Open-angle Glaucoma, Ocular Hypertension
Conditions
Brief summary
To evaluate ocular hypotensive efficacy and safety of Netarsudil (AR-13324) Ophthalmic Solution compared to Timolol Maleate Ophthalmic Solution.
Interventions
1 drop once daily (QD), PM, OU
1 drop BID, AM/PM, OU
OTHERPlacebo
1 drop QD, AM, OU
Sponsors
Aerie Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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. Post-washout intraocular pressure \>20mmHg and \<30mmHg in 1 or both eyes at 2 qualification visits 4. Corrected visual acuity equivalent to 20/200 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 ≥30mmHg 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. Known hypersensitivity or contraindication to beta-adrenoceptor antagonists 15. Clinically significant systemic disease 16. Participation in any investigational study within 60 days prior to screening 17. Used any systemic medication that could have a substantial effect in intraocular pressure within 30 days prior to screening 18. 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 |
|---|---|---|
| IOP (Intraocular Pressure) | 3 months | The primary efficacy outcome is mean IOP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Exposure | 6 months | Exposure to study medication in days for all treatment groups |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 53 sites starting in September 2015
Participants by arm
| Arm | Count |
|---|---|
| AR-13324 Ophthalmic Solution 0.02% & Placebo 1 drop AR-13324 in the evening (PM) and 1 drop placebo in the morning (AM) in both eyes (OU) | 351 |
| Timolol Maleate Ophthalmic Solution 0.5% BID 1 drop twice daily (BID) in the morning (AM) and evening (PM) in both eyes (OU) | 357 |
| Total | 708 |
Baseline characteristics
| Characteristic | Timolol Maleate Ophthalmic Solution 0.5% BID | Total | AR-13324 Ophthalmic Solution 0.02% & Placebo |
|---|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 10.97 | 64.3 years STANDARD_DEVIATION 11.25 | 64.1 years STANDARD_DEVIATION 11.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 87 Participants | 176 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 270 Participants | 532 Participants | 262 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 13 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 75 Participants | 159 Participants | 84 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 274 Participants | 533 Participants | 259 Participants |
| Sex: Female, Male Female | 237 Participants | 445 Participants | 208 Participants |
| Sex: Female, Male Male | 120 Participants | 263 Participants | 143 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 351 | 0 / 357 |
| other Total, other adverse events | 245 / 351 | 139 / 357 |
| serious Total, serious adverse events | 8 / 351 | 10 / 357 |
Outcome results
Primary
IOP (Intraocular Pressure)
The primary efficacy outcome is mean IOP
Time frame: 3 months
Population: Per-Protocol Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 1, 0800 hours | 23.93 mmHg | Standard Deviation 2.441 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 1, 1000 hours | 22.67 mmHg | Standard Deviation 2.826 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 1, 1600 hours | 22.17 mmHg | Standard Deviation 2.857 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 15, 0800 hours | 19.20 mmHg | Standard Deviation 3.833 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 15, 1000 hours | 17.93 mmHg | Standard Deviation 3.678 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 15, 1600 hours | 17.76 mmHg | Standard Deviation 3.527 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 43, 0800 hours | 19.45 mmHg | Standard Deviation 3.929 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 43, 1000 hours | 18.12 mmHg | Standard Deviation 3.56 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 43, 1600 hours | 17.89 mmHg | Standard Deviation 3.438 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 90, 0800 hours | 19.24 mmHg | Standard Deviation 3.889 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 90, 1000 hours | 18.30 mmHg | Standard Deviation 3.637 |
| AR-13324 Ophthalmic Solution 0.02% & Placebo | IOP (Intraocular Pressure) | Day 90, 1600 hours | 18.02 mmHg | Standard Deviation 3.644 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 90, 1000 hours | 17.60 mmHg | Standard Deviation 3.173 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 1, 0800 hours | 23.89 mmHg | Standard Deviation 2.318 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 43, 0800 hours | 18.52 mmHg | Standard Deviation 3.316 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 1, 1000 hours | 22.77 mmHg | Standard Deviation 2.565 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 90, 0800 hours | 18.35 mmHg | Standard Deviation 3.196 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 1, 1600 hours | 22.04 mmHg | Standard Deviation 2.708 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 43, 1000 hours | 17.89 mmHg | Standard Deviation 3.157 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 15, 0800 hours | 18.60 mmHg | Standard Deviation 3.396 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 90, 1600 hours | 17.66 mmHg | Standard Deviation 3.08 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 15, 1000 hours | 17.80 mmHg | Standard Deviation 3.237 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 43, 1600 hours | 17.88 mmHg | Standard Deviation 3.356 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | IOP (Intraocular Pressure) | Day 15, 1600 hours | 17.85 mmHg | Standard Deviation 3.102 |
Secondary
Extent of Exposure
Exposure to study medication in days for all treatment groups
Time frame: 6 months
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AR-13324 Ophthalmic Solution 0.02% & Placebo | Extent of Exposure | 147.4 days | Standard Deviation 54.47 |
| Timolol Maleate Ophthalmic Solution 0.5% BID | Extent of Exposure | 167.7 days | Standard Deviation 36.4 |