Safety and Efficacy of Ophthalmic Phentolamine Mesylate to Reverse Pharmacologically Induced Mydriasis

Randomized, Cross-Over, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Phentolamine Mesylate Ophthalmic Solution to Reverse Pharmacologically Induced Mydriasis in Normal Healthy Subjects

The objectives of this study are:

• To evaluate the efficacy of Nyxol (phentolamine mesylate ophthalmic solution 1%) to expedite the reversal of pharmacologic mydriasis
• To evaluate the safety of Nyxol
• To evaluate the effect of Lumify® to suppress conjunctival hyperemia (redness) potentially associated with administration of Nyxol

Study Overview

• Status: Completed
• Conditions: Mydriasis; Dilation
• Intervention / Treatment: Drug: Phentolamine Mesylate Ophthalmic Solution 1%; Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo)

Detailed Description

Randomized, 2-arm cross-over, double-masked Phase 2b study in approximately 32 healthy subjects, evaluating safety and efficacy of Nyxol in subjects with pharmacologically induced mydriasis.

At the first visit subjects will be screened for study eligibility.

After screening, eligible subjects will be randomized 1:1 to one of the two treatment sequences:

Treatment sequence 1: Placebo (Visit 1), Nyxol (Visit 2).

Treatment sequence 2: Nyxol (Visit 1), Placebo (Visit 2).

Randomization will be stratified by mydriatic agent (2.5% phenylephrine or 1% tropicamide). Approximately one half of the randomized subjects will receive 2.5% phenylephrine and one half will receive 1% tropicamide. Subjects will receive their mydriatic agent 1 hour before treatment. Each subject will receive the same mydriatic agent throughout the study.

At each visit, pupil diameter (PD), accommodation, near and distance visual acuity (VA) and redness in each eye will be measured before (-1 hour/baseline) and 1 hour after (maximum/0 minutes) the mydriatic agent instillation in each eye (i.e., right before the study treatment is administered), and at 30 minutes, 1 hour, 2 hours, 4 hours and 6 hours after treatment dosing.

As needed, two hours post treatment, subjects may request the administration of Lumify® in the non-study eye.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Pittsburg, Kansas, United States, 66762
      • Kannar Eye Care
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Kentucky Eye Institute
  • Ohio
    • Athens, Ohio, United States, 45701
      • Athens Eye Care
  • Rhode Island
    • Warwick, Rhode Island, United States, 02888
      • West Bay Eye Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Males or females ≥ 18 and ≤ 45 years of age with brown irides (irises) only
2. Otherwise healthy and well controlled subjects
3. Able to comply with all protocol mandated procedures and to attend all scheduled office visits
4. Willing to give written informed consent to participate in this study

Exclusion Criteria

1. Clinically significant ocular disease as deemed by the Investigator (e.g., cataract, glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca) that might interfere with the study
2. Unwilling or unable to discontinue use of contact lenses during treatment visits
3. Ocular trauma, ocular surgery or non-refractive laser treatment within the 6 months prior to screening
4. Ocular medication of any kind within 30 days of screening, with the exception of a) lid scrubs (which may have been used prior to, but not after screening) or b) lubricating drops for dry eye (preservative-free artificial tears), which may be used in between the study treatment days
5. Recent or current evidence of ocular infection or inflammation. Current evidence of clinically significant blepharitis, conjunctivitis, or a history of herpes simplex or herpes zoster keratitis at screening
6. History of diabetic retinopathy
7. Closed or very narrow angles that in the Investigator's opinion are 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 (e.g., irregularly shaped pupil, neurogenic pupil disorder, iris atrophy, iridotomy)
9. Known allergy or contraindication to any component of the mydriatic agents or the vehicle formulation
10. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists (e.g., chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood pressure (BP) or heart rate (HR); second- or third-degree heart blockage or Congestive Heart Failure (CHF); severe diabetes)
11. Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine or cardiovascular disorders) that might interfere with the study
12. Initiation of treatment with or any changes to the current dosage, drug or regimen of any topical or systemic adrenergic or cholinergic drugs up to 7 days prior to screening, or during the study
13. Participation in any investigational study within 30 days prior to screening
14. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control. Acceptable methods include the use of at least one of the following: intrauterine device (IUD), hormonal (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence. An adult woman is considered to be of childbearing potential unless she is 1 year postmenopausal or 3 months post-surgical sterilization. All females of childbearing potential must have a negative urine pregnancy test result at Visit 1/Screening and Visit 2 examinations and must intend to not become pregnant during the study
15. Resting heart rate (HR) outside the normal range (50-110 beats per minute) at the Screening Visit. HR may be repeated only once if outside the normal range following at least a 5-minute rest period in the sitting position
16. Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg at the Screening Visit. BP may be repeated only once if outside the specified range following at least a 5-minute rest period in the sitting position

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phentolamine Mesylate Ophthalmic Solution 1%; 1 drop in each eye, 1 hour post medically-induced mydriasis	Drug: Phentolamine Mesylate Ophthalmic Solution 1%; 1% phentolamine mesylate ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist; Other Names: Nyxol®; Nyxol
Placebo Comparator: Phentolamine Mesylate Ophthalmic Solution Vehicle; 1 drop in each eye, 1 hour post medically-induced mydriasis	Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo); Topical Sterile Ophthalmic Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pupil Diameter (Change From Max)	Change in pharmacologically-induced mydriatic (maximum) pupil diameter at 2 hours post-treatment in the study eye.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pupil Diameter (Change From Max)	Change in pharmacologically-induced mydriatic (maximum) pupil diameter at remaining timepoints (30 min, 1 hours, 4 hours, 6 hours)	30 min, 1 hours, 4 hours, 6 hours
Pupil Diameter Return to Baseline	Percent of Subjects Achieving Pupil Diameter No More Than 0.5 mm Above Baseline by Time Point with either phenylephrine or tropicamide	0 min, 1 hour, 2 hours, 4 hours, 6 hours
Accommodation Measured by the Near Point Rule (Diopters) (Change From Baseline), Percent With Unchanged Accommodation	Change from baseline (-1 hour) in accommodation at each time point (0 min, 2 hours, 4 hours) with Tropicamide and Phenylephrine Worsening of accommodation is defined as an amplitude decrease of greater than 1 diopter compared to baseline	0 min, 2 hours, 4 hours
Conjunctival Hyperemia (Eye Redness) Assessed Visually With the Brien Holden Vision Institute (Formerly Corneal and Contact Lens Research Unit, or CCLRU) Bulbar Redness Scale (0-3)	Conjunctival hyperemia at each timepoint (0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours), for study eye; in all subjects. Scale 0-3 (None, Mild, Moderate, Severe)	0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours
Best Corrected Distance Visual Acuity (BCDVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Light Box Chart (Letters) at 4 Meters (Change From Baseline)	Change from baseline (-1 hour) in Best Corrected Distance Visual Acuity at each time point (0 min, 30 mins, 1 hour, 2 hours, 6 hours) in Study Eye	0 mins, 30 mins, 1 hour, 2 hours, 4 hours, 6 hours
Distance-Corrected Near Visual Acuity (DCNVA) Measured by Standard Reading Card (Original Series Sloan Letter ETDRS Card at 16 Inches, LogMAR Units) (Change From Baseline)	Change from baseline (-1 hour) in Distance Corrected Near Visual Acuity at each time point (0 min, 30 mins, 1 hour, 2 hours, 6 hours) in Study Eye	0 mins, 30 mins, 1 hour, 2 hours, 4 hours, 6 hours

Collaborators and Investigators

• Sponsor: Ocuphire Pharma, Inc.

Publications and helpful links

General Publications

• Karpecki PM, Foster SA, Montaquila SM, Kannarr SR, Slonim CB, Meyer AR, Sooch MP, Jaber RM, Charizanis K, Yousif JE, Klapman SA, Amin AT, McDonald MB, Horn GD, Lazar ES, Pepose JS. Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial. Optom Vis Sci. 2021 Mar 1;98(3):234-242. doi: 10.1097/OPX.0000000000001656.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2019
• Primary Completion (Actual): September 17, 2019
• Study Completion (Actual): September 17, 2019

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 18, 2019

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Nyxol; Pharmacologically Induced Mydriasis; Dilation
• Additional Relevant MeSH Terms: Eye Diseases; Pathological Conditions, Anatomical; Pupil Disorders; Dilatation, Pathologic; Mydriasis; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-Antagonists; Ophthalmic Solutions; Pharmaceutical Solutions; Phentolamine
• Other Study ID Numbers: OPI-NYXRM-201 (MIRA-1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No