Open-angle Glaucoma, Ocular Hypertension
Conditions
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.
Interventions
1 drop once daily (QD), in the evening (PM) in both eyes (OU)
1 drop once daily (QD), in the evening (PM) in both eyes (OU)
1 drop once daily (QD), in the evening (PM) in both eyes (OU)
Sponsors
Aerie Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Extent of Exposure | 12 months | Exposure to study medication in days for all treatment groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PG324 Ophthalmic Solution PG324 Ophthalmic Solution: 1 drop once daily (QD), in the evening (PM) in both eyes (OU) | 238 |
| 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) | 244 |
| Latanoprost Ophthalmic Solution 0.005% Latanoprost Ophthalmic Solution 0.005%: 1 drop once daily (QD), in the evening (PM) in both eyes (OU) | 236 |
| Total | 718 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 47 | 53 | 4 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Disallowed Concurrent Medication | 6 | 7 | 5 |
| Overall Study | Ineligible for the study | 0 | 2 | 0 |
| Overall Study | Lack of Efficacy | 0 | 13 | 1 |
| Overall Study | Lost to Follow-up | 5 | 5 | 4 |
| Overall Study | Non-Compliant | 0 | 1 | 3 |
| Overall Study | Physician Decision | 2 | 2 | 0 |
| Overall Study | Protocol Violation | 6 | 3 | 8 |
| Overall Study | Withdrawal by Subject | 13 | 9 | 8 |
Baseline characteristics
| Characteristic | PG324 Ophthalmic Solution | AR-13324 Ophthalmic Solution 0.02% | Latanoprost Ophthalmic Solution 0.005% | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 129 Participants | 137 Participants | 141 Participants | 407 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants | 107 Participants | 95 Participants | 311 Participants |
| Age, Continuous | 64.4 years STANDARD_DEVIATION 11.33 | 64.6 years STANDARD_DEVIATION 10.97 | 65.4 years STANDARD_DEVIATION 10.98 | 64.8 years STANDARD_DEVIATION 11.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants | 32 Participants | 30 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 208 Participants | 212 Participants | 206 Participants | 626 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 6 Participants | 10 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 69 Participants | 70 Participants | 67 Participants | 206 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 162 Participants | 167 Participants | 157 Participants | 486 Participants |
| Sex: Female, Male Female | 134 Participants | 136 Participants | 136 Participants | 406 Participants |
| Sex: Female, Male Male | 104 Participants | 108 Participants | 100 Participants | 312 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 238 | 1 / 243 | 0 / 237 |
| other Total, other adverse events | 169 / 238 | 160 / 243 | 74 / 237 |
| serious Total, serious adverse events | 5 / 238 | 10 / 243 | 10 / 237 |
Outcome results
Primary
Intraocular Pressure (IOP)
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)
Population: Intent to Treat (ITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 1, 0800 hours | 24.84 mmHg | Standard Deviation 3.316 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 1, 1000 hours | 23.72 mmHg | Standard Deviation 3.587 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 1, 1600 hours | 22.59 mmHg | Standard Deviation 3.61 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 15, 0800 hours | 15.68 mmHg | Standard Deviation 3.532 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 15, 1000 hours | 14.93 mmHg | Standard Deviation 3.417 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 15, 1600 hours | 14.83 mmHg | Standard Deviation 2.978 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 43, 0800 hours | 16.04 mmHg | Standard Deviation 3.268 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 43, 1000 hours | 15.39 mmHg | Standard Deviation 3.175 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 43, 1600 hours | 15.43 mmHg | Standard Deviation 3.065 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 90, 0800 hours | 16.37 mmHg | Standard Deviation 3.377 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 90, 1000 hours | 15.41 mmHg | Standard Deviation 3.038 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 90, 1600 hours | 15.49 mmHg | Standard Deviation 3.126 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 90, 1600 hours | 17.30 mmHg | Standard Deviation 3.769 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 1, 0800 hours | 24.81 mmHg | Standard Deviation 3.335 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 43, 0800 hours | 19.06 mmHg | Standard Deviation 4.593 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 43, 1600 hours | 17.54 mmHg | Standard Deviation 3.855 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 1, 1000 hours | 23.45 mmHg | Standard Deviation 3.51 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 15, 1600 hours | 17.25 mmHg | Standard Deviation 3.814 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 90, 1000 hours | 17.96 mmHg | Standard Deviation 4.262 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 1, 1600 hours | 22.63 mmHg | Standard Deviation 3.674 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 43, 1000 hours | 17.92 mmHg | Standard Deviation 4.168 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 15, 1000 hours | 17.78 mmHg | Standard Deviation 4.219 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 15, 0800 hours | 18.66 mmHg | Standard Deviation 4.189 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 90, 0800 hours | 19.04 mmHg | Standard Deviation 4.537 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 15, 0800 hours | 17.74 mmHg | Standard Deviation 3.467 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 15, 1000 hours | 17.36 mmHg | Standard Deviation 3.548 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 90, 0800 hours | 17.53 mmHg | Standard Deviation 3.28 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 15, 1600 hours | 17.11 mmHg | Standard Deviation 3.236 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 43, 0800 hours | 17.58 mmHg | Standard Deviation 3.465 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 43, 1000 hours | 17.06 mmHg | Standard Deviation 3.25 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 90, 1000 hours | 16.88 mmHg | Standard Deviation 3.139 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 1, 0800 hours | 24.59 mmHg | Standard Deviation 2.914 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 1, 1000 hours | 23.43 mmHg | Standard Deviation 3.385 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 43, 1600 hours | 16.97 mmHg | Standard Deviation 3.24 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 1, 1600 hours | 23.43 mmHg | Standard Deviation 3.37 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 90, 1600 hours | 16.67 mmHg | Standard Deviation 3.115 |
p-value: <0.0001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
Secondary
Extent of Exposure
Exposure to study medication in days for all treatment groups
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PG324 Ophthalmic Solution | Extent of Exposure | 275.7 days | Standard Deviation 129.94 |
| AR-13324 Ophthalmic Solution 0.02% | Extent of Exposure | 266.2 days | Standard Deviation 131.6 |
| Latanoprost Ophthalmic Solution 0.005% | Extent of Exposure | 330.4 days | Standard Deviation 89.6 |