Presbyopia
Conditions
Keywords
Nyxol, Presbyopia, Pilocarpine
Brief summary
The objectives of this study are: To evaluate the safety and efficacy of Nyxol alone and with adjunctive low dose pilocarpine to improve distance-corrected near visual acuity (DCNVA) in subjects with presbyopia.
Detailed description
This is a Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Study of the Safety and Efficacy of Nyxol (Phentolamine Ophthalmic Solution 0.75%) as a Single Agent and With Adjunctive Low-Dose Pilocarpine Hydrochloride Ophthalmic Solution 0.4% in Subjects With Presbyopia
Interventions
DRUGPhentolamine Opthalmic Solution 0.75%
phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist
OTHERPlacebo
Vehicle for Phentolamine Ophthalmic Solution
DRUGLow dose pilocarpine
Pilocarpine hydrochloride ophthalmic solution 0.4%
OTHERLow dose pilocarpine vehicle
Vehicle for low dose pilocarpine
Sponsors
Ocuphire Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females ≥ 40 and ≤ 64 years of age. 2. BCDVA of 0.1 LogMAR (20/25 Snellen equivalent) or better in each eye in photopic conditions. 3. DCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse but not \> 0.7 LogMAR (20/100 Snellen equivalent) in photopic conditions in each eye and binocularly. 4. For subjects who depend on reading glasses or bifocals, binocular best-corrected near VA is 0.1 LogMAR (20/25 Snellen equivalent) or better. 5. Photopic PD of ≥ 3 mm in either eye.
Exclusion criteria
Ophthalmic (in either eye): 1. Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of Screening until study completion, with the exception of lid scrubs with OTC products and artificial tears as specified in Exclusion # 2 below. 2. Use of any OTC artificial tears (preserved or unpreserved) during Visit days or 15 min before or after instillation of study medication. 3. Current use of any topical ophthalmic therapy for dry eye. 4. Tear break-up time of \< 5 seconds or corneal fluorescein staining Grade ≥ 2 in the inferior zone or Grade ≥ 1 in the central zone using the National Eye Institute scale.. 5. Clinically significant ocular disease that might interfere with the study as deemed by the Investigator. 6. Recent or current evidence of ocular infection or inflammation in either eye. 7. Any history of herpes simplex or herpes zoster keratitis. 8. Known allergy, hypersensitivity, or contraindication to any component of the phentolamine, pilocarpine, or vehicle formulations. 9. Prior participation in a study involving the use of Nyxol for the treatment of presbyopia. 10. History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal. 11. Ocular trauma within 6 months prior to Screening. 12. Ocular surgery or any ocular laser treatment within 6 months prior to Screening. 13. Subjects with surgical monovision, multifocal or extended depth of focus intraocular lenses (IOLs) are excluded. 14. History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris. 15. Contact lens wear on the day of any study visit and contact lenses must be removed for home dosing and for at least 10 minutes following dosing. Systemic: 16. Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists . 17. Known hypersensitivity or contraindication to any systemic cholinergic parasympathomimetic agent. 18. Clinically significant systemic disease that might interfere with the study as deemed by the judgment of the Investigator. 19. Initiation of treatment with, or any changes to, the current dosage, drug, or regimen of any systemic adrenergic or cholinergic drugs within 7 days prior to Screening or during the study. 20. Participation in any investigational study within 30 days prior to Screening. 21. Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. 22. Resting HR outside the range of 50 to 110 beats per min. 23. Hypertension with resting diastolic BP \> 105 mmHg or systolic BP \> 160 mmHg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA and With < 5 Letters of Loss in Photopic Binocular BCDVA in Nyxol-treated Subjects | Baseline at 30 min post-LDP/vehicle comparing subjects treated with Nyxol + LDP to subjects treated with placebo + LDP vehicle at Visit 5 (Stage 2 Day 8) | The primary efficacy endpoint is the percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with \< 5 letters of loss in photopic binocular BCDVA from Baseline at 30 min post-LDP/vehicle comparing subjects treated with Nyxol + LDP to subjects treated with placebo + LDP vehicle at Visit 5 (Stage 2 Day 8). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nyxol + Low Dose Pilocarpine Phentolamine Opthalmic Solution 0.75%: phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist
Low dose pilocarpine: Pilocarpine hydrochloride ophthalmic solution 0.4% | 82 |
| Nyxol + Low Dose Pilocarpine Vehicle Phentolamine Opthalmic Solution 0.75%: phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist
Low dose pilocarpine vehicle: Vehicle for low dose pilocarpine | 81 |
| Placebo + Low Dose Pilocarpine Placebo: Vehicle for Phentolamine Ophthalmic Solution
Low dose pilocarpine: Pilocarpine hydrochloride ophthalmic solution 0.4% | 82 |
| Placebo + Low Dose Pilocarpine Vehicle Placebo: Vehicle for Phentolamine Ophthalmic Solution
Low dose pilocarpine vehicle: Vehicle for low dose pilocarpine | 82 |
| Total | 327 |
Baseline characteristics
| Characteristic | Nyxol + Low Dose Pilocarpine | Total | Placebo + Low Dose Pilocarpine Vehicle | Placebo + Low Dose Pilocarpine | Nyxol + Low Dose Pilocarpine Vehicle |
|---|---|---|---|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 5.22 | 54.6 years STANDARD_DEVIATION 5.33 | 54.4 years STANDARD_DEVIATION 4.99 | 54.3 years STANDARD_DEVIATION 5.92 | 55.4 years STANDARD_DEVIATION 5.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 56 Participants | 18 Participants | 12 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 271 Participants | 64 Participants | 70 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 57 Participants | 10 Participants | 15 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 64 Participants | 262 Participants | 69 Participants | 65 Participants | 64 Participants |
| Region of Enrollment United States | 82 participants | 327 participants | 82 participants | 82 participants | 81 participants |
| Sex: Female, Male Female | 56 Participants | 236 Participants | 61 Participants | 64 Participants | 55 Participants |
| Sex: Female, Male Male | 26 Participants | 91 Participants | 21 Participants | 18 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 79 | 0 / 80 | 0 / 81 | 0 / 82 |
| other Total, other adverse events | 13 / 79 | 12 / 80 | 18 / 81 | 13 / 82 |
| serious Total, serious adverse events | 0 / 79 | 0 / 80 | 0 / 81 | 0 / 82 |
Outcome results
Primary
Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA and With < 5 Letters of Loss in Photopic Binocular BCDVA in Nyxol-treated Subjects
The primary efficacy endpoint is the percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with \< 5 letters of loss in photopic binocular BCDVA from Baseline at 30 min post-LDP/vehicle comparing subjects treated with Nyxol + LDP to subjects treated with placebo + LDP vehicle at Visit 5 (Stage 2 Day 8).
Time frame: Baseline at 30 min post-LDP/vehicle comparing subjects treated with Nyxol + LDP to subjects treated with placebo + LDP vehicle at Visit 5 (Stage 2 Day 8)
Population: Modified Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nyxol + Low Dose Pilocarpine | Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA and With < 5 Letters of Loss in Photopic Binocular BCDVA in Nyxol-treated Subjects | 27 Participants |
| Nyxol + Low Dose Pilocarpine Vehicle | Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA and With < 5 Letters of Loss in Photopic Binocular BCDVA in Nyxol-treated Subjects | 31 Participants |
| Placebo + Low Dose Pilocarpine | Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA and With < 5 Letters of Loss in Photopic Binocular BCDVA in Nyxol-treated Subjects | 16 Participants |
| Placebo + Low Dose Pilocarpine Vehicle | Percent of Subjects With ≥ 15 Letters of Improvement in Photopic Binocular DCNVA and With < 5 Letters of Loss in Photopic Binocular BCDVA in Nyxol-treated Subjects | 22 Participants |
p-value: <0.0195% CI: [1.23, 4.2]t-test, 2 sided