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

• Sponsor: Aerie Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02558400
• Collaborator: (none)
• Enrollment: 718
• Location: 1
• Arms: 3
• Actual Duration (Months): 21.4
• Patients Per Site Per Month: 33.6

Study Details

Study Description

Brief Summary

To evaluate ocular hypotensive efficacy and safety of PG324 Ophthalmic Solution compared to Netarsudil (AR-13324) Ophthalmic Solution and Latanoprost Ophthalmic Solution.

Following completion of the Month 12 study visit procedures, subjects will be offered the opportunity to participate in a 2-month observational (i.e., non-interventional) trial extension.

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: 718 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 12-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
• Actual Study Start Date: Sep 18, 2015
• Actual Primary Completion Date: May 17, 2017
• Actual Study Completion Date: Jun 30, 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 once daily (QD), in the evening (PM) in both eyes (OU)
Active Comparator: AR-13324 Ophthalmic Solution 0.02% Netarsudil 0.02% ophthalmic solution	Drug: Netarsudil (AR-13324) Ophthalmic Solution 0.02%; 1 drop once daily (QD), 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 once daily (QD), in the evening (PM) in both eyes (OU)

Outcome Measures

Primary Outcome Measures

1. Intraocular Pressure (IOP) [Primary efficacy endpoint measured for 3 months (data collected at 08:00, 10:00 and 16:00 hours at Day 15, Day 43 and Day 90)]

   The primary efficacy variable was mean IOP at 08:00, 10:00 and 16:00 hours at Day 15, Day 43 and Day 90, as measured by Goldmann applanation tonometry. Secondary analysis were conducted as a part of safety measurements to month 12 on treatment.

Secondary Outcome Measures

1. Extent of Exposure [12 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. Unmedicated intraocular pressure >20mmHg and <36mmHg in both eyes at 2 qualification visits. Both eyes had to qualify at all qualification visits

4. Corrected visual acuity equivalent to 20/200 Snellen or better

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 ≥36mmHg

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. Clinically significant systemic disease

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

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

17. 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, MBA, Aerie Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Jun 12, 2017
• Statistical Analysis Plan - Jul 20, 2016

More Information

Publications

None provided.

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02558400
• Other Study ID Numbers: PG324-CS301
• First Posted: Sep 24, 2015
• Last Update Posted: Jun 4, 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%	AR-13324 Ophthalmic Solution 0.02%	Latanoprost Ophthalmic Solution 0.005%
Arm/Group Description	PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Netarsudil (AR-13324) Ophthalmic Solution 0.02%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)
Period Title: Overall Study
STARTED	238	244	236
COMPLETED	159	148	203
NOT COMPLETED	79	96	33

Baseline Characteristics

Arm/Group Title	PG324 Ophthalmic Solution	AR-13324 Ophthalmic Solution 0.02%	Latanoprost Ophthalmic Solution 0.005%	Total
Arm/Group Description	PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Netarsudil (AR-13324) Ophthalmic Solution 0.02%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Total of all reporting groups
Overall Participants	238	244	236	718
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	109 45.8%	107 43.9%	95 40.3%	311 43.3%
>=65 years	129 54.2%	137 56.1%	141 59.7%	407 56.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.4 (11.33)	64.6 (10.97)	65.4 (10.98)	64.8 (11.09)
Sex: Female, Male (Count of Participants)
Female	134 56.3%	136 55.7%	136 57.6%	406 56.5%
Male	104 43.7%	108 44.3%	100 42.4%	312 43.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	30 12.6%	32 13.1%	30 12.7%	92 12.8%
Not Hispanic or Latino	208 87.4%	212 86.9%	206 87.3%	626 87.2%
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%	0 0%	0 0%
Asian	7 2.9%	6 2.5%	10 4.2%	23 3.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	69 29%	70 28.7%	67 28.4%	206 28.7%
White	162 68.1%	167 68.4%	157 66.5%	486 67.7%
More than one race	0 0%	1 0.4%	2 0.8%	3 0.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Intraocular Pressure (IOP)
Description	The primary efficacy variable was mean IOP at 08:00, 10:00 and 16:00 hours at Day 15, Day 43 and Day 90, as measured by Goldmann applanation tonometry. Secondary analysis were conducted as a part of safety measurements to month 12 on treatment.
Time Frame	Primary efficacy endpoint measured for 3 months (data collected at 08:00, 10:00 and 16:00 hours at Day 15, Day 43 and Day 90)

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population

Arm/Group Title	PG324 Ophthalmic Solution	AR-13324 Ophthalmic Solution 0.02%	Latanoprost Ophthalmic Solution 0.005%
Arm/Group Description	PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Netarsudil (AR-13324) Ophthalmic Solution 0.02%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)
Measure Participants	238	244	236
Day 1, 0800 hours	24.84 (3.316)	24.81 (3.335)	24.59 (2.914)
Day 1, 1000 hours	23.72 (3.587)	23.45 (3.510)	23.43 (3.385)
Day 1, 1600 hours	22.59 (3.610)	22.63 (3.674)	23.43 (3.370)
Day 15, 0800 hours	15.68 (3.532)	18.66 (4.189)	17.74 (3.467)
Day 15, 1000 hours	14.93 (3.417)	17.78 (4.219)	17.36 (3.548)
Day 15, 1600 hours	14.83 (2.978)	17.25 (3.814)	17.11 (3.236)
Day 43, 0800 hours	16.04 (3.268)	19.06 (4.593)	17.58 (3.465)
Day 43, 1000 hours	15.39 (3.175)	17.92 (4.168)	17.06 (3.250)
Day 43, 1600 hours	15.43 (3.065)	17.54 (3.855)	16.97 (3.240)
Day 90, 0800 hours	16.37 (3.377)	19.04 (4.537)	17.53 (3.280)
Day 90, 1000 hours	15.41 (3.038)	17.96 (4.262)	16.88 (3.139)
Day 90, 1600 hours	15.49 (3.126)	17.30 (3.769)	16.67 (3.115)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PG324 Ophthalmic Solution, AR-13324 Ophthalmic Solution 0.02%
	Comments
	Type of Statistical Test	Superiority
	Comments	To claim superiority PG324 had to be statistically superior to netarsudil and to latanoprost at all 9 of 9 primary efficacy timepoints
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

2. Secondary Outcome

Title	Extent of Exposure
Description	Exposure to study medication in days for all treatment groups
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The safety population= all randomized subjects who received at least 1 dose of study medication. The safety population summarized subjects as-treated. 1 Subject was randomized to netarsudil but received latanoprost. Therefore, 1 less subject is in the netarsudil group and 1 additional subject is in the latanoprost group for the safety population.

Arm/Group Title	PG324 Ophthalmic Solution 0.02%/0.005%	AR-13324 Ophthalmic Solution 0.02%	Latanoprost Ophthalmic Solution 0.005%
Arm/Group Description	Fixed combination of netarsudil 0.02%, latanoprost 0.005% ophthalmic solution PG324 Ophthalmic Solution 0.02%/0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Netarsudil 0.02% ophthalmic solution Netarsudil (AR-13324) Ophthalmic Solution 0.02%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Latanoprost 0.005% ophthalmic solution Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)
Measure Participants	238	243	237
Mean (Standard Deviation) [days]	275.7 (129.94)	266.2 (131.60)	330.4 (89.60)

Adverse Events

Time Frame	Adverse event data was collected during the course of the study of 12 month treatment and 2 month safety follow up.The safety population summarized subjects as-treated.
Adverse Event Reporting Description	Safety population, defined as all randomized subjects who received at least 1 dose of investigational product.The safety population summarized subjects as-treated. 1 Subject was randomized to netarsudil but received latanoprost. Therefore, 1 less subject is in the netarsudil group and 1 additional subject is in the latanoprost group for the safety population. (applies to the numbers of subjects for SAEs, all cause mortality and other AEs sections)
Arm/Group Title	PG324 Ophthalmic Solution		AR-13324 Ophthalmic Solution 0.02%		Latanoprost Ophthalmic Solution 0.005%
Arm/Group Description	PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)		Netarsudil (AR-13324) Ophthalmic Solution 0.02%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)		Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)
All Cause Mortality
	PG324 Ophthalmic Solution		AR-13324 Ophthalmic Solution 0.02%		Latanoprost Ophthalmic Solution 0.005%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/238 (0%)		1/243 (0.4%)		0/237 (0%)
Serious Adverse Events
	PG324 Ophthalmic Solution		AR-13324 Ophthalmic Solution 0.02%		Latanoprost Ophthalmic Solution 0.005%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/238 (2.1%)		10/243 (4.1%)		10/237 (4.2%)
Blood and lymphatic system disorders
Anaemia	1/238 (0.4%)	1	0/243 (0%)	0	0/237 (0%)	0
Cardiac disorders
Myocardial Infarction	0/238 (0%)	0	0/243 (0%)	0	2/237 (0.8%)	2
Coronary Artery Stenosis	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Gastrointestinal disorders
Abdominal Pain	1/238 (0.4%)	1	0/243 (0%)	0	0/237 (0%)	0
Gastrointestinal Haemorrhage	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Impaired Gastric Emptying	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Lower Gastrointestinal Haemorrhage	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Hepatobiliary disorders
Cholecystitis	1/238 (0.4%)	1	0/243 (0%)	0	0/237 (0%)	0
Infections and infestations
Cellulitis	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Pneumonia	1/238 (0.4%)	1	0/243 (0%)	0	0/237 (0%)	0
Sepsis	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Injury, poisoning and procedural complications
Fall	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Femoral Neck Fracture	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Metabolism and nutrition disorders
Hypoglycaemia	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Cancer	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Breast Cancer	1/238 (0.4%)	1	0/243 (0%)	0	0/237 (0%)	0
Gastric Cancer Recurrent	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Intraductal Proliferative Breast Lesion	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Ovarian Adenoma	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Prostate Cancer Recurrent	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Nervous system disorders
Carotid Artery Stenosis	1/238 (0.4%)	1	0/243 (0%)	0	0/237 (0%)	0
Metabolic Encephalopathy	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Syncope	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchitis Chronic	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Pulmonary Embolism	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Vascular disorders
Arteriosclerosis	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Deep Vein Thrombosis	0/238 (0%)	0	0/243 (0%)	0	1/237 (0.4%)	1
Hypertension	0/238 (0%)	0	1/243 (0.4%)	1	0/237 (0%)	0
Other (Not Including Serious) Adverse Events
	PG324 Ophthalmic Solution		AR-13324 Ophthalmic Solution 0.02%		Latanoprost Ophthalmic Solution 0.005%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	169/238 (71%)		160/243 (65.8%)		74/237 (31.2%)
Eye disorders
Conjunctival Hyperaemia	133/238 (55.9%)	133	115/243 (47.3%)	115	44/237 (18.6%)	44
Cornea Verticillata	39/238 (16.4%)	39	32/243 (13.2%)	32	0/237 (0%)	0
Eye Pruritus	20/238 (8.4%)	20	20/243 (8.2%)	20	2/237 (0.8%)	2
Lacrimation Increased	15/238 (6.3%)	15	17/243 (7%)	17	1/237 (0.4%)	1
Conjunctival Haemorrhage	10/238 (4.2%)	10	14/243 (5.8%)	14	2/237 (0.8%)	2
Punctate Keratitis	9/238 (3.8%)	9	13/243 (5.3%)	13	4/237 (1.7%)	4
Vision Blurred	9/238 (3.8%)	9	14/243 (5.8%)	14	3/237 (1.3%)	3
General disorders
Instillation Site Pain	52/238 (21.8%)	52	55/243 (22.6%)	55	18/237 (7.6%)	18

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.