Primary Open Angle Glaucoma or Ocular Hypertension
Conditions
Keywords
Aqueous Humor Dynamics, Trabecular Outflow, Netarsudil
Brief summary
To evaluate the effect on trabecular outflow facility of Netarsudil ophthalmic solution 0.02% compared to placebo
Detailed description
Trabecular outflow facility is a measure of aqueous humor dynamics; effect of netarsudil on this parameter as well as on intraocular pressure and episcleral venous pressure was evaluated in this study. Netarsudil treatment was given in one eye and placebo given in contralateral eye for 7 consecutive days.
Interventions
1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and Placebo comparator to the contralateral eye
OTHERPlacebo Comparator
1 drop daily (QD), in the morning (AM) of Placebo comparator administered to one eye and Netarsudil Ophthalmic Solution 0.02% to the contralateral eye
Sponsors
Aerie Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Paired comparison study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must be 18 years of age or older 2. Diagnosis of open primary angle glaucoma(POAG) or ocular hypertension (OHT) in both eyes 3. Unmedicated intraocular pressure (IOP) \>20 mmHg and \< 30 mmHg in both eyes at first qualification visit 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 glaucoma, or narrow angles 3. Intraocular pressure ≥30 mmHg in either eye 4. A difference in IOP between eyes \>4mmHg at qualification visit 5. Use of more than two ocular hypotensive medications within 30 days of screening 6. Known hypersensitivity to any component of the formulation 7. Previous glaucoma surgery or refractive surgery 8. Keratorefractive surgery in either eye 9. Report of ocular injury in either eye within the six months prior to screening or ocular or non-refractive surgery within 3 months prior to screening 10. Recent or current ocular infection or inflammation in either eye 11. Use of ocular medication in either eye of any kind within 30 days of screening 12. Mean central corneal thickness greater than 620 μm in either eye 13. Any abnormality preventing reliable applanation tonometry of either eye 14. Lack of suitable episcleral vein prior to performing Episcleral Venus Pressure (EVP) measurement (applicable to 1 site only) Systemic: 15. Clinically significant abnormalities within 6 weeks prior to screening 16. Clinically significant systemic disease 17. Participation in any investigational study within 60 days prior to screening 18. Use of systemic medication that could have an effect on intraocular pressure within 30 days prior to screening 19. 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 |
|---|---|---|
| Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility | Study treatment was administered for 7 days, and outcome measures collected on Day 8 | Mean diurnal change from baseline in trabecular (tonographic) outflow facility. |
| Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility. | Study treatment was administered for 7 days, and outcome measures collected on Day 8 | Mean diurnal change from baseline in trabecular (tonographic) outflow facility. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Study treatment was administered for 7 days, and outcome measures collected on Day 8 | Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants) |
| Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Study treatment was administered for 7 days, and outcome measures collected on Day 8 | Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Patients 1 drop daily (QD), in the morning (AM) Netarsudil Ophthalmic Solution 0.02% administered to one eye and placebo comparator to the contralateral eye | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | All Randomized Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 12.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 13 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility
Mean diurnal change from baseline in trabecular (tonographic) outflow facility.
Time frame: Study treatment was administered for 7 days, and outcome measures collected on Day 8
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Netarsudil Ophthalmic Solution 0.02% | Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility | 0.039 mcl/min/mmHg | Standard Deviation 0.0401 |
| Placebo Comparator | Mean Change From Baseline in the Mean Diurnal Trabecular Outflow Facility | 0.007 mcl/min/mmHg | Standard Deviation 0.0275 |
Comparison: Mean Change from Baselinep-value: 0.001t-test, 1 sided
Primary
Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility.
Mean diurnal change from baseline in trabecular (tonographic) outflow facility.
Time frame: Study treatment was administered for 7 days, and outcome measures collected on Day 8
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Netarsudil Ophthalmic Solution 0.02% | Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility. | 34.589 percentage change | Standard Deviation 34.5935 |
| Placebo Comparator | Mean Percent Change From Baseline in the Mean Diurnal Trabecular Outflow Facility. | 9.597 percentage change | Standard Deviation 25.6334 |
Comparison: Mean change from baseline (percent difference from baseline)p-value: 0.0003t-test, 1 sided
Secondary
Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)
Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)
Time frame: Study treatment was administered for 7 days, and outcome measures collected on Day 8
Population: Modified intent-to-treat (mITT) population, EVP analyzed in 9 participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Netarsudil Ophthalmic Solution 0.02% | Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Diurnal EVP (delta vs.baseline) | -0.787 mmHg | Standard Deviation 0.8372 |
| Netarsudil Ophthalmic Solution 0.02% | Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Diurnal IOP (delta vs.baseline) | -4.521 mmHg | Standard Deviation 1.5842 |
| Placebo Comparator | Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Diurnal EVP (delta vs.baseline) | 0.103 mmHg | Standard Deviation 0.7094 |
| Placebo Comparator | Mean Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Diurnal IOP (delta vs.baseline) | -0.979 mmHg | Standard Deviation 1.6009 |
Comparison: Mean change from baseline -EVPp-value: 0.0687t-test, 1 sided
Comparison: Mean change from baseline -IOPp-value: <0.0001t-test, 1 sided
Secondary
Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP)
Mean diurnal change from baseline in mean diurnal IOP measured using a Pneumatonometer and mean diurnal EVP using a custom-modified slit-lamp mounted venomanometer. (EVP conducted at a single site in only 9 participants)
Time frame: Study treatment was administered for 7 days, and outcome measures collected on Day 8
Population: Modified intent-to-treat (mITT) population, EVP analyzed in 9 participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Netarsudil Ophthalmic Solution 0.02% | Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Percent change from baseline (EVP) | -9.465 percentage change | Standard Deviation 9.5044 |
| Netarsudil Ophthalmic Solution 0.02% | Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Percent change from baseline (IOP) | -19.568 percentage change | Standard Deviation 6.0713 |
| Placebo Comparator | Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Percent change from baseline (IOP) | -4.227 percentage change | Standard Deviation 6.9699 |
| Placebo Comparator | Mean Percent Change From Baseline in Episcleral Venous Pressure (EVP) and in Intraocular Pressure (IOP) | Percent change from baseline (EVP) | 3.103 percentage change | Standard Deviation 7.7322 |
Comparison: Mean change from baseline (percent difference from baseline) -EVPp-value: 0.0087t-test, 1 sided
Comparison: Mean change from baseline (percent difference from baseline)- IOPp-value: <0.0001t-test, 1 sided