1.9%)		1/51 (2%)		0/55 (0%)
Osteoarthritis	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Nervous system disorders
Dizziness	1/55 (1.8%)		0/54 (0%)		0/51 (0%)		0/55 (0%)
Renal and urinary disorders
Urine abnormality	0/55 (0%)		1/54 (1.9%)		0/51 (0%)		0/55 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Prior to publishing any trial results, site shall provide the to be published information to the Sponsor for review and obtain written approval at least thirty (30) days in advance of publication.