Dilation, Mydriasis
Conditions
Keywords
Nyxol, Pharmacologically Induced Mydriasis, Dilation, Pediatrics, Phentolamine, Mydriasis, Phenylephrine, Tropicamide, Paremyd
Brief summary
The objectives of this study are: * To evaluate the safety of Nyxol in pediatric subjects * To evaluate the efficacy of Nyxol to expedite the reversal of pharmacologically induced mydriasis in pediatric subjects The Sponsor intends to use this study to evaluate Nyxol in pediatric subjects aged 3 to 11 for the indication the treatment of pharmacologically induced mydriasis produced by adrenergic (phenylephrine) or parasympatholytic (tropicamide) agents, or a combination thereof.
Detailed description
This is a randomized, parallel-arm, double-masked, placebo-controlled study in approximately 20 randomized pediatric subjects evaluating the safety and efficacy of Nyxol in pediatric subjects with pharmacologically induced mydriasis with three dilating agents (e.g., phenylephrine, tropicamide, and Paremyd). Pediatric subjects will be recruited for the study into 2 age groups as follows:1) 3 to 5 years of age: 10 subjects 2) 6 to 11 years of age: 10 subjects.
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
3 Years to 11 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males or premenstrual females 3 to 11 years of age 2. Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits 3. Parent/Legal guardian willing to give written informed consent to participate in this study. Children aged 7 to 11 years to provide signed assent form, as well as a separate parental/legal guardian consent.
Exclusion criteria
1. Clinically significant ocular disease as deemed by the Investigator(eg, amblyopia, congenital cataract, congenital glaucoma) 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 or ocular surgery 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 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. History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris 9. Known allergy, hypersensitivity, or contraindication to any component of the phentolamine ophthalmic solution or to any component of the mydriatic agents or vehicle formulation Systemic: 10. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists 11. Clinically significant systemic disease (eg, uncontrolled diabetes, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that in the opinion of the Investigator could interfere with the study 12. Subjects with learning disabilities that in the opinion of the investigator could interfere with the study 13. 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(Appendix 4) 14. Participation in any investigational study within 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Measurements | 0 Minutes, 90 Minutes, 3 Hours, 24 Hours | Study Eye Change from Baseline (-1 Hour) Conjunctival Hyperemia Grading; Cornea and Contact Lens Research Unit (CCLRU scale) Grades range from 0 to 3, with 3 being considered the most severe. |
| Vital Signs | 3 Hours, 24 Hours | Change from Screening Heart Rate |
| Safety Measurement | 0 Minutes, 3 Hours, 24 Hours | Study Eye Change from Baseline (-1 Hour) in Best Corrected Distance Visual Acuity |
| Change From Screening Blood Pressure (Diastolic) | 3 Hours, 24 Hours | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Measurement: Pupil Diameter | 90 Minutes, 3 Hours, and 24 Hours | Percentage of Subjects Returning to ≤ 0.2 mm from Baseline (-1 hour) Pupil Diameter (Study Eye) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phentolamine Ophthalmic Solution 0.75% One drop of study medication in each eye.
Phentolamine Ophthalmic Solution 0.75%: 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist | 11 |
| Phentolamine Ophthalmic Solution Vehicle One drop of study medication in each eye.
Phentolamine Ophthalmic Solution Vehicle: Phentolamine Ophthalmic Solution Vehicle | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Phentolamine Ophthalmic Solution 0.75% | Phentolamine Ophthalmic Solution Vehicle | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 12 Participants | 23 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.9 years STANDARD_DEVIATION 2.74 | 5.8 years STANDARD_DEVIATION 2.66 | 6.3 years STANDARD_DEVIATION 2.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 11 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 10 Participants | 21 Participants |
| Region of Enrollment United States | 11 participants | 12 participants | 23 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 0 / 11 | 0 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Change From Screening Blood Pressure (Diastolic)
Time frame: 3 Hours, 24 Hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Change From Screening Blood Pressure (Diastolic) | 3 Hours | -2.4 mmHg | Standard Deviation 9.72 |
| Phentolamine Ophthalmic Solution 0.75% | Change From Screening Blood Pressure (Diastolic) | 24 Hours | -1.1 mmHg | Standard Deviation 11.63 |
| Phentolamine Ophthalmic Solution Vehicle | Change From Screening Blood Pressure (Diastolic) | 3 Hours | 1.0 mmHg | Standard Deviation 15.68 |
| Phentolamine Ophthalmic Solution Vehicle | Change From Screening Blood Pressure (Diastolic) | 24 Hours | -3.8 mmHg | Standard Deviation 7.96 |
Primary
Safety Measurement
Study Eye Change from Baseline (-1 Hour) in Best Corrected Distance Visual Acuity
Time frame: 0 Minutes, 3 Hours, 24 Hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Safety Measurement | 0 Minutes | -1.2 letters | Standard Deviation 1.66 |
| Phentolamine Ophthalmic Solution 0.75% | Safety Measurement | 3 Hours | 1.2 letters | Standard Deviation 1.89 |
| Phentolamine Ophthalmic Solution 0.75% | Safety Measurement | 24 Hours | 1.5 letters | Standard Deviation 1.97 |
| Phentolamine Ophthalmic Solution Vehicle | Safety Measurement | 0 Minutes | -0.3 letters | Standard Deviation 1.23 |
| Phentolamine Ophthalmic Solution Vehicle | Safety Measurement | 3 Hours | 0.1 letters | Standard Deviation 0.67 |
| Phentolamine Ophthalmic Solution Vehicle | Safety Measurement | 24 Hours | 0.7 letters | Standard Deviation 1.15 |
Primary
Safety Measurements
Study Eye Change from Baseline (-1 Hour) Conjunctival Hyperemia Grading; Cornea and Contact Lens Research Unit (CCLRU scale) Grades range from 0 to 3, with 3 being considered the most severe.
Time frame: 0 Minutes, 90 Minutes, 3 Hours, 24 Hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Safety Measurements | 0 Minutes | 0.3 score on a scale | Standard Deviation 0.65 |
| Phentolamine Ophthalmic Solution 0.75% | Safety Measurements | 90 Minutes | 1.6 score on a scale | Standard Deviation 0.5 |
| Phentolamine Ophthalmic Solution 0.75% | Safety Measurements | 3 Hours | 1.1 score on a scale | Standard Deviation 0.54 |
| Phentolamine Ophthalmic Solution 0.75% | Safety Measurements | 24 Hours | 0.1 score on a scale | Standard Deviation 0.3 |
| Phentolamine Ophthalmic Solution Vehicle | Safety Measurements | 24 Hours | -0.2 score on a scale | Standard Deviation 0.58 |
| Phentolamine Ophthalmic Solution Vehicle | Safety Measurements | 0 Minutes | -0.2 score on a scale | Standard Deviation 0.58 |
| Phentolamine Ophthalmic Solution Vehicle | Safety Measurements | 3 Hours | -0.1 score on a scale | Standard Deviation 0.29 |
| Phentolamine Ophthalmic Solution Vehicle | Safety Measurements | 90 Minutes | 0.0 score on a scale | Standard Deviation 0.43 |
Primary
Vital Signs
Change from Screening Blood Pressure (Systolic)
Time frame: 3 Hours, 24 Hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Vital Signs | 3 Hours | -4.6 mmHg | Standard Deviation 8.91 |
| Phentolamine Ophthalmic Solution 0.75% | Vital Signs | 24 Hours | -2.8 mmHg | Standard Deviation 7.48 |
| Phentolamine Ophthalmic Solution Vehicle | Vital Signs | 3 Hours | -0.8 mmHg | Standard Deviation 12.39 |
| Phentolamine Ophthalmic Solution Vehicle | Vital Signs | 24 Hours | -5.8 mmHg | Standard Deviation 6.98 |
Primary
Vital Signs
Change from Screening Heart Rate
Time frame: 3 Hours, 24 Hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Vital Signs | 3 Hours | -1.1 beats per minute | Standard Deviation 7.92 |
| Phentolamine Ophthalmic Solution 0.75% | Vital Signs | 24 Hours | -2.5 beats per minute | Standard Deviation 10.1 |
| Phentolamine Ophthalmic Solution Vehicle | Vital Signs | 3 Hours | -2.0 beats per minute | Standard Deviation 14.24 |
| Phentolamine Ophthalmic Solution Vehicle | Vital Signs | 24 Hours | -3.5 beats per minute | Standard Deviation 12.69 |
Secondary
Efficacy Measurement: Pupil Diameter
Percentage of Subjects Returning to ≤ 0.2 mm from Baseline (-1 hour) Pupil Diameter (Study Eye)
Time frame: 90 Minutes, 3 Hours, and 24 Hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Efficacy Measurement: Pupil Diameter | 90 Minutes | 7 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Efficacy Measurement: Pupil Diameter | 3 Hours | 9 Participants |
| Phentolamine Ophthalmic Solution 0.75% | Efficacy Measurement: Pupil Diameter | 24 Hours | 10 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Efficacy Measurement: Pupil Diameter | 90 Minutes | 3 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Efficacy Measurement: Pupil Diameter | 3 Hours | 4 Participants |
| Phentolamine Ophthalmic Solution Vehicle | Efficacy Measurement: Pupil Diameter | 24 Hours | 6 Participants |
Secondary
Efficacy Measurement: Pupil Diameter
Change (in mm) in Pupil Diameter from Max Pupil Dilation (0 minutes) (Study Eye)
Time frame: 90 Minutes, 3 Hours, and 24 Hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Efficacy Measurement: Pupil Diameter | 90 Minutes | -1.475 millimeters | Standard Deviation 0.7188 |
| Phentolamine Ophthalmic Solution 0.75% | Efficacy Measurement: Pupil Diameter | 3 Hours | -2.031 millimeters | Standard Deviation 0.6919 |
| Phentolamine Ophthalmic Solution 0.75% | Efficacy Measurement: Pupil Diameter | 24 Hours | -2.005 millimeters | Standard Deviation 1.2841 |
| Phentolamine Ophthalmic Solution Vehicle | Efficacy Measurement: Pupil Diameter | 90 Minutes | -0.378 millimeters | Standard Deviation 0.4473 |
| Phentolamine Ophthalmic Solution Vehicle | Efficacy Measurement: Pupil Diameter | 3 Hours | -0.723 millimeters | Standard Deviation 0.647 |
| Phentolamine Ophthalmic Solution Vehicle | Efficacy Measurement: Pupil Diameter | 24 Hours | -1.44 millimeters | Standard Deviation 1.2891 |
Secondary
Efficacy Measurement: Pupil Diameter
Time (Hours) to Return to ≤ 0.2 mm from Baseline (-1 Hour) Pupil Diameter (Time-savings Analysis) (Study Eye)
Time frame: Up to 24 Hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phentolamine Ophthalmic Solution 0.75% | Efficacy Measurement: Pupil Diameter | 2.95 hours | Standard Deviation 2.564 |
| Phentolamine Ophthalmic Solution Vehicle | Efficacy Measurement: Pupil Diameter | 5.54 hours | Standard Deviation 3.078 |