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

• ClinicalTrials.gov Identifier: NCT04024891
• Recruitment Status: Completed
• First Posted: July 18, 2019
• Last Update Posted: October 14, 2019
• Sponsor: Ocuphire Pharma, Inc.
• Information provided by (Responsible Party): Ocuphire Pharma, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Mydriasis; Dilation	Drug: Phentolamine Mesylate Ophthalmic Solution 1%; Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 13, 2019
• Actual Primary Completion Date: September 17, 2019
• Actual Study Completion Date: September 17, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Pupil Diameter (Change from Max) [ Time Frame: 2 hours ]
   Change in pharmacologically-induced mydriatic (maximum) pupil diameter at 2 hours post-treatment in the study eye.

Secondary Outcome Measures :

1. Pupil Diameter (Change from Max) [ Time Frame: 30 min, 1 hours, 4 hours, 6 hours ]
   Change in pharmacologically-induced mydriatic (maximum) pupil diameter at remaining timepoints (30 min, 1 hours, 4 hours, 6 hours)
2. Accommodation Measured by the Near Point Rule (Diopters) (Change from Baseline) [ Time Frame: 0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours ]

   Change from baseline (-1 hour) in accommodation at each timepoint (0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours)

   Worsening of accommodation is defined as an amplitude decrease of greater than 1 diopter compared to baseline

3. Best Corrected Distance Visual Acuity (BCDVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Light Box Chart (Letters) at 4 Meters (Change from Baseline) [ Time Frame: 0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours ]
   Change from baseline (-1 hour) in BCDVA at each timepoint (0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours)
4. 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) [ Time Frame: 0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours ]
   Change from baseline (-1 hour) in DCNVA at each timepoint (0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours)
5. 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) (Change from Baseline) [ Time Frame: 0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours ]
   Change from baseline (-1 hour) in conjunctival hyperemia at each timepoint (0 min, 30 min, 1 hour, 2 hours, 4 hours, 6 hours), for study eye and non-study eye; in all subjects, in subjects taking Lumify®, and in subjects not taking Lumify®

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Kansas

Kannar Eye Care

Pittsburg, Kansas, United States, 66762

United States, Kentucky

Kentucky Eye Institute

Lexington, Kentucky, United States, 40517

United States, Ohio

Athens Eye Care

Athens, Ohio, United States, 45701

United States, Rhode Island

West Bay Eye Associates

Warwick, Rhode Island, United States, 02888

Sponsors and Collaborators

Ocuphire Pharma, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Ocuphire Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT04024891
• Other Study ID Numbers: OPI-NYXRM-201 (MIRA-1)
• First Posted: July 18, 2019
• Last Update Posted: October 14, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ocuphire Pharma, Inc.:

Nyxol; Pharmacologically Induced Mydriasis; Dilation

Additional relevant MeSH terms:

Mydriasis; Dilatation, Pathologic; Pathological Conditions, Anatomical; Pupil Disorders; Eye Diseases; Phentolamine; Pharmaceutical Solutions; Ophthalmic Solutions; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antihypertensive Agents