Dilation, Mydriasis
Conditions
Keywords
Nyxol, Pharmacologically Induced Mydriasis, Dilation
Brief summary
The objectives of this study are: * To evaluate the efficacy of Nyxol to expedite the reversal of pharmacologically-induced mydriasis across multiple mydriatic agents with an emphasis on phenylephrine * To evaluate the efficacy of Nyxol to return subjects to baseline accommodation after worsening (with cycloplegic agents tropicamide and Paremyd) * To evaluate the safety of Nyxol * To evaluate any additional benefits of the reversal of pharmacologically-induced mydriasis * To evaluate the systemic exposure of Nyxol on pharmacokinetic (PK) sampling
Detailed description
A randomized, parallel arm, double-masked, placebo-controlled Phase 3 study in at least 330 randomized subjects, evaluating the safety and efficacy of Nyxol in subjects with pharmacologically-induced mydriasis. Following the successful completion of screening, each subject will be stratified by eye color and then simultaneously be randomized to mydriatic agent (unmasked) and treatment (masked). Treatment randomization will be 2:1, Nyxol or placebo (vehicle). Stratification by iris color will be 1:1, light or dark rides. The mydriatic agent randomization will be 3:1:1 (2.5% phenylephrine, 1% tropicamide, and Paremyd). At the treatment visit, subjects who have been randomized and stratified by iris color (1:1 \[light/dark\]) will receive one of three approved mydriatic agents approximately 1 hour prior to receiving study treatment. Measurements will be measured before (-1 hour /baseline) and 60 minutes after (maximum/0 minutes) the mydriatic agent instillation in each eye (i.e. right before the study treatment is administered), and at 30 minutes, 60 minutes, 90 minutes, 2 hours, 3 hours, 4 hours, and 6 hours after treatment dosing. Measurements will include pupil diameter (PD), distance and near visual acuity (VA), accommodation, and redness in each eye. Blood sampling for Nyxol PK measurements will be conducted in a subset of approximately 30 adult subjects at approximately two select study sites. At the Follow-Up Visit, which is 1 day after Visit 1, measurements will again be recorded 24 hours after treatment dosing.
Interventions
0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist
Phentolamine Ophthalmic Solution Vehicle
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
12 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Males or females ≥ 12 years of age 2. Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits
Exclusion criteria
1. Clinically significant ocular disease as deemed by the Investigator (eg, glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca) that might interfere with the study 2. Unwilling or unable to discontinue use of contact lenses at screening until study completion 3. Unwilling or unable to suspend use of topical medication at screening until study completion 4. Ocular trauma, ocular surgery, or non-refractive laser treatment within the 6 months prior to screening 5. Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of screening, with the exception of lid scrubs with OTC products (eg, OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.) 6. Recent or current evidence of ocular infection or inflammation in either eye (such as current evidence of clinically significant blepharitis, conjunctivitis, or keratitis). Subjects must be symptom-free for at least 7 days prior to screening 7. Closed or very narrow-angle that in the Investigator's opinion is potentially occludable if the subject's pupil is dilated 8. Prior participation in a study involving the use of Nyxol for the reversal of mydriasis 9. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists 10. Clinically significant systemic disease (eg, uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that might interfere with the study 11. Participation in any investigational study within 30 days prior to screening 12. Resting heart rate (HR) outside the normal range (50-110 beats per minute) at the Screening Visit. 13. Hypertension with resting diastolic blood pressure (BP)\>105 mmHg or systolic BP \> 160 mmHg at the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 90 minutes | Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 30 minutes to 24 hours | Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter |
| Pupil Diameter (Change From Max) | 30 minutes to 24 hours | Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes) |
| Percent of Subjects With Unchanged Accommodation From Baseline | 90 minutes to 6 Hours | Percentage of subjects with unchanged accommodation from baseline (-1 hour) |
| Change From Baseline in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Without Glare Conditions | 6 hours | Change from Baseline in best-corrected distance visual acuity (BCDVA) under normal photopic lighting without glare conditions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phentolamine Ophthalmic Solution 0.75% 2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis
Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist | 244 |
| Phentolamine Ophthalmic Solution Vehicle 2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis
Phentolamine Ophthalmic Solution Vehicle: Phentolamine Ophthalmic Solution Vehicle | 124 |
| Total | 368 |
Baseline characteristics
| Characteristic | Phentolamine Ophthalmic Solution 0.75% | Total | Phentolamine Ophthalmic Solution Vehicle |
|---|---|---|---|
| Age, Continuous | 34.2 years STANDARD_DEVIATION 15.61 | 34.6 years STANDARD_DEVIATION 16.29 | 35.6 years STANDARD_DEVIATION 17.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 30 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 223 Participants | 338 Participants | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 31 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 59 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 179 Participants | 272 Participants | 93 Participants |
| Region of Enrollment United States | 244 participants | 368 participants | 124 participants |
| Sex: Female, Male Female | 152 Participants | 217 Participants | 65 Participants |
| Sex: Female, Male Male | 92 Participants | 151 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 244 | 0 / 124 |
| other Total, other adverse events | 43 / 244 | 0 / 124 |
| serious Total, serious adverse events | 0 / 244 | 0 / 124 |
Outcome results
Primary
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline
Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter
Time frame: 90 minutes
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | Returning to <= 0.2mm of Baseline | 142 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | Not returning to <= 0.2mm of Baseline | 102 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | Returning to <= 0.2mm of Baseline | 7 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | Not returning to <= 0.2mm of Baseline | 117 Participants |
Secondary
Change From Baseline in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Without Glare Conditions
Change from Baseline in best-corrected distance visual acuity (BCDVA) under normal photopic lighting without glare conditions
Time frame: 6 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Change From Baseline in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Without Glare Conditions | 0.3 letters | Standard Deviation 3.73 |
| Phentolamine Ophthalmic Solution Vehicle | Change From Baseline in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Without Glare Conditions | -0.2 letters | Standard Deviation 4.64 |
Secondary
Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline
Percentage of subjects' study eyes returning to less than or equal to 0.2 mm from baseline pupil diameter
Time frame: 30 minutes to 24 hours
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 30 minutes | Returning to <=0.2 mm of Baseline | 10 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 30 minutes | Not returning to <=0.2 mm of Baseline | 234 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 60 minutes | Returning to <=0.2 mm of Baseline | 103 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 60 minutes | Not returning to <=0.2 mm of Baseline | 141 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 90 minutes | Returning to <=0.2 mm of Baseline | 142 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 90 minutes | Not returning to <=0.2 mm of Baseline | 102 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 2 Hours | Returning to <=0.2 mm of Baseline | 162 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 2 Hours | Not returning to <=0.2 mm of Baseline | 82 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 3 Hours | Returning to <=0.2 mm of Baseline | 193 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 3 Hours | Not returning to <=0.2 mm of Baseline | 51 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 4 Hours | Returning to <=0.2 mm of Baseline | 210 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 4 Hours | Not returning to <=0.2 mm of Baseline | 34 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 6 Hours | Returning to <=0.2 mm of Baseline | 221 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 6 Hours | Not returning to <=0.2 mm of Baseline | 23 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 24 Hours | Returning to <=0.2 mm of Baseline | 218 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 24 Hours | Not returning to <=0.2 mm of Baseline | 26 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 24 Hours | Not returning to <=0.2 mm of Baseline | 35 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 30 minutes | Returning to <=0.2 mm of Baseline | 5 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 3 Hours | Returning to <=0.2 mm of Baseline | 17 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 30 minutes | Not returning to <=0.2 mm of Baseline | 119 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 6 Hours | Returning to <=0.2 mm of Baseline | 44 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 60 minutes | Returning to <=0.2 mm of Baseline | 3 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 3 Hours | Not returning to <=0.2 mm of Baseline | 107 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 60 minutes | Not returning to <=0.2 mm of Baseline | 121 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 24 Hours | Returning to <=0.2 mm of Baseline | 89 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 90 minutes | Returning to <=0.2 mm of Baseline | 7 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 4 Hours | Returning to <=0.2 mm of Baseline | 21 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 90 minutes | Not returning to <=0.2 mm of Baseline | 117 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 6 Hours | Not returning to <=0.2 mm of Baseline | 80 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 2 Hours | Returning to <=0.2 mm of Baseline | 9 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 4 Hours | Not returning to <=0.2 mm of Baseline | 103 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline | 2 Hours | Not returning to <=0.2 mm of Baseline | 115 Participants |
Secondary
Percent of Subjects With Unchanged Accommodation From Baseline
Percentage of subjects with unchanged accommodation from baseline (-1 hour)
Time frame: 90 minutes to 6 Hours
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects With Unchanged Accommodation From Baseline | 90 Minutes | Unchanged from Baseline | 155 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects With Unchanged Accommodation From Baseline | 90 Minutes | Changed from Baseline | 89 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects With Unchanged Accommodation From Baseline | 2 Hours | Unchanged from Baseline | 165 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects With Unchanged Accommodation From Baseline | 2 Hours | Changed from Baseline | 79 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects With Unchanged Accommodation From Baseline | 3 Hours | Unchanged from Baseline | 186 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects With Unchanged Accommodation From Baseline | 3 Hours | Changed from Baseline | 58 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects With Unchanged Accommodation From Baseline | 6 Hours | Unchanged from Baseline | 204 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Percent of Subjects With Unchanged Accommodation From Baseline | 6 Hours | Changed from Baseline | 40 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects With Unchanged Accommodation From Baseline | 6 Hours | Changed from Baseline | 38 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects With Unchanged Accommodation From Baseline | 90 Minutes | Unchanged from Baseline | 65 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects With Unchanged Accommodation From Baseline | 3 Hours | Unchanged from Baseline | 81 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects With Unchanged Accommodation From Baseline | 90 Minutes | Changed from Baseline | 59 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects With Unchanged Accommodation From Baseline | 6 Hours | Unchanged from Baseline | 86 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects With Unchanged Accommodation From Baseline | 2 Hours | Unchanged from Baseline | 66 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects With Unchanged Accommodation From Baseline | 3 Hours | Changed from Baseline | 43 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Percent of Subjects With Unchanged Accommodation From Baseline | 2 Hours | Changed from Baseline | 58 Participants |
Secondary
Pupil Diameter (Change From Max)
Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)
Time frame: 30 minutes to 24 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Pupil Diameter (Change From Max) | 3 Hours | -2.917 millimeters | Standard Deviation 1.1721 |
| Phentolamine Ophthalmic Solution 0.75% | Pupil Diameter (Change From Max) | 90 Minutes | -2.157 millimeters | Standard Deviation 1.1911 |
| Phentolamine Ophthalmic Solution 0.75% | Pupil Diameter (Change From Max) | 4 Hours | -3.078 millimeters | Standard Deviation 1.1578 |
| Phentolamine Ophthalmic Solution 0.75% | Pupil Diameter (Change From Max) | 30 Minutes | -0.109 millimeters | Standard Deviation 0.7104 |
| Phentolamine Ophthalmic Solution 0.75% | Pupil Diameter (Change From Max) | 6 Hours | -3.267 millimeters | Standard Deviation 1.2743 |
| Phentolamine Ophthalmic Solution 0.75% | Pupil Diameter (Change From Max) | 2 Hours | -2.478 millimeters | Standard Deviation 1.1453 |
| Phentolamine Ophthalmic Solution 0.75% | Pupil Diameter (Change From Max) | 24 Hours | -3.134 millimeters | Standard Deviation 1.3607 |
| Phentolamine Ophthalmic Solution 0.75% | Pupil Diameter (Change From Max) | 60 Minutes | -1.457 millimeters | Standard Deviation 1.0825 |
| Phentolamine Ophthalmic Solution Vehicle | Pupil Diameter (Change From Max) | 24 Hours | -2.313 millimeters | Standard Deviation 1.3607 |
| Phentolamine Ophthalmic Solution Vehicle | Pupil Diameter (Change From Max) | 30 Minutes | 0.092 millimeters | Standard Deviation 0.5335 |
| Phentolamine Ophthalmic Solution Vehicle | Pupil Diameter (Change From Max) | 90 Minutes | -0.284 millimeters | Standard Deviation 0.5852 |
| Phentolamine Ophthalmic Solution Vehicle | Pupil Diameter (Change From Max) | 2 Hours | -0.488 millimeters | Standard Deviation 0.6807 |
| Phentolamine Ophthalmic Solution Vehicle | Pupil Diameter (Change From Max) | 3 Hours | -0.987 millimeters | Standard Deviation 0.7932 |
| Phentolamine Ophthalmic Solution Vehicle | Pupil Diameter (Change From Max) | 4 Hours | -1.261 millimeters | Standard Deviation 0.8615 |
| Phentolamine Ophthalmic Solution Vehicle | Pupil Diameter (Change From Max) | 6 Hours | -1.755 millimeters | Standard Deviation 1.0205 |
| Phentolamine Ophthalmic Solution Vehicle | Pupil Diameter (Change From Max) | 60 Minutes | -0.059 millimeters | Standard Deviation 0.5775 |