Trial Outcomes & Findings for Double-masked Study of PG324 Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension (NCT NCT02558400)

Last Updated: 2019-06-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

718 participants

Primary outcome timeframe

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)

Results posted on

2019-06-04

Participant Flow

Participant milestones

Participant milestones
Measure	PG324 Ophthalmic Solution 0.02%/0.005% PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	AR-13324 Ophthalmic Solution 0.02% 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% Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)
Overall Study STARTED	238	244	236
Overall Study COMPLETED	159	148	203
Overall Study NOT COMPLETED	79	96	33

Reasons for withdrawal

Reasons for withdrawal
Measure	PG324 Ophthalmic Solution 0.02%/0.005% PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	AR-13324 Ophthalmic Solution 0.02% 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% Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)
Overall Study Adverse Event	47	53	4
Overall Study Withdrawal by Subject	13	9	8
Overall Study Non-Compliant	0	1	3
Overall Study Lost to Follow-up	5	5	4
Overall Study Lack of Efficacy	0	13	1
Overall Study Disallowed Concurrent Medication	6	7	5
Overall Study Physician Decision	2	2	0
Overall Study Protocol Violation	6	3	8
Overall Study Death	0	1	0
Overall Study Ineligible for the study	0	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PG324 Ophthalmic Solution n=238 Participants PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	AR-13324 Ophthalmic Solution 0.02% n=244 Participants 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% n=236 Participants Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	Total n=718 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	109 Participants n=5 Participants	107 Participants n=7 Participants	95 Participants n=5 Participants	311 Participants n=4 Participants
Age, Categorical >=65 years	129 Participants n=5 Participants	137 Participants n=7 Participants	141 Participants n=5 Participants	407 Participants n=4 Participants
Age, Continuous	64.4 years STANDARD_DEVIATION 11.33 • n=5 Participants	64.6 years STANDARD_DEVIATION 10.97 • n=7 Participants	65.4 years STANDARD_DEVIATION 10.98 • n=5 Participants	64.8 years STANDARD_DEVIATION 11.09 • n=4 Participants
Sex: Female, Male Female	134 Participants n=5 Participants	136 Participants n=7 Participants	136 Participants n=5 Participants	406 Participants n=4 Participants
Sex: Female, Male Male	104 Participants n=5 Participants	108 Participants n=7 Participants	100 Participants n=5 Participants	312 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	30 Participants n=5 Participants	32 Participants n=7 Participants	30 Participants n=5 Participants	92 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	208 Participants n=5 Participants	212 Participants n=7 Participants	206 Participants n=5 Participants	626 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	23 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	69 Participants n=5 Participants	70 Participants n=7 Participants	67 Participants n=5 Participants	206 Participants n=4 Participants
Race (NIH/OMB) White	162 Participants n=5 Participants	167 Participants n=7 Participants	157 Participants n=5 Participants	486 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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)

Population: Intent to Treat (ITT) population

Outcome measures

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

SECONDARY outcome

Timeframe: 12 months

Population: 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.

Exposure to study medication in days for all treatment groups

Outcome measures

Outcome measures
Measure	PG324 Ophthalmic Solution n=238 Participants PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	AR-13324 Ophthalmic Solution 0.02% n=243 Participants 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% n=237 Participants Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)
Extent of Exposure	275.7 days Standard Deviation 129.94	266.2 days Standard Deviation 131.60	330.4 days Standard Deviation 89.60

Adverse Events

PG324 Ophthalmic Solution

Serious events: 5 serious events

Other events: 169 other events

Deaths: 0 deaths

AR-13324 Ophthalmic Solution 0.02%

Serious events: 10 serious events

Other events: 160 other events

Deaths: 1 deaths

Latanoprost Ophthalmic Solution 0.005%

Serious events: 10 serious events

Other events: 74 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	PG324 Ophthalmic Solution n=238 participants at risk PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)	AR-13324 Ophthalmic Solution 0.02% n=243 participants at risk 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% n=237 participants at risk Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU)
Eye disorders Conjunctival Hyperaemia	55.9% 133/238 • Number of events 133 • 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. 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)	47.3% 115/243 • Number of events 115 • 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. 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)	18.6% 44/237 • Number of events 44 • 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. 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)
Eye disorders Cornea Verticillata	16.4% 39/238 • Number of events 39 • 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. 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)	13.2% 32/243 • Number of events 32 • 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. 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)	0.00% 0/237 • 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. 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)
Eye disorders Eye Pruritus	8.4% 20/238 • Number of events 20 • 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. 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)	8.2% 20/243 • Number of events 20 • 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. 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)	0.84% 2/237 • Number of events 2 • 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. 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)
Eye disorders Lacrimation Increased	6.3% 15/238 • Number of events 15 • 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. 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)	7.0% 17/243 • Number of events 17 • 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. 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)	0.42% 1/237 • Number of events 1 • 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. 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)
Eye disorders Conjunctival Haemorrhage	4.2% 10/238 • Number of events 10 • 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. 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)	5.8% 14/243 • Number of events 14 • 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. 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)	0.84% 2/237 • Number of events 2 • 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. 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)
Eye disorders Punctate Keratitis	3.8% 9/238 • Number of events 9 • 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. 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)	5.3% 13/243 • Number of events 13 • 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. 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)	1.7% 4/237 • Number of events 4 • 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. 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)
Eye disorders Vision Blurred	3.8% 9/238 • Number of events 9 • 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. 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)	5.8% 14/243 • Number of events 14 • 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. 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)	1.3% 3/237 • Number of events 3 • 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. 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)
General disorders Instillation Site Pain	21.8% 52/238 • Number of events 52 • 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. 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)	22.6% 55/243 • Number of events 55 • 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. 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)	7.6% 18/237 • Number of events 18 • 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. 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)

Additional Information

Theresa GH Heah, MD, MBA

Aerie Pharmaceuticals, Inc

Phone: 908-947-3844

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place