Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) in Subjects With Dim Light Vision Disturbances

Randomized, Placebo-Controlled, Double-Masked Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) in Subjects With Dim Light Vision Disturbances

The objectives of this study are:

• To evaluate the efficacy of Nyxol to improve mesopic low contrast visual acuity (mLCVA) in subjects with Dim Light Vision Disturbances (DLD)
• To evaluate efficacy of Nyxol to improve visual performance
• To evaluate the safety of Nyxol

Study Overview

• Status: Completed
• Conditions: Dim Light Vision Disturbances
• Intervention / Treatment: Drug: Phentolamine Ophthalmic Solution 0.75%; Drug: Phentolamine Ophthalmic Solution Vehicle (Placebo)

Detailed Description

Placebo-controlled, double-masked, multiple-dose, Phase 3 study in approximately 160 randomized subjects with DLD (approximately 136 that are evaluable for efficacy), evaluating safety and efficacy of Nyxol in subjects with DLD following administration of Nyxol once daily (QD) at or near bedtime (at 8PM to 10PM) in both eyes (OU) for 14 days.

Following the successful completion of screening, each subject will be stratified by iris color (light/dark irides) and will then be randomized to treatment (masked) 1:1, Nyxol or placebo (vehicle).

Treatment (Nyxol or placebo) will be administered in both eyes (OU) by the subjects at or near bedtime each day.

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

Treatment visits will occur 2 times: Day 8 (+1 day)/Visit 2 and Day 15 (+1 day)/Visit 3. mLCVA evaluations shall be performed on each of these days.

A follow-up visit (Visit 4) phone call will occur 1 to 3 days after Visit 3.

At select sites OPD Scan measurements will be made using wavefront abhermettry.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Clinical Site 6
    • Petaluma, California, United States, 94954
      • Clinical Site 1
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Clinical Site 3
    • Jacksonville, Florida, United States, 32256
      • Clinical Site 18
  • Kansas
    • Pittsburg, Kansas, United States, 66762
      • Clinical Site 13
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Clinical Site 20
    • Louisville, Kentucky, United States, 41008
      • Clinical Site 14
  • New Jersey
    • Palisades Park, New Jersey, United States, 07650
      • Clinical Site 10
    • Pennington, New Jersey, United States, 08534
      • Clinical Site 8
  • North Carolina
    • Elizabeth City, North Carolina, United States, 27909
      • Clinical Site 4
    • High Point, North Carolina, United States, 27262
      • Clinical Site 22
    • High Point, North Carolina, United States, 27262
      • Clinical Site 9
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Clinical Site 2
  • Rhode Island
    • Warwick, Rhode Island, United States, 57108
      • Clinical Test 15
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical site 11
  • Texas
    • San Antonio, Texas, United States, 78240
      • Clinical Site 5
  • Utah
    • Ogden, Utah, United States, 84403
      • Clinical Site 19

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females ≥ 18 years of age
2. Subject-reported DLD (likely subjects with a history of multifocal IOLs, post-laser-assisted in situ keratomileusis [LASIK], corneal scars, and keratoconus)
3. Ability to comply with all protocol-mandated procedures independently and to attend all
4. Otherwise healthy and well-controlled subjects
5. Able and willing to give written consent to participate in this study
6. Able to self-administer study medication
7. PD ≥ 6 mm under mesopic conditions (prior to illumination) in at least one eye
8. ≤ 20 (20/100 Snellen or worse) ETDRS letters in mLCVA score

Exclusion Criteria:

Ophthalmic:

1. Prior history of dry eye diagnosis, taking prescription drops for dry eye, or taking artificial tear drops occasionally for dry eye
2. Prior history of fluctuating vision
3. Clinically significant ocular disease as deemed by the Investigator that might interfere with the study
4. Known hypersensitivity to any topical alpha-adrenoceptor antagonists
5. Known allergy or contraindication to any component of the vehicle formulation
6. History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal
7. Ocular trauma, ocular surgery (e.g., IOLs) or laser procedure (e.g., LASIK, photorefractive keratectomy [PRK]) within 6 months prior to screening
8. Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of screening
9. Recent or current evidence of ocular infection or inflammation in either eye. Subjects must be symptom free for at least 7 days.
10. History of diabetic retinopathy, diabetic macular edema, or dry or wet macular degeneration
11. History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris
12. Unwilling or unable to discontinue use of contact lenses at screening until study completion, except for keratoconus subjects who may wear contacts up to 24 hours prior to their scheduled visits

Systemic:

1. Known hypersensitivity or contraindication to alpha- and/or beta-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 and during the conduct of the study
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 specified 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%; One drop in both eyes at or near bedtime (8PM to 10PM)	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; One drop in both eyes at or near bedtime (8PM to 10PM)	Drug: 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 With 3 Lines mLCVA Improvement in Study Eye	Percent of subjects with ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (≥3 lines) of improvement in the study eye compared to baseline in monocular mLCVA at Day 8	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects With mLCVA Improvement in Study Eye	Percent of subjects with ≥ 5, ≥ 10, and ≥ 15 ETDRS letters (≥ 1, ≥ 2, and ≥ 3 lines, respectively) improvement compared to baseline in mLCVA at Day 8 (excluding the primary endpoint)	up to 15 days
Percent of Subjects With Photopic Low Contrast Visual Acuity (pLCVA) and mHCVA Improvement in Study Eye	Percent of subjects with ≥ 5, ≥ 10, and ≥ 15 ETDRS letters (≥ 1, ≥ 2, and ≥ 3 lines, respectively) improvement compared to baseline in pLCVA and mHCVA at Day 8 and Day 15	up to 15 days
Change From Baseline in Study Eye Mesopic Pupil Diameter (PD)	Change from baseline in study eye mesopic PD	up to 15 days
Percent Change From Baseline in Study Eye Mesopic Pupil Diameter (PD)	Percent change from baseline in study eye mesopic PD	up to 15 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change and percent change in total RMS error and higher-order RMS	Change and percent change from baseline in total RMS error (score) and higher-order RMS (spherical, coma, trefoil) error under mesopic conditions	up to 15 days

Collaborators and Investigators

• Sponsor: Ocuphire Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): May 19, 2022
• Study Completion (Actual): May 19, 2022

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 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, Night Vision Disturbances, Glare, Halos, Starbursts
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Sensation Disorders; Vision Disorders; 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-NYXDLD-301 (LYNX-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