Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis

Randomized, Parallel Arm, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Mydriasis; Dilation
• Intervention / Treatment: Drug: Phentolamine Ophthalmic Solution 0.75%; Other: Phentolamine Ophthalmic Solution Vehicle (Placebo)

Detailed Description

A randomized, parallel arm, double-masked, placebo-controlled Phase 3 study in at least 168 randomized subjects (160 completed), 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 1:1, Nyxol or placebo (vehicle).

Stratification by iris color will be 1:1, light or dark irides.

The mydriatic agent randomization will be 3:1:1 (2.5% phenylephrine, 1% tropicamide, and Paremyd). That is, approximately 60% of the randomized subjects will receive one drop of 2.5% phenylephrine 1 hour before treatment (96 completed subjects), approximately 20% will receive one drop of 1% tropicamide 1 hour before treatment (32 completed subjects), and approximately 20% will receive Paremyd 1 hour before treatment (32 completed subjects).

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.

At the Follow-Up Visit, which is 1 day after Visit 1, measurements will again be recorded 24 hours after treatment dosing.

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Clinical site 11
    • San Diego, California, United States, 92123
      • Clinical Site 10
  • Florida
    • Longwood, Florida, United States, 32779
      • Clinical Site 9
    • Orlando, Florida, United States, 32751
      • Clinical Site 6
  • Georgia
    • Roswell, Georgia, United States, 30075
      • Clinical Site 2
  • Kansas
    • Pittsburg, Kansas, United States, 66762
      • Clinical Site 7
    • Shawnee Mission, Kansas, United States, 66203
      • Clinical Site 3
  • Ohio
    • Athens, Ohio, United States, 45701
      • Clinical Site 5
    • Cincinnati, Ohio, United States, 45242
      • Clinical Site 12
    • Cleveland, Ohio, United States, 44195
      • Clinical Site 1
  • Rhode Island
    • Warwick, Rhode Island, United States, 02888
      • Clinical Site 8
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Site 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Males or females ≥ 12 years of age
2. Otherwise healthy and well controlled subjects

Exclusion Criteria:

Ophthalmic (in either eye):

1. Clinically significant ocular disease as deemed by the Investigator 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
6. Recent or current evidence of ocular infection or inflammation in either eye
7. History of diabetic retinopathy or diabetic macular edema
8. Closed or very narrow angles that in the Investigator's opinion are potentially occludable if the subject's pupil is dilated
9. History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris
10. Known allergy or contraindication to any component of the mydriatic agents or the vehicle formulation
11. History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal

Systemic:

1. Known hypersensitivity or contraindication to α- and/or β adrenoceptor antagonists.
2. Clinically significant systemic disease that might interfere with the study
3. 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
4. Participation in any investigational study within 30 days prior to screening
5. Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
6. Resting HR outside the normal range (50-110 beats per minute)
7. Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phentolamine Ophthalmic Solution 0.75%; 2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis	Drug: Phentolamine Ophthalmic Solution 0.75%; 0.75% phentolamine ophthalmic solution (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist; Other Names: Nyxol®; Nyxol
Placebo Comparator: Phentolamine Ophthalmic Solution Vehicle; 2 drops in study eye and 1 drop in non-study eye, 1 hour post pharmacologically-induced mydriasis	Other: Phentolamine Ophthalmic Solution Vehicle (Placebo); Topical sterile ophthalmic solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects' Study Eyes Pupil Diameter Returning to Baseline	Percentage of subjects' study eyesreturning to less than or equal to 0.2 mm from baseline pupil diameter	up to 24 hours
Pupil Diameter (Change From Max)	Change (mm) from maximum pharmacologically-induced mydriatic pupil diameter (0 minutes)	up to 24 hours
Percent of Subjects With Unchanged Accommodation From Baseline	Percentage of subjects with unchanged accommodation from baseline (-1 hour)	up to 6 hours

Collaborators and Investigators

• Sponsor: Ocuphire Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2020
• Primary Completion (Actual): December 23, 2020
• Study Completion (Actual): March 15, 2021

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 6, 2020

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: August 1, 2023

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-301 (MIRA-2)

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