Ocular Hypertension, Open Angle Glaucoma
Conditions
Keywords
Glaucoma
Brief summary
Double-masked, randomized, multi-center, dose-response, active-controlled parallel-comparison of AR-13324 to latanoprost
Interventions
Administered to study eye, once daily (QD) in the evening (PM) for 28 days
Administered to study eye, QD in the PM for 28 days
Administered to study eye, QD in the PM for 28 days
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 99 Years
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or greater. 2. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). 3. Unmedicated (post-washout) Intraocular Pressure (IOP) ≥ 24 mm Hg at 2 eligibility visits (08:00 hr), 2-7 days a part, and ≥ 22 mm Hg at 10:00 and 16:00 hrs at the second qualification visit. If only one eye meets the IOP criteria it must be the same eye that met the criteria at all the qualification timepoints. 4. Corrected visual acuity in each eye +1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200). 5. Able and willing to give signed informed consent and follow study instructions.
Exclusion criteria
Ophthalmic 1. Glaucoma: pseudoexfoliation or pigment dispersion component, history of angle closure or narrow angles. Note: Previous laser peripheral iridotomy is NOT acceptable. 2. IOP \> 36 mm Hg. 3. Known hypersensitivity to any component of the formulation (benzalkonium chloride, etc.), or to topical anesthetics. 4. Previous glaucoma intraocular surgery or glaucoma laser procedures in study eye(s, e.g., laser trabeculoplasty). 5. Refractive surgery in study eye(s) (e.g., radial keratotomy, photorefractive keratectomy (PRK), laser eye surgery (LASIK), etc.). 6. Ocular trauma within the past six months, or ocular surgery or laser treatment within the past three months prior to screening. 7. Evidence of ocular infection, inflammation, clinically significant blepharitis or conjunctivitis at screening (Visit 0), or a history of herpes simplex keratitis 8. Ocular medication of any kind within 30 days of Visit 0, with the exception of a) ocular hypotensive medications (which must be washed out according to the provided schedule), b) lid scrubs (which may be used prior to, but not after Visit 0) or c) lubricating drops for dry eye (which may be used throughout the study). 9. Clinically significant ocular disease (e.g. uveitis, severe keratoconjunctivitis sicca) which might interfere with the study, including glaucomatous damage so severe that washout of ocular hypotensive medications for one month is not judged safe (i.e., cup-disc ratio \> 0.8). 10. Central corneal thickness greater than 600 µm. 11. Any abnormality preventing reliable applanation tonometry of either eye. Systemic: 12. Clinically significant abnormalities (as determined by the treating physician) in laboratory tests at screening. 13. Known hypersensitivity or contraindication to latanoprost. 14. Clinically significant systemic disease (e.g., myasthenia gravis, hepatic, renal, endocrine or cardiovascular disorders) which might interfere with the study. 15. Participation in any investigational study within 30 days prior to screening. 16. Changes of systemic medication that could have a substantial effect on IOP within 30 days prior to screening, or anticipated during the study. 17. Due to the current status of the preclinical safety program, women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. An adult woman is considered to be of childbearing potential unless she is one year post-menopausal or three months post-surgical sterilization. All females of childbearing potential must have a negative urine pregnancy test result at the screening examination and must not intend to become pregnant during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure (IOP) | Study treatment was administered for 28 days | The primary efficacy endpoint was the mean IOP across subjects within treatment group on each day at each post-treatment timepoint. IOP was measured at 0800, 1000, and 1600 hours on days 0, 14, and 28. IOP was also measured at 0800 hours on Day 7 and follow-up days 29 and 30. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Exposure | 28 Days | Exposure to study medication in days for all treatment groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AR-13324 Ophthalmic Solution 0.01% 1 drop to study eye once daily (QD) in the evening (PM) | 75 |
| AR-13324 Ophthalmic Solution 0.02% 1 drop to study eye once daily (QD) in the evening (PM) | 72 |
| Latanoprost Ophthalmic Solution 0.005% 1 drop to study eye once daily (QD) in the evening (PM) | 77 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 |
| Overall Study | Elevated IOP | 1 | 0 | 0 |
| Overall Study | Inappropriate use of study medications | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Non-Compliant | 0 | 1 | 0 |
| Overall Study | Test Agent Discontinuation | 0 | 1 | 0 |
| Overall Study | Uncontrolled Intraocular Pressure (IOP) | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | AR-13324 Ophthalmic Solution 0.01% | AR-13324 Ophthalmic Solution 0.02% | Latanoprost Ophthalmic Solution 0.005% | Total |
|---|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 11.54 | 66.3 years STANDARD_DEVIATION 10.25 | 65.7 years STANDARD_DEVIATION 11.82 | 65.1 years STANDARD_DEVIATION 11.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 15 Participants | 15 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 57 Participants | 62 Participants | 178 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 | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 16 Participants | 19 Participants | 52 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 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 | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 56 Participants | 53 Participants | 58 Participants | 167 Participants |
| Sex: Female, Male Female | 42 Participants | 45 Participants | 45 Participants | 132 Participants |
| Sex: Female, Male Male | 33 Participants | 27 Participants | 32 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 75 | 0 / 72 | 0 / 77 |
| other Total, other adverse events | 43 / 75 | 45 / 72 | 18 / 77 |
| serious Total, serious adverse events | 1 / 75 | 0 / 72 | 2 / 77 |
Outcome results
Primary
Intraocular Pressure (IOP)
The primary efficacy endpoint was the mean IOP across subjects within treatment group on each day at each post-treatment timepoint. IOP was measured at 0800, 1000, and 1600 hours on days 0, 14, and 28. IOP was also measured at 0800 hours on Day 7 and follow-up days 29 and 30.
Time frame: Study treatment was administered for 28 days
Population: Modified intent to treat (mITT) population (3 subjects were excluded, leaving 221)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 0, 0800 hours | 27.34 mmHg | Standard Deviation 3.529 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 0, 1000 hours | 25.55 mmHg | Standard Deviation 3.411 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 0, 1600 hours | 24.49 mmHg | Standard Deviation 3.128 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 7, 0800 hours | 21.89 mmHg | Standard Deviation 4.672 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 14, 0800 hours | 21.24 mmHg | Standard Deviation 4.295 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 14, 1000 hours | 19.28 mmHg | Standard Deviation 3.581 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 14, 1600 hours | 18.90 mmHg | Standard Deviation 3.578 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 28, 0800 hours | 21.95 mmHg | Standard Deviation 4.717 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 28, 1000 hours | 19.69 mmHg | Standard Deviation 4.358 |
| AR-13324 Ophthalmic Solution 0.01% | Intraocular Pressure (IOP) | Day 28, 1600 hours | 18.82 mmHg | Standard Deviation 3.281 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 28, 1000 hours | 19.53 mmHg | Standard Deviation 3.726 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 0, 0800 hours | 27.11 mmHg | Standard Deviation 3.031 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 14, 1000 hours | 18.88 mmHg | Standard Deviation 3.461 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 14, 0800 hours | 20.80 mmHg | Standard Deviation 3.679 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 0, 1000 hours | 25.41 mmHg | Standard Deviation 3.024 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 28, 1600 hours | 19.13 mmHg | Standard Deviation 3.656 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 28, 0800 hours | 21.24 mmHg | Standard Deviation 4.034 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 0, 1600 hours | 24.29 mmHg | Standard Deviation 2.602 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 14, 1600 hours | 18.72 mmHg | Standard Deviation 3.585 |
| AR-13324 Ophthalmic Solution 0.02% | Intraocular Pressure (IOP) | Day 7, 0800 hours | 21.15 mmHg | Standard Deviation 4.047 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 28, 0800 hours | 19.24 mmHg | Standard Deviation 2.899 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 7, 0800 hours | 20.03 mmHg | Standard Deviation 3.173 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 14, 0800 hours | 19.30 mmHg | Standard Deviation 3.033 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 14, 1000 hours | 18.09 mmHg | Standard Deviation 2.884 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 28, 1000 hours | 18.40 mmHg | Standard Deviation 2.994 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 14, 1600 hours | 17.86 mmHg | Standard Deviation 2.977 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 0, 0800 hours | 26.78 mmHg | Standard Deviation 2.749 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 28, 1600 hours | 18.34 mmHg | Standard Deviation 3.052 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 0, 1000 hours | 25.18 mmHg | Standard Deviation 2.719 |
| Latanoprost Ophthalmic Solution 0.005% | Intraocular Pressure (IOP) | Day 0, 1600 hours | 24.58 mmHg | Standard Deviation 2.515 |
Secondary
Extent of Exposure
Exposure to study medication in days for all treatment groups.
Time frame: 28 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AR-13324 Ophthalmic Solution 0.01% | Extent of Exposure | 27.6 days | Standard Deviation 4.07 |
| AR-13324 Ophthalmic Solution 0.02% | Extent of Exposure | 26.8 days | Standard Deviation 4.6 |
| Latanoprost Ophthalmic Solution 0.005% | Extent of Exposure | 27.8 days | Standard Deviation 1.35 |