Trial Outcomes & Findings for Safety and Efficacy Study of PG324 (Netarsudil/Latanoprost 0.02% / 0.005%) Ophthalmic Solution Compared to GANFORT® Ophthalmic Solution in Open Angle Glaucoma or Ocular Hypertension (NCT NCT03284853)

NCT ID: NCT03284853

Last Updated: 2022-01-31

Results Overview

Comparison of PG324 to Ganfort for mean intraocular pressure at specified timepoints at Week 2, Week 6 and Month 3.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

436 participants

Primary outcome timeframe

Day 90

Results posted on

2022-01-31

Participant Flow

Recruitment took place in 11 European countries between September 2017 and May 2020.

All participants underwent a period of washout for their pre-study ocular hypotensive medication for a prescribed period (up to 4 weeks or longer), depending on the medication, before receiving study medication. From the total 436 participants, 6 were not included in the analysis due to serious GCP breaches (2 from the Netarsudil/Latanoprost 0.02%/0.005% arm and 4 from the Ganfort arm). The remaining 430 participants (218 and 212 respectively) were included in the analysis.

Participant milestones

Participant milestones
Measure	Netarsudil/Latanoprost 0.02%/0.005% PG324 Ophthalmic Solution (netarsudil 0.02% / latanoprost 0.005%) one drop daily to each eye for 180 days. Netarsudil/Latanoprost 0.02%/0.005%: Topical sterile ophthalmic solution	GANFORT® GANFORT® (bimatoprost 0.03%/timolol 0.5%) Ophthalmic solution one drop daily to each eye for 180 days. GANFORT®: Topical sterile ophthalmic solution
Overall Study STARTED	218	212
Overall Study Intent-to-Treat Population	218	212
Overall Study Per-Protocol Population	169	170
Overall Study Safety Population	218	212
Overall Study COMPLETED	163	199
Overall Study NOT COMPLETED	55	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Netarsudil/Latanoprost 0.02%/0.005% PG324 Ophthalmic Solution (netarsudil 0.02% / latanoprost 0.005%) one drop daily to each eye for 180 days. Netarsudil/Latanoprost 0.02%/0.005%: Topical sterile ophthalmic solution	GANFORT® GANFORT® (bimatoprost 0.03%/timolol 0.5%) Ophthalmic solution one drop daily to each eye for 180 days. GANFORT®: Topical sterile ophthalmic solution
Overall Study Adverse Event	40	4
Overall Study Withdrawal by Subject	5	1
Overall Study Lost to Follow-up	1	0
Overall Study Lack of Efficacy	1	0
Overall Study Disallowed Concurrent Medication	1	1
Overall Study Protocol Violation	3	3
Overall Study Death	0	1
Overall Study Other - Reason not reported in CSR	4	3

Baseline Characteristics

Safety and Efficacy Study of PG324 (Netarsudil/Latanoprost 0.02% / 0.005%) Ophthalmic Solution Compared to GANFORT® Ophthalmic Solution in Open Angle Glaucoma or Ocular Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Netarsudil/Latanoprost 0.02%/0.005% n=218 Participants PG324 Ophthalmic Solution (netarsudil 0.02% / latanoprost 0.005%) one drop daily to each eye for 180 days. Netarsudil/Latanoprost 0.02%/0.005%: Topical sterile ophthalmic solution	GANFORT® n=212 Participants GANFORT® (bimatoprost 0.03%/timolol 0.5%) Ophthalmic solution one drop daily to each eye for 180 days. GANFORT®: Topical sterile ophthalmic solution	Total n=430 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	71 Participants n=99 Participants	79 Participants n=107 Participants	150 Participants n=206 Participants
Age, Categorical >=65 years	147 Participants n=99 Participants	133 Participants n=107 Participants	280 Participants n=206 Participants
Age, Continuous Mean	67.3 years n=99 Participants	67.0 years n=107 Participants	67.2 years n=206 Participants
Sex: Female, Male Female	131 Participants n=99 Participants	92 Participants n=107 Participants	223 Participants n=206 Participants
Sex: Female, Male Male	87 Participants n=99 Participants	120 Participants n=107 Participants	207 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	61 Participants n=99 Participants	56 Participants n=107 Participants	117 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	157 Participants n=99 Participants	156 Participants n=107 Participants	313 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	4 Participants n=99 Participants	5 Participants n=107 Participants	9 Participants n=206 Participants
Race (NIH/OMB) White	210 Participants n=99 Participants	200 Participants n=107 Participants	410 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=99 Participants	4 Participants n=107 Participants	8 Participants n=206 Participants
Region of Enrollment Austria	17 participants n=99 Participants	17 participants n=107 Participants	34 participants n=206 Participants
Region of Enrollment Latvia	8 participants n=99 Participants	8 participants n=107 Participants	16 participants n=206 Participants
Region of Enrollment Belgium	5 participants n=99 Participants	5 participants n=107 Participants	10 participants n=206 Participants
Region of Enrollment Hungary	8 participants n=99 Participants	11 participants n=107 Participants	19 participants n=206 Participants
Region of Enrollment Czechia	30 participants n=99 Participants	31 participants n=107 Participants	61 participants n=206 Participants
Region of Enrollment Poland	3 participants n=99 Participants	3 participants n=107 Participants	6 participants n=206 Participants
Region of Enrollment Italy	21 participants n=99 Participants	21 participants n=107 Participants	42 participants n=206 Participants
Region of Enrollment United Kingdom	20 participants n=99 Participants	15 participants n=107 Participants	35 participants n=206 Participants
Region of Enrollment France	2 participants n=99 Participants	4 participants n=107 Participants	6 participants n=206 Participants
Region of Enrollment Germany	38 participants n=99 Participants	36 participants n=107 Participants	74 participants n=206 Participants
Region of Enrollment Spain	66 participants n=99 Participants	61 participants n=107 Participants	127 participants n=206 Participants

PRIMARY outcome

Timeframe: Day 90

Population: A total of 430 (100%) participants were included in the Safety and Intent-to-Treat populations.

Comparison of PG324 to Ganfort for mean intraocular pressure at specified timepoints at Week 2, Week 6 and Month 3.

Outcome measures

Outcome measures
Measure	Netarsudil/Latanoprost 0.02%/0.005% n=218 Participants PG324 Ophthalmic Solution (netarsudil 0.02% / latanoprost 0.005%) one drop daily to each eye for 180 days. Netarsudil/Latanoprost 0.02%/0.005%: Topical sterile ophthalmic solution	GANFORT® n=212 Participants GANFORT® (bimatoprost 0.03%/timolol 0.5%) Ophthalmic solution one drop daily to each eye for 180 days. GANFORT®: Topical sterile ophthalmic solution
Mean Diurnal Intraocular Pressure by Goldmann Applanation Tonometry Month 3	15.61 mmHg Interval 15.28 to 15.93	15.19 mmHg Interval 15.09 to 15.27
Mean Diurnal Intraocular Pressure by Goldmann Applanation Tonometry Week 2	15.39 mmHg Interval 15.09 to 15.84	15.56 mmHg Interval 15.42 to 15.67
Mean Diurnal Intraocular Pressure by Goldmann Applanation Tonometry Week 6	15.64 mmHg Interval 15.18 to 16.2	15.25 mmHg Interval 15.16 to 15.32

Adverse Events

Netarsudil/Latanoprost 0.02%/0.005%

Serious events: 7 serious events

Other events: 117 other events

Deaths: 0 deaths

GANFORT®

Serious events: 7 serious events

Other events: 53 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Netarsudil/Latanoprost 0.02%/0.005% n=218 participants at risk PG324 Ophthalmic Solution (netarsudil 0.02% / latanoprost 0.005%) one drop daily to each eye for 180 days. Netarsudil/Latanoprost 0.02%/0.005%: Topical sterile ophthalmic solution	GANFORT® n=212 participants at risk GANFORT® (bimatoprost 0.03%/timolol 0.5%) Ophthalmic solution one drop daily to each eye for 180 days. GANFORT®: Topical sterile ophthalmic solution
Eye disorders Conjunctival Hyperemia	33.0% 72/218 • Number of events 72 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	10.8% 23/212 • Number of events 23 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Eye disorders Cornea Verticillata	11.0% 24/218 • Number of events 24 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.00% 0/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Eye disorders Conjunctival Hemorrhage	8.3% 18/218 • Number of events 18 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	2.4% 5/212 • Number of events 5 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Eye disorders Eye Pruritus	7.8% 17/218 • Number of events 17 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	1.9% 4/212 • Number of events 4 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Eye disorders Punctate Keratitis	5.5% 12/218 • Number of events 12 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	2.4% 5/212 • Number of events 5 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Eye disorders Conjunctivitis Allergic	5.5% 12/218 • Number of events 12 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Number of events 1 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Infections and infestations Viral Upper Respiratory Tract Infection	5.0% 11/218 • Number of events 11 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	4.7% 10/212 • Number of events 10 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Vascular disorders Hypertension	4.6% 10/218 • Number of events 10 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	8.0% 17/212 • Number of events 17 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.

Additional Information

Michelle Senchyna, PhD. Vice President, Clinical Development & Medical Affairs.

Aerie Pharmaceuticals Inc.

Phone: +1 908 947 3551

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Netarsudil/Latanoprost 0.02%/0.005% n=218 participants at risk PG324 Ophthalmic Solution (netarsudil 0.02% / latanoprost 0.005%) one drop daily to each eye for 180 days. Netarsudil/Latanoprost 0.02%/0.005%: Topical sterile ophthalmic solution	GANFORT® n=212 participants at risk GANFORT® (bimatoprost 0.03%/timolol 0.5%) Ophthalmic solution one drop daily to each eye for 180 days. GANFORT®: Topical sterile ophthalmic solution
Hepatobiliary disorders Cholecystitis	0.92% 2/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.00% 0/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Hepatobiliary disorders Cholecystitis acute	0.46% 1/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.00% 0/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Gastrointestinal disorders Enteritis	0.46% 1/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.00% 0/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Gastrointestinal disorders Pancreatitis	0.46% 1/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.00% 0/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Injury, poisoning and procedural complications Accidental poisoning	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.46% 1/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.00% 0/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Nervous system disorders Facial paralysis	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Nervous system disorders Ischemic stroke	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Cardiac disorders Cardiac failure	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Congenital, familial and genetic disorders Dermoid cyst	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.46% 1/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.00% 0/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Infections and infestations Lower respiratory tract infection	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Infections and infestations Pneumonia	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Renal and urinary disorders Renal failure	0.00% 0/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.47% 1/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.
Surgical and medical procedures Umbilical hernia repair	0.46% 1/218 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.	0.00% 0/212 • Adverse events were documented for each participant from the time of signing consent until 30 days after the last dose of Investigational Product. This was a maximum period of approximately 9 months (38 weeks) for participants who completed the full study duration.