Double-masked Study of PG324 Ophthalmic Solution in Patients With Open-angle Glaucoma or Ocular Hypertension

• Sponsor: Aerie Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02674854
• Collaborator: (none)
• Enrollment: 750
• Location: 1
• Arms: 3
• Duration (Months): 12.9
• Patients Per Site Per Month: 57.9

Study Details

Study Description

Brief Summary

To evaluate ocular hypotensive efficacy and safety of PG324 Ophthalmic Solution compared to netarsudil (AR-13324) ophthalmic solution 0.02% and latanoprost ophthalmic solution 0.005%

Condition or Disease	Intervention/Treatment	Phase
Open-angle Glaucoma; Ocular Hypertension	Drug: PG324 Ophthalmic Solution 0.02%/0.005%; Drug: Netarsudil (AR-13324) ophthalmic solution 0.02%; Drug: Latanoprost ophthalmic solution 0.005%	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 750 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Prospective, Double-masked, Randomized, Multi-center, Active Controlled, Parallel-group, 3-month Study Assessing the Safety and Ocular Hypotensive Efficacy of PG324 Ophthalmic Solution Compared to AR-13324 Ophthalmic Solution 0.02% and Latanoprost Ophthalmic Solution 0.005% in Subjects With Elevated Intraocular Pressure
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: Mar 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PG324 Ophthalmic Solution 0.02%/0.005% Fixed combination of netarsudil 0.02%, latanoprost 0.005 % ophthalmic solution	Drug: PG324 Ophthalmic Solution 0.02%/0.005%; 1 drop daily in the evening (PM) in both eyes (OU)
Active Comparator: Netarsudil (AR-13324) ophthalmic solution 0.02% Netarsudil 0.02% ophthalmic solution	Drug: Netarsudil (AR-13324) ophthalmic solution 0.02%; 1 drop daily in the evening (PM) in both eyes (OU)
Active Comparator: Latanoprost ophthalmic solution 0.005% Latanoprost 0.005 % ophthalmic solution	Drug: Latanoprost ophthalmic solution 0.005%; 1 drop daily in the evening (PM) in both eyes (OU)

Outcome Measures

Primary Outcome Measures

1. Intraocular Pressure (IOP) [3 months]

   Mean intraocular pressure(IOP) at 08:00, 10:00 and 16:00 hours, at Day 15, Day 43 and Day 90, as measured by Goldmann applanation tonometry.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18 years of age or older (19 years of age or older in Canada)

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

3. Unmedicated intraocular pressure >20mmHg and <36mmHg in both eyes at 2 qualification visits

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 or narrow angles

3. Unmedicated intraocular pressure ≥36mmHg in either eye or use of more than 2 ocular hypotensive medications within 30 days of screening

4. Known hypersensitivity to any component of the formulation or latanoprost

5. Previous glaucoma surgery or refractive surgery

6. Ocular trauma within 6 months prior to screening

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

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

9. Use of ocular medication in either eye of any kind within 30 days of screening and throughout of the study

10. Mean central corneal thickness >620µm at screening in either eye

11. Any abnormality preventing reliable applanation tonometry of either eye

Systemic:

1. Clinically significant abnormalities in lab tests at screening

2. Clinically significant systemic disease

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

4. Systemic medication that could have had a substantial effect on IOP within 30 days prior to screening, or anticipated to be used during the study

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	Aerie Pharmaceuticals	Bedminster	New Jersey	United States	07921

Sponsors and Collaborators

• Aerie Pharmaceuticals

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Apr 8, 2016
• Statistical Analysis Plan - Jan 30, 2017

More Information

Publications

None provided.

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02674854
• Other Study ID Numbers: PG324-CS302
• First Posted: Feb 5, 2016
• Last Update Posted: May 21, 2019
• Last Verified: May 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
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Pharmaceutical Solutions; Latanoprost; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	PG324 Ophthalmic Solution 0.02%/0.005%	Netarsudil (AR-13324) Ophthalmic Solution 0.02%	Latanoprost Ophthalmic Solution 0.005%
Arm/Group Description	1 drop daily in the evening (PM) in both eyes (OU)	1 drop daily in the evening (PM) in both eyes (OU)	1 drop daily in the evening (PM) in both eyes (OU)
Period Title: Overall Study
STARTED	245	255	250
COMPLETED	221	228	236
NOT COMPLETED	24	27	14

Baseline Characteristics

Arm/Group Title	PG324 Ophthalmic Solution	Netarsudil (AR-13324) Ophthalmic Solution 0.02%	Latanoprost Ophthalmic Solution 0.005%	Total
Arm/Group Description	1 drop daily in the evening (PM) in both eyes (OU)	1 drop daily in the evening (PM) in both eyes (OU)	1 drop daily in the evening (PM) in both eyes (OU)	Total of all reporting groups
Overall Participants	245	255	250	750
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	118 48.2%	109 42.7%	112 44.8%	339 45.2%
>=65 years	127 51.8%	146 57.3%	138 55.2%	411 54.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.2 (11.81)	64.5 (10.58)	64.3 (11.41)	64.3 (11.26)
Sex: Female, Male (Count of Participants)
Female	152 62%	153 60%	144 57.6%	449 59.9%
Male	93 38%	102 40%	106 42.4%	301 40.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	45 18.4%	48 18.8%	55 22%	148 19.7%
Not Hispanic or Latino	200 81.6%	207 81.2%	195 78%	602 80.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 0.4%	1 0.1%
Asian	7 2.9%	11 4.3%	6 2.4%	24 3.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	74 30.2%	76 29.8%	79 31.6%	229 30.5%
White	161 65.7%	165 64.7%	163 65.2%	489 65.2%
More than one race	2 0.8%	3 1.2%	0 0%	5 0.7%
Unknown or Not Reported	1 0.4%	0 0%	1 0.4%	2 0.3%

Outcome Measures

1. Primary Outcome

Title	Intraocular Pressure (IOP)
Description	Mean intraocular pressure(IOP) at 08:00, 10:00 and 16:00 hours, at Day 15, Day 43 and Day 90, as measured by Goldmann applanation tonometry.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population with Monte Carlo Markov Chain (MCMC) imputation

Arm/Group Title	PG324 Ophthalmic Solution	Netarsudil (AR-13324) Ophthalmic Solution 0.02%	Latanoprost Ophthalmic Solution 0.005%
Arm/Group Description	1 drop daily in the evening (PM) in both eyes (OU)	1 drop daily in the evening (PM) in both eyes (OU)	1 drop daily in the evening (PM) in both eyes (OU)
Measure Participants	245	255	250
Day 1, 0800 hours	24.69 (3.422)	24.66 (3.148)	24.75 (3.240)
Day 1, 1000 hours	23.33 (3.399)	23.40 (3.538)	23.23 (3.339)
Day 1, 1600 hours	22.37 (3.492)	22.76 (3.558)	22.59 (3.451)
Day 15, 0800 hours	16.06 (3.370)	19.35 (4.279)	18.10 (3.375)
Day 15, 1000 hours	15.31 (3.272)	17.99 (3.909)	17.61 (3.264)
Day 15, 1600 hours	15.16 (3.032)	17.53 (3.772)	17.08 (3.283)
Day 43, 0800 hours	16.43 (3.717)	19.52 (4.273)	17.93 (3.586)
Day 43, 1000 hours	15.54 (3.533)	18.40 (3.810)	17.35 (3.224)
Day 43, 1600 hours	15.45 (3.525)	17.95 (3.776)	17.09 (3.271)
Day 90, 0800 hours	16.45 (3.572)	19.72 (4.419)	17.98 (3.400)
Day 90, 1000 hours	15.58 (3.307)	18.30 (3.846)	17.48 (3.366)
Day 90, 1600 hours	15.52 (3.210)	17.94 (3.627)	17.14 (3.044)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PG324 Ophthalmic Solution, Netarsudil (AR-13324) Ophthalmic Solution 0.02%
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments	PG324 vs. netarsudil

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PG324 Ophthalmic Solution, Latanoprost Ophthalmic Solution 0.005%
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments	PG324 vs. latanoprost

Adverse Events

Time Frame	Adverse event data was collected during the 90 day treatment period.
Adverse Event Reporting Description	Safety population, defined as all randomized subjects who received at least 1 dose of investigational product. One subject was randomized to PG324 ophthalmic solution; however, the subject received latanoprost ophthalmic solution 0.005%, resulting in 1 less subject counted in the safety population for PG324 ophthalmic solution and 1 additional subject in the safety population for latanoprost ophthalmic solution 0.005% relative to the numbers in the respective randomized populations
Arm/Group Title	PG324 Ophthalmic Solution		Netarsudil (AR-13324) Ophthalmic Solution 0.02%		Latanoprost Ophthalmic Solution 0.005%
Arm/Group Description	1 drop daily in the evening (PM) in both eyes (OU)		1 drop daily in the evening (PM) in both eyes (OU)		1 drop daily in the evening (PM) in both eyes (OU)
All Cause Mortality
	PG324 Ophthalmic Solution		Netarsudil (AR-13324) Ophthalmic Solution 0.02%		Latanoprost Ophthalmic Solution 0.005%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/244 (0%)		1/255 (0.4%)		0/251 (0%)
Serious Adverse Events
	PG324 Ophthalmic Solution		Netarsudil (AR-13324) Ophthalmic Solution 0.02%		Latanoprost Ophthalmic Solution 0.005%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/244 (0.8%)		6/255 (2.4%)		5/251 (2%)
Cardiac disorders
Atrial Fibrillation	1/244 (0.4%)	1	2/255 (0.8%)	2	0/251 (0%)	0
Cardiac Failure Congestive	0/244 (0%)	0	1/255 (0.4%)	1	1/251 (0.4%)	1
Cardiac Arrest	0/244 (0%)	0	1/255 (0.4%)	1	0/251 (0%)	0
Coronary Artery Disease	1/244 (0.4%)	1	0/255 (0%)	0	0/251 (0%)	0
Eye disorders
Retinal Detachment	0/244 (0%)	0	0/255 (0%)	0	1/251 (0.4%)	1
Hepatobiliary disorders
Cholecystitis Acute	0/244 (0%)	0	0/255 (0%)	0	1/251 (0.4%)	1
Infections and infestations
Bronchitis	0/244 (0%)	0	1/255 (0.4%)	1	0/251 (0%)	0
Device Related Infection	0/244 (0%)	0	0/255 (0%)	0	1/251 (0.4%)	1
Pneumonia	0/244 (0%)	0	0/255 (0%)	0	1/251 (0.4%)	1
Nervous system disorders
Vertebral Artery Stenosis	0/244 (0%)	0	1/255 (0.4%)	1	0/251 (0%)	0
Psychiatric disorders
Mental Status Changes	1/244 (0.4%)	1	0/255 (0%)	0	0/251 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	0/244 (0%)	0	1/255 (0.4%)	1	0/251 (0%)	0
Other (Not Including Serious) Adverse Events
	PG324 Ophthalmic Solution		Netarsudil (AR-13324) Ophthalmic Solution 0.02%		Latanoprost Ophthalmic Solution 0.005%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	157/244 (64.3%)		143/255 (56.1%)		78/251 (31.1%)
Eye disorders
Conjunctival Hyperaemia	126/244 (51.6%)	126	102/255 (40%)	102	51/251 (20.3%)	51
Cornea Verticillata	32/244 (13.1%)	32	25/255 (9.8%)	25	0/251 (0%)	0
Conjunctival Haemorrhage	14/244 (5.7%)	14	17/255 (6.7%)	17	2/251 (0.8%)	2
Corneal Disorder	14/244 (5.7%)	14	12/255 (4.7%)	12	0/251 (0%)	0
General disorders
Instillation Site Pain	42/244 (17.2%)	42	23/255 (9%)	23	15/251 (6%)	15
Instillation Site Discomfort	15/244 (6.1%)	15	16/255 (6.3%)	16	2/251 (0.8%)	2
Investigations
Vital Dye Staining Cornea Present	8/244 (3.3%)	8	13/255 (5.1%)	13	10/251 (4%)	10

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.