Ocular Hypertension, Primary Open Angle Glaucoma
Conditions
Keywords
Glaucoma, Primary Open-Angle Glaucoma, Ocular Hypertension
Brief summary
A Phase 3 Study Comparing the Efficacy and Safety of Netarsudil Ophthalmic Solution 0.02% QD to Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% BID, for Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Over A 4-Week Period.
Interventions
Topical sterile ophthalmic solution Other Name: Rhopressa®
DRUGRipasudil hydrochloride hydrate ophthalmic solution 0.4%
Other Name: Glanatec®
Sponsors
Aerie Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study adopted a single-masked study design. Treatment assignments were masked to the Investigator, the clinical study team (Sponsor, designated personnel involved in day-to-day study management, Monitors, Data Managers, and Statisticians), and the subjects for the duration of the study. The netarsudil and ripasudil bottles were different in the study, however, investigators and subjects were masked to study drug assignment.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 20 years of age or older * Diagnosis of POAG or OHT in both eyes (POAG in one eye and OHT in the fellow eye was acceptable) * Medicated intraocular pressure (IOP) ≥ 14 mmHg in at least one eye and \< 30 mmHg in both eyes at screening visit * For POAG eyes, unmedicated (post washout) IOP ≥ 15 mmHg and \< 35 mmHg in the study eye at 2 qualification visits (09:00 hours), 2-7 days apart. At second qualification visit IOP ≥ 15 mmHg and \< 35 mmHg at 11:00 and 16:00 hour (in the same eye). * For OHT eyes, unmedicated (post washout) IOP ≥ 22 mmHg and \< 35 mmHg in the study eye at 2 qualification visits (09:00 hours), 2-7 days apart. At second qualification visit IOP ≥ 22 mmHg and \< 35 mmHg at 11:00 and 16:00 hours (in the same eye) * Best-corrected visual acuity (BCVA) +0.7 log MAR or better (20/100 Snellen or better or 0.20 or better in decimal unit) in each eye * Willingness and ability to give signed informed consent and follow study instructions
Exclusion criteria
* Clinically significant ocular disease * Retinal diseases that may progress during the study period * Pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure glaucoma, or narrow angles * Previous glaucoma intraocular surgery * Refractive surgery in either eye * Ocular hyperemia score of moderate (+2) or severe (+3) at Qualification Visit #2 * Ocular trauma * Ocular infection or inflammation * Any corneal disease that may confound assessment * Evidence of corneal deposits or cornea verticillata * Known hypersensitivity to any component of netarsudil ophthalmic solution 0.02%, ripasudil hydrochloride hydrate ophthalmic solution 0.4%, or to topical anesthetic. * Mean central corneal thickness \>620 um * Any abnormality preventing reliable Goldmann applanation tonometry of either eye (e.g. keratoconus) * Cannot demonstrate proper delivery of the eye drop * Clinically significant systemic disease * Participation in any investigational study within 30 days prior to screening * Women of childbearing potential 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) | 29 Days | Comparison of both groups mean diurnal IOP at Week 4 (Day 29). IOP will be measured by Goldmann applanation tonometry and reported in millimeters mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Mean diurnal IOP was calculated as the average of 3 IOP values across 09:00, 11:00 and 16:00 time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IOP at Weeks 1 and 2 | Day 8, Day 15 | Mean diurnal IOP as measured in mmHg at each post-treatment visit. |
| Mean Change IOP From Baseline at Days 8, 15, 29 | Baseline (Day 1), Days 8, 15, 29 | Mean change from baseline in mean diurnal IOP as measured in mmHg at each post-treatment visit. |
Countries
Japan
Participant flow
Recruitment details
Recruitment took place at 27 clinic sites in Japan starting on 30Nov2020 with last subject last visit on 30July2021.
Pre-assignment details
Subjects were required to washout of their pre-study ocular hypotensive medication for a prescribed period as specified in the protocol prior to attending Qualification Visit #1.
Participants by arm
| Arm | Count |
|---|---|
| Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle 1 drop netarsudil 0.02% in the evening and 1 drop netarsudil vehicle in the morning in each eye.
Netarsudil ophthalmic solution 0.02%: Topical sterile ophthalmic solution Other Name: Rhopressa® | 122 |
| Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% 1 drop ripasudil twice daily in the morning and evening in each eye.
Ripasudil hydrochloride hydrate ophthalmic solution 0.4%: Other Name: Glanatec® | 123 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Study Completion | Adverse Event | 2 | 3 |
| Study Completion | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% | Total | Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle |
|---|---|---|---|
| Age, Customized Age Category < 65 years | 60 Participants | 123 Participants | 63 Participants |
| Age, Customized Age Category >= 65 years | 63 Participants | 122 Participants | 59 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 66 Participants | 144 Participants | 78 Participants |
| Sex: Female, Male Male | 57 Participants | 101 Participants | 44 Participants |
| Study Eye Diagnosis Ocular Hypertension | 35 Participants | 67 Participants | 32 Participants |
| Study Eye Diagnosis Primary Open Angle Glaucoma | 88 Participants | 178 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 122 | 0 / 123 |
| other Total, other adverse events | 73 / 122 | 82 / 123 |
| serious Total, serious adverse events | 0 / 122 | 2 / 123 |
Outcome results
Primary
Intraocular Pressure (IOP)
Comparison of both groups mean diurnal IOP at Week 4 (Day 29). IOP will be measured by Goldmann applanation tonometry and reported in millimeters mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Mean diurnal IOP was calculated as the average of 3 IOP values across 09:00, 11:00 and 16:00 time points.
Time frame: 29 Days
Population: The intent-to-treat (ITT) population was used for the primary analysis of the efficacy variables and included all randomized subjects (as randomized) who received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle | Intraocular Pressure (IOP) | 15.96 mmHg | Standard Error 0.157 |
| Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% | Intraocular Pressure (IOP) | 17.71 mmHg | Standard Error 0.155 |
p-value: <0.0000195% CI: [-2.17, -1.31]ANCOVA
Secondary
IOP at Weeks 1 and 2
Mean diurnal IOP as measured in mmHg at each post-treatment visit.
Time frame: Day 8, Day 15
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle | IOP at Weeks 1 and 2 | Mean diurnal IOP at Weeks 2 (Days 15) | 16.02 mmHg | Standard Error 0.168 |
| Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle | IOP at Weeks 1 and 2 | Mean diurnal IOP at Weeks 1 (Days 8) | 16.28 mmHg | Standard Error 0.143 |
| Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% | IOP at Weeks 1 and 2 | Mean diurnal IOP at Weeks 2 (Days 15) | 17.83 mmHg | Standard Error 0.166 |
| Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% | IOP at Weeks 1 and 2 | Mean diurnal IOP at Weeks 1 (Days 8) | 17.87 mmHg | Standard Error 0.141 |
Secondary
Mean Change IOP From Baseline at Days 8, 15, 29
Mean change from baseline in mean diurnal IOP as measured in mmHg at each post-treatment visit.
Time frame: Baseline (Day 1), Days 8, 15, 29
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle | Mean Change IOP From Baseline at Days 8, 15, 29 | Baseline IOP mean diurnal IOP | 20.475 mmHg | Standard Error 0.251 |
| Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle | Mean Change IOP From Baseline at Days 8, 15, 29 | V4: Week 1 (Day 8) Change from Baseline | -4.341 mmHg | Standard Error 0.1603 |
| Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle | Mean Change IOP From Baseline at Days 8, 15, 29 | V5: Week 2 (Day 15) Change from Baseline | -4.601 mmHg | Standard Error 0.1728 |
| Netarsudil Ophthalmic Solution 0.02% and Netarsudil Ophthalmic Solution Vehicle | Mean Change IOP From Baseline at Days 8, 15, 29 | V6: Week 4 (Day 29) Change from Baseline | -4.653 mmHg | Standard Error 0.1701 |
| Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% | Mean Change IOP From Baseline at Days 8, 15, 29 | V6: Week 4 (Day 29) Change from Baseline | -2.983 mmHg | Standard Error 0.1622 |
| Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% | Mean Change IOP From Baseline at Days 8, 15, 29 | Baseline IOP mean diurnal IOP | 20.830 mmHg | Standard Error 0.3198 |
| Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% | Mean Change IOP From Baseline at Days 8, 15, 29 | V5: Week 2 (Day 15) Change from Baseline | -2.852 mmHg | Standard Error 0.1759 |
| Ripasudil Hydrochloride Hydrate Ophthalmic Solution 0.4% | Mean Change IOP From Baseline at Days 8, 15, 29 | V4: Week 1 (Day 8) Change from Baseline | -2.814 mmHg | Standard Error 0.1397 |