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 0.02% and latanoprost ophthalmic solution 0.005%
Interventions
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)
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 99 Years
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: 12. Clinically significant abnormalities in lab tests at screening 13. Clinically significant systemic disease 14. Participation in any investigational study within 60 days prior to screening 15. 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 16. Women of childbearing potential who were 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) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PG324 Ophthalmic Solution 1 drop daily in the evening (PM) in both eyes (OU) | 245 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% 1 drop daily in the evening (PM) in both eyes (OU) | 255 |
| Latanoprost Ophthalmic Solution 0.005% 1 drop daily in the evening (PM) in both eyes (OU) | 250 |
| Total | 750 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 17 | 15 | 5 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Disallowed Concurrent Medication | 2 | 2 | 0 |
| Overall Study | Lack of Efficacy | 0 | 3 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 2 |
| Overall Study | No-compliant subject | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 2 |
| Overall Study | Subject missed V6.2 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 5 | 4 |
Baseline characteristics
| Characteristic | PG324 Ophthalmic Solution | Netarsudil (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 | 127 Participants | 146 Participants | 138 Participants | 411 Participants |
| Age, Categorical Between 18 and 65 years | 118 Participants | 109 Participants | 112 Participants | 339 Participants |
| Age, Continuous | 64.2 years STANDARD_DEVIATION 11.81 | 64.5 years STANDARD_DEVIATION 10.58 | 64.3 years STANDARD_DEVIATION 11.41 | 64.3 years STANDARD_DEVIATION 11.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 48 Participants | 55 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 200 Participants | 207 Participants | 195 Participants | 602 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 11 Participants | 6 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 74 Participants | 76 Participants | 79 Participants | 229 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 0 Participants | 5 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 | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 161 Participants | 165 Participants | 163 Participants | 489 Participants |
| Sex: Female, Male Female | 152 Participants | 153 Participants | 144 Participants | 449 Participants |
| Sex: Female, Male Male | 93 Participants | 102 Participants | 106 Participants | 301 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 244 | 1 / 255 | 0 / 251 |
| other Total, other adverse events | 157 / 244 | 143 / 255 | 78 / 251 |
| serious Total, serious adverse events | 2 / 244 | 6 / 255 | 5 / 251 |
Outcome results
Primary
Intraocular Pressure (IOP)
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
Population: Intent to treat (ITT) population with Monte Carlo Markov Chain (MCMC) imputation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 1, 0800 hours | 24.69 mmHg | Standard Deviation 3.422 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 1, 1000 hours | 23.33 mmHg | Standard Deviation 3.399 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 1, 1600 hours | 22.37 mmHg | Standard Deviation 3.492 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 15, 0800 hours | 16.06 mmHg | Standard Deviation 3.37 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 15, 1000 hours | 15.31 mmHg | Standard Deviation 3.272 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 15, 1600 hours | 15.16 mmHg | Standard Deviation 3.032 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 43, 0800 hours | 16.43 mmHg | Standard Deviation 3.717 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 43, 1000 hours | 15.54 mmHg | Standard Deviation 3.533 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 43, 1600 hours | 15.45 mmHg | Standard Deviation 3.525 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 90, 0800 hours | 16.45 mmHg | Standard Deviation 3.572 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 90, 1000 hours | 15.58 mmHg | Standard Deviation 3.307 |
| PG324 Ophthalmic Solution | Intraocular Pressure (IOP) | Day 90, 1600 hours | 15.52 mmHg | Standard Deviation 3.21 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 90, 1600 hours | 17.94 mmHg | Standard Deviation 3.627 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 1, 0800 hours | 24.66 mmHg | Standard Deviation 3.148 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 43, 0800 hours | 19.52 mmHg | Standard Deviation 4.273 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 43, 1600 hours | 17.95 mmHg | Standard Deviation 3.776 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 1, 1000 hours | 23.40 mmHg | Standard Deviation 3.538 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 15, 1600 hours | 17.53 mmHg | Standard Deviation 3.772 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 90, 1000 hours | 18.30 mmHg | Standard Deviation 3.846 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 1, 1600 hours | 22.76 mmHg | Standard Deviation 3.558 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 43, 1000 hours | 18.40 mmHg | Standard Deviation 3.81 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 15, 1000 hours | 17.99 mmHg | Standard Deviation 3.909 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 15, 0800 hours | 19.35 mmHg | Standard Deviation 4.279 |
| Netarsudil (AR-13324) Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 90, 0800 hours | 19.72 mmHg | Standard Deviation 4.419 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 15, 0800 hours | 18.10 mmHg | Standard Deviation 3.375 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 15, 1000 hours | 17.61 mmHg | Standard Deviation 3.264 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 90, 0800 hours | 17.98 mmHg | Standard Deviation 3.4 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 15, 1600 hours | 17.08 mmHg | Standard Deviation 3.283 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 43, 0800 hours | 17.93 mmHg | Standard Deviation 3.586 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 43, 1000 hours | 17.35 mmHg | Standard Deviation 3.224 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 90, 1000 hours | 17.48 mmHg | Standard Deviation 3.366 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 1, 0800 hours | 24.75 mmHg | Standard Deviation 3.24 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 1, 1000 hours | 23.23 mmHg | Standard Deviation 3.339 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 43, 1600 hours | 17.09 mmHg | Standard Deviation 3.271 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 1, 1600 hours | 22.59 mmHg | Standard Deviation 3.451 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 90, 1600 hours | 17.14 mmHg | Standard Deviation 3.044 |
p-value: <0.0001t-test, 2 sided
p-value: <0.0001t-test, 2 sided