Study of the Safety, Efficacy and PK of EYN-1601 in Dilation of the Pupil
Primary Purpose
Mydriasis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
MDD-administered EYN-1601
Phenylephrine 2.5% Eyedrop
Phenylephrine 10% Eyedrop
Sponsored by
About this trial
This is an interventional treatment trial for Mydriasis
Eligibility Criteria
Inclusion Criteria:
- Female subjects must be 1-year postmenopausal, surgically sterilized, or women of childbearing potential with a negative urine pregnancy test at Visit 1.
- Provide signed written consent prior to participation in any study-related procedures
Exclusion Criteria:
- Pregnancy or lactation.
- History of diabetes.
- History of cardiac, renal, or hepatic impairment or disease.
- Allergy to phenylephrine hydrochloride.
- Allergy to benzalkonium chloride.
- History of closed-angle glaucoma.
- Anatomically narrow anterior chamber angles (or Shaffer gonioscopic grade of ≥ 2 in either eye).
- Hypertension or treatment for systemic hypertension.
- Ocular surgery or laser treatment of any kind in the study eye within 3 months.
- History of benign prostatic hyperplasia.
- History of chronic or acute uveitis.
- History of traumatic iritis or hyphema.
- History of traumatic mydriasis or angle recession.
- History of anxiety or panic disorders.
- History of thyrotoxicosis, hypothyroidism, or endocrine disease.
- Use of calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, benzodiazepines, monoamine oxidase inhibitors, tricyclic antidepressants, anticonvulsants, and systemic steroids (topical, inhaled, intranasal, or perianal steroids are permitted) during the study period.
- Participation in any study of an investigational product or device within 30 days prior to Screening or at any time during the study period.
- Irregularly-shaped pupil secondary to ocular trauma, intraocular surgery or congenital defect.
- History of neurogenic pupil disorder (eg, Horner's syndrome, third cranial nerve palsy, Adie's pupil, Argyl Robertson syndrome, etc.).
- History of anterior chamber intraocular lens (IOL) or iris-fixated IOL.
- History of iris surgery of any kind (eg, iridotomy, iridectomy, coreoplasty)
- History of iris atrophy
- Unwilling to discontinue use of contact lenses on the day of a treatment visit.
- Current active eye disease other than dry eye disease (ie, any disease for which topical or systemic ophthalmic medication is necessary).
- Use of any ophthalmic medication except unpreserved artificial tears on the day of a treatment visit.
- Has a severe/serious ocular condition, or any other unstable medical condition that, in the Investigator's opinion, may preclude study treatment or follow-up.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
MDD-administered EYN-1601
Phenylephrine 2.5% Eyedrop
Phenylephrine 10% Eyedrop
Arm Description
EYN-1601 Ophthalmic Solution administered using the Eyenovia MDD
Phenylephrine Hydrochloride Ophthalmic Solution 2.5% administered as an eyedrop
Phenylephrine Hydrochloride Ophthalmic Solution 10% administered as an eyedrop
Outcomes
Primary Outcome Measures
Pupil Dilation
Mean change in pupil diameter from baseline (prior to study drug administration)
Secondary Outcome Measures
Blood Pressure
Mean change in blood pressure from baseline (prior to study drug administration)
Heart Rate
Mean change in heart rate from baseline (prior to study drug administration)
PK (Concentration of free phenylephrine in the blood plasma)
Concentration of free phenylephrine in the blood plasma
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02946125
Brief Title
Study of the Safety, Efficacy and PK of EYN-1601 in Dilation of the Pupil
Official Title
A Single-Center, Open-Label, Observer-Masked, Active-Controlled, Phase 2 Study of the Safety, Efficacy and Pharmacokinetics of EYN-1601 in Dilation of the Pupil
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
October 2016 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eyenovia Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 2 study to investigate the safety, efficacy and pharmacokinetics of EYN-1601 for dilation of the pupil. A single microdose of EYN-1601 will be compared to single doses of commercially available phenylephrine hydrochloride 2.5% and 10% ophthalmic solutions.
Detailed Description
EYN-1601 delivered topically as a microdose via a proprietary delivery system (the Eyenovia Multi-Dose Device [MDD] system) is being investigated for dilation of the pupil for ophthalmic examinations and procedures. Phenylephrine hydrochloride, a sympathetic α1-adrenergic agonist, has been used for pupil dilation for over 70 years. The mydriatic action of phenylephrine is due to its stimulation of the α1 receptors of the radial muscle of the iris, which causes the muscle fibers to contract and results in pupil dilation.
When conducting a variety of ophthalmological procedures, it is necessary to dilate (enlarge) the pupil to allow an unobstructed view of the lens and retina, as well as the optic nerve. The degree of pupil dilation required is somewhat dependent on the procedure being performed. Eyenovia, the Sponsor, is a specialty pharmaceutical company focused on the development of ophthalmic drug products that can be delivered in small volumes, ie, via microdosing, in order to maximize therapeutic control and minimize systemic absorption. To achieve this goal, Eyenovia is developing a drug/device combination product to allow accurate topical ocular delivery of controlled quantities of specific active pharmaceutical ingredients.
Phenylephrine has been known to cause systemic cardiovascular effects in some patients when dosed via the topical ocular route including hypertension, tachycardia, and more rarely, arrhythmia and stroke, especially in those patients with pre-existing heart conditions. These risks are even more relevant when phenylephrine hydrochloride ophthalmic solution 10% is used in circumstances where a greater degree of mydriasis is required. Microdosing with the Eyenovia MDD system is expected to significantly reduce or eliminate these risks while allowing the same degree of mydriasis produced with the currently approved products.
Subjects (healthy volunteers) will be screened for eligibility and 12 subjects that meet inclusion/exclusion criteria will be enrolled into the study. All subjects will be followed through the same pre-specified treatment visit schedule at which the 3 study drugs are administered (phenylephrine 2.5% eyedrops at Visit 1, phenylephrine 10% eyedrops at Visit 2 and EYN-1601 MDD at Visit 3). At each treatment visit, baseline measurements will be taken prior to study medication administration.
Subjects will participate in safety, efficacy, and pharmacokinetic assessments. Subsequent visits must be separated by at least 2 days but may be up to 1 week apart.
Efficacy will be assessed by measurement of pupil dilation in both eyes.
Safety assessments will include slit lamp examination (SLE) of both eyes and measurement of vital signs (blood pressure [BP]/heart rate [HR]) and adverse events, as well as an ocular discomfort survey
Absorption will be assessed through blood plasma analysis to detect free phenylephrine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mydriasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MDD-administered EYN-1601
Arm Type
Experimental
Arm Description
EYN-1601 Ophthalmic Solution administered using the Eyenovia MDD
Arm Title
Phenylephrine 2.5% Eyedrop
Arm Type
Active Comparator
Arm Description
Phenylephrine Hydrochloride Ophthalmic Solution 2.5% administered as an eyedrop
Arm Title
Phenylephrine 10% Eyedrop
Arm Type
Active Comparator
Arm Description
Phenylephrine Hydrochloride Ophthalmic Solution 10% administered as an eyedrop
Intervention Type
Combination Product
Intervention Name(s)
MDD-administered EYN-1601
Other Intervention Name(s)
MiDD-administered phenylephrine hydrochloride 10%
Intervention Description
Phenylephrine hydrochloride ophthalmic solution 10% formulated for microdose spray delivery
Intervention Type
Drug
Intervention Name(s)
Phenylephrine 2.5% Eyedrop
Intervention Description
Phenylephrine hydrochloride ophthalmic solution 2.5% eyedrop
Intervention Type
Drug
Intervention Name(s)
Phenylephrine 10% Eyedrop
Intervention Description
Phenylephrine hydrochloride ophthalmic solution 10% eyedrop
Primary Outcome Measure Information:
Title
Pupil Dilation
Description
Mean change in pupil diameter from baseline (prior to study drug administration)
Time Frame
15, 30, 45, 60, 75, 120 and 180 minutes post administration of study drug
Secondary Outcome Measure Information:
Title
Blood Pressure
Description
Mean change in blood pressure from baseline (prior to study drug administration)
Time Frame
10, 15, 30, 45 and 60 minutes post administration of study drug
Title
Heart Rate
Description
Mean change in heart rate from baseline (prior to study drug administration)
Time Frame
10, 15, 30, 45 and 60 minutes post administration of study drug
Title
PK (Concentration of free phenylephrine in the blood plasma)
Description
Concentration of free phenylephrine in the blood plasma
Time Frame
20 minutes post administration of study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Female subjects must be 1-year postmenopausal, surgically sterilized, or women of childbearing potential with a negative urine pregnancy test at Visit 1.
Provide signed written consent prior to participation in any study-related procedures
Exclusion Criteria:
Pregnancy or lactation.
History of diabetes.
History of cardiac, renal, or hepatic impairment or disease.
Allergy to phenylephrine hydrochloride.
Allergy to benzalkonium chloride.
History of closed-angle glaucoma.
Anatomically narrow anterior chamber angles (or Shaffer gonioscopic grade of ≥ 2 in either eye).
Hypertension or treatment for systemic hypertension.
Ocular surgery or laser treatment of any kind in the study eye within 3 months.
History of benign prostatic hyperplasia.
History of chronic or acute uveitis.
History of traumatic iritis or hyphema.
History of traumatic mydriasis or angle recession.
History of anxiety or panic disorders.
History of thyrotoxicosis, hypothyroidism, or endocrine disease.
Use of calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, benzodiazepines, monoamine oxidase inhibitors, tricyclic antidepressants, anticonvulsants, and systemic steroids (topical, inhaled, intranasal, or perianal steroids are permitted) during the study period.
Participation in any study of an investigational product or device within 30 days prior to Screening or at any time during the study period.
Irregularly-shaped pupil secondary to ocular trauma, intraocular surgery or congenital defect.
History of neurogenic pupil disorder (eg, Horner's syndrome, third cranial nerve palsy, Adie's pupil, Argyl Robertson syndrome, etc.).
History of anterior chamber intraocular lens (IOL) or iris-fixated IOL.
History of iris surgery of any kind (eg, iridotomy, iridectomy, coreoplasty)
History of iris atrophy
Unwilling to discontinue use of contact lenses on the day of a treatment visit.
Current active eye disease other than dry eye disease (ie, any disease for which topical or systemic ophthalmic medication is necessary).
Use of any ophthalmic medication except unpreserved artificial tears on the day of a treatment visit.
Has a severe/serious ocular condition, or any other unstable medical condition that, in the Investigator's opinion, may preclude study treatment or follow-up.
Facility Information:
City
Artesia
State/Province
California
ZIP/Postal Code
90701
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Study of the Safety, Efficacy and PK of EYN-1601 in Dilation of the Pupil
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