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 1851,2
Completion Date March 15, 20211

1. https://clinicaltrials.gov/study/NCT04620213. 2. Pepose JS. et al. Ophthalmology. 2024. doi: https://doi.org/10.1016/ j.ophtha.2024.09.010.

Trial Design1,2

*Mydriatic agent randomization: 3:1:1.1,2 A: 2.5% phenylephrine;1,2 B: 1% tropicamide;1,2 C: Paremyd® †(1% hydroxyamphetamine/0.25% tropicamide).1–4 †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/NCT04620213; 2. MIRA-2 Ocuphire Pharma, Inc. Data on file; 3. RYZUMVITM (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
  • Healthy and well-controlled subjects1*
  • Ability to comply with all protocol-mandated procedures independently and to attend all scheduled office visits2
  • 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
*A well controlled subject is defined as a subject with no significant disease that might interfere with the study.
1. https://clinicaltrials.gov/study/NCT04620213; 2. MIRA-2 Ocuphire Pharma, Inc. Data on file.

Exclusion Criteria

Ophthalmic (in either eye)

  • Clinically significant ocular disease as deemed by the Investigator that might interfere with the study
  • Unwilling or unable to discontinue use of contact lenses at screening until study completion
  • Unwilling or unable to suspend use of topical medication at screening until study completion
  • Ocular trauma, ocular surgery or non-refractive laser treatment within the 6 months prior to screening
  • 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 (eg, OCuSOFT®lid scrub, SteriLid®, baby shampoo, etc.)
  • Recent or current evidence of ocular infection or inflammation
  • History of diabetic retinopathy or diabetic macular edema
  • Closed or very narrow angles that in the Investigator's opinion are potentially occludable if the subject’s pupil is dilated
  • History of any traumatic (surgical or nonsurgical) or non-traumatic condition affecting the pupil or iris
  • Known allergy or contraindication to any component of the mydriatic agents or the vehicle formulation
  • History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal
https://clinicaltrials.gov/study/NCT04620213.

Exclusion Criteria

Systemic:

  • Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists
  • Clinically significant systemic disease that might interfere with the study
  • 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
  • Participation in any investigational study within 30 days prior to screening
  • Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
  • Resting HR outside the range of ≤50 to ≥110 bpm
  • Hypertension with resting DBP >105 mmHg or SBP >160 mmHg
bpm, beats per minute; DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.
https://clinicaltrials.gov/study/NCT04620213.

Primary Endpoint

  • Percentage of subjects’ study eyes returning to ≤0.2 mm from baseline pupil diameter (PD) at 90 minutes
https://clinicaltrials.gov/study/NCT04620213.

Secondary Endpoints

  • Percentage of subjects with study eyes returning to ≤0.2 mm from baseline pupil diameter (PD) at each remaining time point (30 min, 60 min, 2 hours, 3 hours, 4 hours, 6 hours, 24 hours)1
  • Change (mm) from maximum pharmacologically-induced mydriatic PD from 0 minutes to 24 hours1
  • Percentage of subjects with unchanged accommodation from baseline up to 6 hours1
  • Time (hours) to return to ≤0.2 mm from baseline PD2
1. https://clinicaltrials.gov/study/NCT04620213; 2. MIRA-2 Ocuphire Pharma, Inc. Data on file.

Safety Endpoint(s)

  • Primary safety measures were conjunctival hyperemia,*subjective ocular tolerability, and AEs
  • Other safety measures were impairment in visual acuity (BCDVA and DCNVA), IOP, subject questionnaire, and systemic safety, as measured by HR and BP
*Assessed visually with the CCLRU bulbar redness scale.
AE, adverse event; 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-2 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, and Native Hawaiian or other Pacific Islander.1
D, diopter; PD, pupil diameter; POS, phentolamine ophthalmic solution; SD, standard deviation.
1. https://clinicaltrials.gov/study/NCT04620213; 2. MIRA-2 Ocuphire Pharma, Inc. Data on file.

Baseline Characteristics (2/2)

*Data presented as mean (SD), unless otherwise specified;1,2 †Paremyd is a registered trademark of Akorn, Inc. ‡For BCDVA, the number of letters read is from the 4-meter distance only, so that 55 letters read is equivalent to a Snellen acuity of 20/20.2
BCDVA, best-corrected distance visual acuity; DCNVA, distance-corrected near visual acuity; IOP, intraocular pressure; POS, phentolamine ophthalmic solution; SD, standard deviation.
1. https://clinicaltrials.gov/study/NCT04620213; 2. MIRA-2 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Primary and Secondary Endpoints

The mITT population included all randomized subjects who received 1 or 2 drops of study medication 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-2 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Primary and Secondary Endpoints

*p<0.01;1 The mITT population included all randomized subjects who received 1 or 2 drops of study medication and then had at least one scheduled PD measurement during visit 1. The mITT population was used for the primary endpoint analysis (90 minutes) 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-2 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

*p<0.01;1 The mITT population included all randomized subjects who received 1 or 2 drops of study medication 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-2 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

*Paremyd is a registered trademark of Akorn, Inc. †p<0.01;1 The mITT population included all randomized subjects who received 1 or 2 drops of study medication 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-2 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

The PP population included all subjects in the mITT population who had 2 drops of study medication in their study eye, had all scheduled PD measurements during visit 1, had an increase of >0.2 mm in PD in the study eye at time 0 min compared to baseline (-1 hr), and had no major protocol deviations. The PP population was used to analyze selected secondary efficacy endpoints, with subjects included in their randomized treatment regardless of the treatment they actually received.1
mITT, modified Intention-to-Treat; PP, per-protocol; PD, pupil diameter; POS, phentolamine ophthalmic solution.
1. MIRA-2 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

*Paremyd is a registered trademark of Akorn, Inc. †p<0.05; The PP population included all subjects in the mITT population who had 2 drops of study medication in their study eye, had all scheduled PD measurements during visit 1, had an increase of >0.2 mm in PD in the study eye at time 0 min compared to baseline (-1 hr), and had no major protocol deviations. The PP population was used to analyze selected secondary efficacy endpoints, with subjects included in their randomized treatment regardless of the treatment they actually received.1
mITT, modified Intention-to-Treat; PP, per-protocol; PD, pupil diameter; POS, phentolamine ophthalmic solution.
1. MIRA-2 Ocuphire Pharma, Inc. Data on file.

Efficacy Outcome Measures – Secondary Endpoints

The PP population included all subjects in the mITT population who had 2 drops of study medication in their study eye, had all scheduled PD measurements during visit 1, had an increase of >0.2 mm in PD in the study eye at time 0 min compared to baseline (-1 hr), and had no major protocol deviations. The PP population was used to analyze selected secondary efficacy endpoints, with subjects included in their randomized treatment regardless of the treatment they actually received.1
mITT, modified Intention-to-Treat; PP, per-protocol; PD, pupil diameter; POS, phentolamine ophthalmic solution; SD, standard deviation.
1. MIRA-2 Ocuphire Pharma, Inc. Data on file.

Safety Outcome Measures

*Data presented as n (%);1,2 †In counting the number of AEs reported, an AE is defined as an event with a unique subject identification number, system organ class, preferred term, and site. Bilateral ocular events are counted twice (i.e., once for each eye). A subject reporting >1 TEAE (preferred term) is only counted once within the system organ class and once within the preferred term.1
AE, adverse event; IOP, intraocular pressure; POS, phentolamine ophthalmic solution​; SAE, serious adverse event; TEAE, treatment-emergent adverse event.
1. MIRA-2 Ocuphire Pharma, Inc. Data on file; 2. https://clinicaltrials.gov/study/NCT04620213.