Safety and Efficacy of 0.75% Phentolamine Ophthalmic Solution With Pilocarpine Eye Drops in Subjects With Presbyopia

Molecule Phentolamine ophthalmic solution 0.75%
Therapeutic focus Presbyopia
Phase 2
Status Completed
Participants 150
Completion Date June 30, 2021

The use of MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established.
https://clinicaltrials.gov/study/NCT04675151.

Trial Design1,2

The use of MR-141 for Presbyopia is currently under investigation and its safety and efficacy have not been established.
LDP, low-dose pilocarpine; POS, phentolamine ophthalmic solution 0.75%.
1. https://clinicaltrials.gov/study/NCT04675151; 2. Pepose J.S., et al. ASCRS 2021 Presentation (Paper #76645).
Available at: https://d1io3yog0oux5.cloudfront.net/_024aeac324ab6f96d110f6a3fb5dd959/ocuphire/db/357/3653/pdf/ASCRS+2021+VEGA-1+Presentation_FINAL.pdf

Inclusion Criteria

  • ≥40 and ≤64 years of age
  • BCDVA of 0.0 LogMAR (20/20 Snellen equivalent) or better in each eye under photopic conditions
  • DCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse under photopic conditions in each eye and binocularly
  • Subjects who depend on reading glasses or bifocals in which their binocular best-corrected near VA is 0.1 LogMAR (20/25 Snellen equivalent) or better
The use of  MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established. 
BCDVA, best-corrected distance visual acuity; DCNVA, distance-corrected near visual acuity; LogMAR, logarithm of the minimum angle of resolution; VA, visual acuity.
https://clinicaltrials.gov/study/NCT04675151.

Exclusion Criteria

Ophthalmic:*

  • Use of any topical prescription or over-the-counter (OTC) ophthalmic medications within 7 days of screening until study completion
  • Use of any OTC artificial tears (preserved or unpreserved) at least once per day within 7 days of screening until study completion
  • Current use of any topical ophthalmic therapy for dry eye
  • Tear break-up time of <5 seconds or corneal fluorescein staining (CFS) Grade ≥2 in the inferior zone or ≥1 in the central zone using the National Eye Institute scale
  • Clinically significant ocular disease that might interfere with the study as deemed by the Investigator
  • Recent or current evidence of ocular infection or inflammation
  • Any history of herpes simplex or herpes zoster keratitis
  • History of diabetic retinopathy or diabetic macular edema
  • Known allergy, hypersensitivity, or contraindication to any component of the phentolamine, pilocarpine, or vehicle (placebo) formulations
  • History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal
  • Ocular trauma, ocular surgery, ocular laser treatment within 6 months prior to screening
  • Use of multifocal intraocular lenses
  • History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris
  • Unwilling or unable to discontinue contact lens use
  • Conjunctival hyperemia ≥Grade 2 on the Cornea and Contact Lens Research Unit (CCLRU) 4-point scale
The use of  MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established. 
*In either eye.
https://clinicaltrials.gov/study/NCT04675151.

Exclusion Criteria

Systemic:

  • Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists or any systemic cholinergic parasympathomimetic agents
  • Clinically significant systemic disease that might interfere with the study as deemed by the Investigator
  • 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
The use of  MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established. 
bpm, beats per minute; DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.
https://clinicaltrials.gov/study/NCT04675151.

Primary Endpoint

  • Percentage of subjects with ≥15 letters of improvement in photopic binocular DCNVA from baseline to visit 2 at 1 hour with POS + LDP compared to placebo alone
The use of  MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established. 
DCNVA, distance-corrected near visual acuity; LDP, low-dose pilocarpine; POS, phentolamine ophthalmic solution.
https://clinicaltrials.gov/study/NCT04675151.

Key Secondary Endpoints

  • Percentage of subjects with improvement of ≥15 letters in DCNVA (photopic) at 1 hour and with <5 letters of loss in photopic binocular BCDVA from baseline to visit 2 at 30 min, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours comparing POS + LDP to POS alone, placebo + LDP, and placebo alone
  • Percentage of subjects with improvement of ≥5, ≥10, and ≥15 letters in DCNVA (photopic) from baseline to visit 2 at 30 min, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours comparing POS + LDP to POS alone, placebo + LDP, and placebo alone
  • Change in DCNVA (photopic) from baseline to visit 2 at 30 min, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours comparing POS + LDP to POS alone, placebo + LDP, and placebo alone
  • Percentage of subjects with improvement in DCNVA (mesopic) from baseline to visit 2 at 2 hours, 4 hours, and 6 hours of ≥5, ≥10, and ≥15 letters comparing POS + LDP to POS alone, placebo + LDP, and placebo alone
The use of  MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established. 
BCDVA, best-corrected distance visual acuity; DCNVA, distance-corrected near visual acuity; LDP, low-dose pilocarpine; POS, phentolamine ophthalmic solution.
VEGA-1 Ocuphire Pharma, Inc. Data on file.

Safety Endpoints

  • Subjective ocular tolerability1
  • Conjunctival hyperemia1
  • Intraocular pressure (IOP)1
  • Biomicroscopy1
  • Ophthalmoscopy1
  • Systemic safety, as measured by HR and BP2
  • Adverse events (AEs)1 and serious adverse events (SAEs)2
The use of  MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established. 
BP, blood pressure; HR, heart rate.
1. VEGA-1 Ocuphire Pharma, Inc. Data on file; 2. https://clinicaltrials.gov/study/NCT04675151.

Baseline Characteristics

The use of  MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established. 
*Data presented as mean (SD), unless otherwise specified; †Photopic; ‡Binocular; §Study eye.
BCDVA, best-corrected distance visual acuity; DCIVA, distance-corrected intermediate visual acuity; DCNVA, distance-corrected near visual acuity; IOP, intraocular pressure; LDP, low-dose pilocarpine; PD, pupil diameter; POS, phentolamine ophthalmic solution; SD, standard deviation.
VEGA-1 Ocuphire Pharma, Inc. Data on file.

Percent of Subjects With Improvement ≥ 15 Letters From Baseline in Photopic Binocular DCNVA by Time Point 1,2

The use of MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established.
DCNVA, distance-corrected near visual acuity; POS, phentolamine ophthalmic solution 0.75%; LDP, low dose pilocarpine
1. https://clinicaltrials.gov/study/NCT04675151. 2. Pepose J.S., et al. ASCRS 2021 Presentation (Paper #76645).
Available at: https://d1io3yog0oux5.cloudfront.net/_024aeac324ab6f96d110f6a3fb5dd959/ocuphire/db/357/3653/pdf/ASCRS+2021+VEGA-1+Presentation_FINAL.pdf.
 

Percent of Subjects With Improvement ≥ 15 Letters From Baseline in Photopic Binocular DCNVA And < 5 Letter Loss in Photopic BCDVA by Time Point 1,2

The use of  MR-141 for Presbyopia is currently under investigation and its safety and efficacy have not been established.
BCDVA, best-corrected distance visual acuity; DCNVA, distance-corrected near visual acuity; LDP, low-dose pilocarpine; POS, phentolamine ophthalmic solution 0.75%.
https://clinicaltrials.gov/study/NCT04675151. 2. Pepose J.S., et al. ASCRS 2021 Presentation (Paper #76645).
Available at: https://d1io3yog0oux5.cloudfront.net/_024aeac324ab6f96d110f6a3fb5dd959/ocuphire/db/357/3653/pdf/ASCRS+2021+VEGA-1+Presentation_FINAL.pdf.

Mean Photopic Pupil Diameter in Best Eye by Time Point1,2

The use of  MR-141 for Presbyopia is currently under investigation and its safety and efficacy have not been established.
BCDVA, best-corrected distance visual acuity; DCNVA, distance-corrected near visual acuity; LDP, low-dose pilocarpine; POS, phentolamine ophthalmic solution 0.75%.
https://clinicaltrials.gov/study/NCT04675151. 2. Pepose J.S., et al. ASCRS 2021 Presentation (Paper #76645).
Available at: https://d1io3yog0oux5.cloudfront.net/_024aeac324ab6f96d110f6a3fb5dd959/ocuphire/db/357/3653/pdf/ASCRS+2021+VEGA-1+Presentation_FINAL.pdf.

Safety Outcome Measures*

The use of  MR-141 for Presbyopia is currently being investigated and its safety and efficacy have not been established. 
*Data presented as n (%); †Collected by systematic assessment.
AE, adverse event; LDP, low-dose pilocarpine; POS, phentolamine ophthalmic solution; SAE, serious adverse event.
https://clinicaltrials.gov/study/NCT04675151.