Ocular Hypertension, Open Angle Glaucoma
Conditions
Keywords
Open Angle Glaucoma, Ocular Hypertension
Brief summary
The objectives of this study are: * To evaluate the efficacy of Phentolamine Mesylate to lower intra-ocular pressure (IOP) in the treatment of Open-Angle Glaucoma (OAG) and Ocular Hypertension (OHT). * To evaluate the ocular and systemic safety of Phentolamine Mesylate compared to its vehicle. * To evaluate additional efficacy of Phentolamine Mesylate to improve visual performance.
Detailed description
Placebo-controlled double-masked, multiple dose Phase 2 study in 40 patients with IOP ≥ 22 and ≤30 mmHg, evaluating ocular and systemic safety and efficacy following administration of Phentolamine mesylate 1.0% QD at 8PM to 10PM in both eyes for 14 days.
Interventions
Topical Sterile Ophthalmic Solution
Topical Sterile Ophthalmic Solution
Sponsors
Ocuphire Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or greater 2. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). A reported history of untreated OHT with IOP ≥22mmHg and ≤ 30mmHg is preferred. 3. Untreated or treated OAG/OHT with 2 or fewer ocular hypotensive medications. 4. Untreated (post-washout) mean IOP ≥ 22mmHg and ≤30mmHg in the study eye at the Qualification Visit (8AM). 5. Corrected visual acuity in each eye +1.0 logMAR or better by Early Treatment Diabetic Retinopathy Study (ETDRS) in each eye (equivalent to 20/200 or better) at the Screening Visit and Qualification Visit. 6. Otherwise healthy and well-controlled subjects. 7. Able and willing to give signed informed consent and follow study instructions. 8. Able to self-administer study medication or to have study medication administered by a caregiver throughout the study period.
Exclusion criteria
1. Closed or very narrow angles (Grade 0-1, Shaffer) 2. Glaucoma: pseudo-exfoliation or pigment dispersion component 3. Known hypersensitivity to any α-adrenoceptor antagonists 4. Previous laser and/or non-laser glaucoma surgery or procedure in either eye 5. Refractive surgery in either eye 6. Ocular trauma in either eye within the 6 months prior to Screening, or ocular surgery or non-refractive laser treatment within the 3 months prior to Screening 7. Recent or current evidence of ocular infection or inflammation in either eye 8. Ocular medication in either eye of any kind within 30 days of Screening 9. Clinically significant ocular disease in either eye 10. History of diabetic retinopathy 11. Contact lens wear within 3 days prior to and for the duration of the study 12. Central corneal thickness in either eye \>600 μm at Screening 13. Any abnormality in either eye preventing reliable applanation tonometry 14. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists 15. Clinically significant systemic disease that might interfere with the study 16. Participation in any investigational study within 30 days prior to Screening 17. Use of any topical or systemic adrenergic or cholinergic drugs up to 30 days prior to Screening, or during the study 18. Changes in systemic medication that could have an effect on IOP within 30 days prior to Screening 19. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control 20. Resting heart rate outside the normal range (50-110 beats per minute) at Screening or Qualification Visit 21. Hypertension with resting diastolic blood pressure (BP) \> 105 mmHg or systolic BP \> 160 mmHg at the Screening or Qualification Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure | 15 days | change from Baseline in mean diurnal IOP in the study eye |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pupil Diameter | 15 days | Change from Baseline Pupil Diameter (Photopic Conditions) |
| Distance Visual Acuity | 15 days | Percentage of Subjects Achieving ≥1 line improvement in Distance Visual Acuity from Baseline measured at 4 meters (photopic conditions) |
| Conjunctival Hyperemia | 15 days | Conjunctival Hyperemia Category |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nyxol Ophthalmic Solution 1% 1 drop in each eye daily (QD) at or before bedtime (8pm to 10pm) for 14 days
Phentolamine Mesylate Ophthalmic Solution 1%: Topical Sterile Ophthalmic Solution | 19 |
| Nyxol Ophthalmic Solution Vehicle 1 drop in each eye daily (QD) at or before bedtime (8pm to 10pm) for 14 days
Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo): Topical Sterile Ophthalmic Solution | 20 |
| Total | 39 |
Baseline characteristics
| Characteristic | Nyxol Ophthalmic Solution 1% | Nyxol Ophthalmic Solution Vehicle | Total |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 13.23 | 63.2 years STANDARD_DEVIATION 10.35 | 60.7 years STANDARD_DEVIATION 11.97 |
| Baseline Intraocular Pressure (Study Eye) | 23.43 mmHg STANDARD_DEVIATION 1.675 | 24.38 mmHg STANDARD_DEVIATION 2.097 | 23.92 mmHg STANDARD_DEVIATION 1.939 |
| Race/Ethnicity, Customized Non-White | 8 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 14 Participants | 25 Participants |
| Sex: Female, Male Female | 9 Participants | 13 Participants | 22 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 20 |
| other Total, other adverse events | 5 / 19 | 1 / 20 |
| serious Total, serious adverse events | 0 / 19 | 0 / 20 |
Outcome results
Primary
Intraocular Pressure
change from Baseline in mean diurnal IOP in the study eye
Time frame: 15 days
Population: Patients underwent a Screening visit where they were included in the trial if they were at least 18 years of age with either OHT in both eyes or OAG in 1 eye with OHT in the fellow eye, which was previously untreated or treated with ≤2 ocular hypotensive medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nyxol Ophthalmic Solution 1% | Intraocular Pressure | -2.30 mmHg | Standard Deviation 2.986 |
| Nyxol Ophthalmic Solution Vehicle | Intraocular Pressure | -2.18 mmHg | Standard Deviation 1.856 |
p-value: 0.89t-test, 2 sided
Secondary
Conjunctival Hyperemia
Conjunctival Hyperemia Category
Time frame: 15 days
Population: Full analytical sample
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nyxol Ophthalmic Solution 1% | Conjunctival Hyperemia | None | 4 Participants |
| Nyxol Ophthalmic Solution 1% | Conjunctival Hyperemia | Mild | 10 Participants |
| Nyxol Ophthalmic Solution 1% | Conjunctival Hyperemia | Moderate | 3 Participants |
| Nyxol Ophthalmic Solution 1% | Conjunctival Hyperemia | Severe | 2 Participants |
| Nyxol Ophthalmic Solution Vehicle | Conjunctival Hyperemia | Severe | 0 Participants |
| Nyxol Ophthalmic Solution Vehicle | Conjunctival Hyperemia | None | 8 Participants |
| Nyxol Ophthalmic Solution Vehicle | Conjunctival Hyperemia | Moderate | 4 Participants |
| Nyxol Ophthalmic Solution Vehicle | Conjunctival Hyperemia | Mild | 8 Participants |
Secondary
Distance Visual Acuity
Percentage of Subjects Achieving ≥1 line improvement in Distance Visual Acuity from Baseline measured at 4 meters (photopic conditions)
Time frame: 15 days
Population: Full Analysis Data Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nyxol Ophthalmic Solution 1% | Distance Visual Acuity | 12 Participants |
| Nyxol Ophthalmic Solution Vehicle | Distance Visual Acuity | 4 Participants |
Secondary
Pupil Diameter
Change from Baseline Pupil Diameter (Photopic Conditions)
Time frame: 15 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nyxol Ophthalmic Solution 1% | Pupil Diameter | Day 8 (8AM) | -0.77 mm | Standard Deviation 0.538 |
| Nyxol Ophthalmic Solution 1% | Pupil Diameter | Day 15 (8AM) | -0.77 mm | Standard Deviation 0.55 |
| Nyxol Ophthalmic Solution Vehicle | Pupil Diameter | Day 15 (8AM) | -0.01 mm | Standard Deviation 0.58 |
| Nyxol Ophthalmic Solution Vehicle | Pupil Diameter | Day 8 (8AM) | -0.07 mm | Standard Deviation 0.555 |