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

Phase 3

Completed

• Conditions: Dim Light Vision Disturbances
• Interventions: Drug: Phentolamine Ophthalmic Solution Vehicle (Placebo); Drug: Phentolamine Ophthalmic Solution 0.75%

• Registration Number: NCT04638660
• Lead Sponsor: Ocuphire Pharma, Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-11-16
• Study First Submitted QC: 2020-11-16
• Study First Posted: 2020-11-20
• Study Start: 2020-12-30
• Primary Completion: 2022-05-19
• Study Completion: 2022-05-19
• Results First Submitted: 2023-07-06
• Status Verified: 2023-08
• Results First Submitted QC: 2023-08-08
• Results First Posted: 2023-08-09
• Last Update Submitted: 2023-08-15
• Last Update Posted: 2023-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 144

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phentolamine Ophthalmic Solution Vehicle	Phentolamine Ophthalmic Solution Vehicle (Placebo)	One drop in both eyes at or near bedtime (8PM to 10PM)
Phentolamine Ophthalmic Solution 0.75%	Phentolamine Ophthalmic Solution 0.75%	One drop in both eyes at or near bedtime (8PM to 10PM)

Primary Outcome Measures

Name	Time	Method
Percent of Subjects With 3 Lines mLCVA Improvement in Study Eye	8 days	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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Study Eye Mesopic Pupil Diameter (PD)	up to 15 days	Change from baseline in study eye mesopic PD
Percent of Subjects With mLCVA Improvement in Study Eye	up to 15 days	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)
Percent of Subjects With Photopic Low Contrast Visual Acuity (pLCVA) and mHCVA Improvement in Study Eye	up to 15 days	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
Percent Change From Baseline in Study Eye Mesopic Pupil Diameter (PD)	up to 15 days	Percent change from baseline in study eye mesopic PD

Trial Locations

Locations (17)

Clinical Site 13; 🇺🇸 Pittsburg, Kansas, United States

Clinical Site 1; 🇺🇸 Petaluma, California, United States

Clinical Site 19; 🇺🇸 Ogden, Utah, United States

Clinical Site 5; 🇺🇸 San Antonio, Texas, United States

Clinical Site 4; 🇺🇸 Elizabeth City, North Carolina, United States

Clinical Site 2; 🇺🇸 Fargo, North Dakota, United States

Clinical Site 6; 🇺🇸 Newport Beach, California, United States

Clinical Site 18; 🇺🇸 Jacksonville, Florida, United States

Clinical Site 3; 🇺🇸 Jacksonville, Florida, United States

Clinical Site 20; 🇺🇸 Edgewood, Kentucky, United States

Clinical Site 10; 🇺🇸 Palisades Park, New Jersey, United States

Clinical Site 9; 🇺🇸 High Point, North Carolina, United States

Clinical Site 14; 🇺🇸 Louisville, Kentucky, United States

Clinical Site 8; 🇺🇸 Pennington, New Jersey, United States

Clinical Site 22; 🇺🇸 High Point, North Carolina, United States

Clinical Test 15; 🇺🇸 Warwick, Rhode Island, United States

Clinical Site 11; 🇺🇸 Memphis, Tennessee, United States