Clinical trial NCT05134974: Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis (MIRA-3)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mydriasis
Dilation
Keywords: Nyxol
Pharmacologically Induced Mydriasis
Dilation
Lead sponsor: Ocuphire Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2021-11-26
Enrollment: 368
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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
* To evaluate the systemic exposure of Nyxol on pharmacokinetic (PK) sampling

Detailed description: A randomized, parallel arm, double-masked, placebo-controlled Phase 3 study in at least 330 randomized subjects, 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 2:1, Nyxol or placebo (vehicle). Stratification by iris color will be 1:1, light or dark rides. The mydriatic agent randomization will be 3:1:1 (2.5% phenylephrine, 1% tropicamide, and Paremyd).

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.

Blood sampling for Nyxol PK measurements will be conducted in a subset of approximately 30 adult subjects at approximately two select study sites.

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

Eligibility criteria: Inclusion Criteria:

1. Males or females ≥ 12 years of age
2. Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits

Exclusion Criteria:

1. Clinically significant ocular disease as deemed by the Investigator (eg, glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca) 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, with the exception of lid scrubs with OTC products (eg, OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.)
6. Recent or current evidence of ocular infection or inflammation in either eye (such as current evidence of clinically significant blepharitis, conjunctivitis, or keratitis). Subjects must be symptom-free for at least 7 days prior to screening
7. Closed or very narrow-angle that in the Investigator's opinion is potentially occludable if the subject's pupil is dilated
8. Prior participation in a study involving the use of Nyxol for the reversal of mydriasis
9. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists
10. Clinically significant systemic disease (eg, uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that might interfere with the study
11. Participation in any investigational study within 30 days prior to screening
12. Resting heart rate (HR) outside the normal range (50-110 beats per minute) at the Screening Visit.
13. Hypertension with resting diastolic blood pressure (BP)\>105 mmHg or systolic BP \> 160 mmHg at the Screening Visit.

Primary outcomes:
measure: Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline
timeFrame: 90 minutes
Secondary outcomes:
measure: Percent of Subjects' Study Eyes With Pupil Diameter Returning to Baseline
timeFrame: 30 minutes to 24 hours
measure: Pupil Diameter (Change From Max)
timeFrame: 30 minutes to 24 hours
measure: Percent of Subjects With Unchanged Accommodation From Baseline
timeFrame: 90 minutes to 6 Hours
measure: Change From Baseline in Best-Corrected Distance Visual Acuity (BCDVA) Under Normal Photopic Lighting Without Glare Conditions
timeFrame: 6 hours
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Clinical Site 10
state: California
city: Westminster
country: United States
facility: Clinical Site 12
state: California
city: Delray Beach
country: United States
facility: Clinical Site 9
state: Florida
city: Longwood
country: United States
facility: Clinical Site 8
state: Florida
city: Morrow
country: United States
facility: Clinical Site 6
state: Georgia
city: Roswell
country: United States
facility: Clinical Site 1
state: Georgia
city: Lake Villa
country: United States
facility: Clinical Site 13
state: Illinois
city: Pittsburg
country: United States
facility: Clinical Site 5
state: Kansas
city: Bloomington
country: United States
facility: Clinical Site 2
state: Minnesota
city: Garner
country: United States
facility: Clinical Site 15
state: North Carolina
city: Athens
country: United States
facility: Clinical Site 4
state: Ohio
city: Shrewsbury
country: United States
facility: Clinical Site 14
state: Pennsylvania
city: Warwick
country: United States
facility: Clinical Site 7
state: Rhode Island
city: Sioux Falls
country: United States
facility: Clinical Site 11
state: South Dakota
city: Memphis
country: United States
facility: Clinical Site 3
state: Tennessee
Study officials:
References: