Randomized, Parallel Arm, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of 0.75% Phentolamine Ophthalmic Solution to Reverse Pharmacologically-Induced Mydriasis in Healthy Subjects1

Molecule Phentolamine ophthalmic solution 0.75%1,2
Therapeutic focus Reversal of pharmacologically-induced mydriasis1,2
Phase 31,2
Status Completed1,2
Participants 3681,2
Completion Date March 29, 20221

1. https://clinicaltrials.gov/study/NCT05134974. 2. Pepose JS. et al. Ophthalmology. 2024. doi: https://doi.org/10.1016/ j.ophtha.2024.09.010.

Trial Design1,2

*Mydriatic agent randomization: 3:1:1. A: 2.5% phenylephrine;2 B: 1% tropicamide;2 C: Paremyd® †(1% hydroxyamphetamine/0.25% tropicamide).3,4 
†Paremyd is a registered trademark of Akorn, Inc.
h, hour; max, maximum; min, minute; PD, pupil diameter; POS, phentolamine ophthalmic solution; US, United States.
1. https://clinicaltrials.gov/study/NCT05134974; 2. MIRA-3 Ocuphire Pharma, Inc. Data on file; 3. RYZUMVI™(phentolamine ophthalmic solution). Prescribing Information. Available at: https://www.ryzumvi.com/files/prescribing-information.pdf; 4. PAREMYD® (hydroxyamphetamine hydrobromide/ tropicamide ophthalmic solution). Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/19261s8lbl.pdf.

Inclusion Criteria

  • ≥12 years of age1,2
  • Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits1,2
  • Adults (≥18 years of age) willing to give written informed consent to participate in this study. Children aged 12 to 17 years to provide signed assent form, as well as a separate parental/Legal Guardian consent2
1. https://clinicaltrials.gov/study/NCT05134974; 2. MIRA-3 Ocuphire Pharma, Inc. Data on file.

Exclusion Criteria

Ophthalmic:*1

  • Clinically significant ocular disease as deemed by the Investigator (e.g., glaucoma, corneal edema, uveitis, severe keratoconjunctivitis sicca) that might interfere with the study2
  • Unwilling or unable to discontinue use of contact lenses at screening until study completion2
  • Unwilling or unable to suspend use of topical medication at screening until study completion2
  • Ocular trauma, ocular surgery, or non-refractive laser treatment within the 6 months prior to screening2
  • Use of any topical prescription or over-the-counter (OTC) ophthalmic medications within 7 days of screening, with the exception of lid scrubs with OTC products (e.g., OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.)2
  • Recent (within 7 days) or current evidence of ocular infection or inflammation (such as current evidence of clinically significant blepharitis, conjunctivitis, or keratitis)2
  • Closed or very narrow-angle that in the Investigator's opinion is potentially occludable if the subject’s pupil is dilated2
  • Prior participation in a study involving the use of 0.75% phentolamine ophthalmic solution (POS) for the reversal of mydriasis2
  • History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris1
  • History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal1
*In either eye.2
1. MIRA-3 Ocuphire Pharma, Inc. Data on file; 2. https://clinicaltrials.gov/study/NCT05134974.

Exclusion Criteria

Systemic1:

  • Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists2
  • Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that might interfere with the study2
  • Participation in any investigational study within 30 days prior to screening2
  • Resting HR outside the range of ≤50 to ≥110 bpm at the screening visit2
  • Hypertension with resting DBP >105 mmHg or SBP >160 mmHg at the screening visit2
  • 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 study1
  • Females of childbearing potential who were pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control1
bpm, beats per minute; DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.
1. MIRA-3 Ocuphire Pharma, Inc. Data on file; 2. https://clinicaltrials.gov/study/NCT05134974.

Primary Endpoint

  • Percentage of subjects with study eye pupil diameter (PD) returning to baseline (defined as ≤0.2 mm above baseline PD) at 90 minutes
https://clinicaltrials.gov/study/NCT05134974.

Key Secondary Endpoints1,2

  • Percentage of subjects returning to ≤0.2 mm from baseline PD at 0 min, 30 min, 60 min, 90 min [fellow eye], 2 hours, 3 hours, 4 hours, 6 hours, 24 hours
  • Change (mm) from maximum pharmacologically-induced mydriatic PD (0 min) at 30 min, 60 min, 90 min, 2 hours, 3 hours, 4 hours, 6 hours, 24 hours
  • Percentage of subjects with unchanged accommodation from baseline (-1 hour) at 0 min, 90 min, 2 hours, 3 hours, 6 hours
  • Change (letters) in BCDVA under normal photopic lighting without glare conditions from baseline (-1 hour) at 0 min, 60 min, 2 hours, 6 hours
BCDVA, best-corrected distance visual acuity; PD, pupil diameter.
1. https://clinicaltrials.gov/study/NCT05134974; 2. MIRA-3 Ocuphire Pharma, Inc. Data on file.

Safety Endpoints

  • Primary safety measures were conjunctival hyperemia, * impairment in visual acuity (BCDVA and DCNVA), subjective ocular tolerability, and adverse events (AEs)
  • Other safety measures were IOP, subject questionnaire, and systemic safety, as measured by HR and BP†
*Assessed visually with the CCLRU bulbar redness scale;†Urine pregnancy tests for females of childbearing potential were conducted at screening prior to dosing of study medication.
BCDVA, best-corrected distance visual acuity; BP, blood pressure; CCLRU, Cornea and Contact Lens Research Unit;
DCNVA, distance-corrected near visual acuity; HR, heart rate; IOP, intraocular pressure.
MIRA-3 Ocuphire Pharma, Inc. Data on file.

Baseline Characteristics (1/2)

*Data presented as mean (SD), unless otherwise specified;1,2 †Includes American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, and unknown or not reported.1
D, diopter; PD, pupil diameter; POS, phentolamine ophthalmic solution; SD, standard deviation.
1. https://clinicaltrials.gov/study/NCT05134974; 2. MIRA-3 Ocuphire Pharma, Inc. Data on file.

Baseline Characteristics (2/2)

*Data presented as mean (SD), unless otherwise specified;† The number of letters read is from the 4-meter distance only, so that 55 letters read is equivalent to a Snellen acuity of 20/20.
BCDVA, best-corrected distance visual acuity; DCNVA, distance-corrected near visual acuity; IOP, intraocular pressure; POS, phentolamine ophthalmic solution; SD, standard deviation.
MIRA-3 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Primary and Secondary Endpoints

The mITT population included all randomized subjects who received 2 drops of study medication in the study eye and then had at least one scheduled PD measurement during visit 1. The mITT population was used for the primary endpoint analysis and to analyze selected secondary efficacy endpoints, with subjects included in their randomized treatment regardless of the treatment they actually received.2 
mITT, modified Intention-to-Treat; PD, pupil diameter; POS, phentolamine ophthalmic solution.
1. RYZUMVI™ (phentolamine ophthalmic solution). Prescribing Information. Available at: https://www.ryzumvi.com/files/prescribing-information.pdf; 2. MIRA-3 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

*p<0.01;1 The mITT population included all randomized subjects who received 2 drops of study medication in the study eye and then had at least one scheduled PD measurement during visit 1. The mITT population was used for the primary endpoint analysis and to analyze selected secondary efficacy endpoints, with subjects included in their randomized treatment regardless of the treatment they actually received.2
mITT, modified Intention-to-Treat; PD, pupil diameter; POS, phentolamine ophthalmic solution.
1. RYZUMVI™ (phentolamine ophthalmic solution). Prescribing Information. Available at: https://www.ryzumvi.com/files/prescribing-information.pdf; 2. MIRA-3 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

*p<0.01;1 The mITT population included all randomized subjects who received 2 drops of study medication in the study eye and then had at least one scheduled PD measurement during visit 1. The mITT population was used for the primary endpoint analysis and to analyze selected secondary efficacy endpoints, with subjects included in their randomized treatment regardless of the treatment they actually received.2
mITT, modified Intention-to-Treat; PD, pupil diameter; POS, phentolamine ophthalmic solution.
1. RYZUMVI™ (phentolamine ophthalmic solution). Prescribing Information. Available at: https://www.ryzumvi.com/files/prescribing-information.pdf; 2. MIRA-3 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

*Paremyd is a registered trademark of Akorn, Inc. †p<0.01;1 l The mITT population included all randomized subjects who received 2 drops of study medication in the study eye and then had at least one scheduled PD measurement during visit 1. The mITT population was used for the primary endpoint analysis and to analyze selected secondary efficacy endpoints, with subjects included in their randomized treatment regardless of the treatment they actually received.2
mITT, modified Intention-to-Treat; PD, pupil diameter; POS, phentolamine ophthalmic solution.
1. RYZUMVI™ (phentolamine ophthalmic solution). Prescribing Information. Available at: https://www.ryzumvi.com/files/prescribing-information.pdf; 2. MIRA-3 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

The safety population included all randomized subjects who received at least 1 drop of study medication.
BCDVA, best-corrected distance visual acuity; POS, phentolamine ophthalmic solution.
MIRA-3 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

*Data presented as n (%); †Collected by systematic assessment.
POS, phentolamine ophthalmic solution.
https://clinicaltrials.gov/study/NCT05134974.