Safety and Efficacy of Ophthalmic Phentolamine Mesylate in Glaucoma

• ClinicalTrials.gov Identifier: NCT03960866
• Recruitment Status: Completed
• First Posted: May 23, 2019
• Last Update Posted: October 14, 2019
• Sponsor: Ocuphire Pharma, Inc.
• Information provided by (Responsible Party): Ocuphire Pharma, Inc.

Tracking Information

• First Submitted Date: May 21, 2019
• First Posted Date: May 23, 2019
• Last Update Posted Date: October 14, 2019
• Actual Study Start Date: May 28, 2019
• Actual Primary Completion Date: September 11, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2019)

Intraocular Pressure [ Time Frame: 14 days ]

change from Baseline in mean diurnal IOP in the study eye

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 22, 2019)

• Distance Visual Acuity [ Time Frame: 14 days ]
  Change in Distance Visual Acuity from Baseline measured at 4 meters (photopic and mesopic)
• Near Visual Acuity [ Time Frame: 14 days ]
  Change in Near Visual Acuity from Baseline measured at 16 inches (photopic and mesopic)
• Pupil Diameter [ Time Frame: 14 days ]
  Change and percent change from Baseline in Pupil Diameter (mesopic and photopic)
• Conjunctival Hyperemia [ Time Frame: 14 days ]
  Change in Conjunctival Hyperemia score

Original Secondary Outcome Measures (submitted: May 21, 2019)

• Distance Visual Acuity [ Time Frame: 14 days ]
  Change in Distance Visual Acuity from Baseline measured at 4 meters (photopic and mesopic)
• Near Visual Acuity [ Time Frame: 14 days ]
  Change in Near Visual Acuity from Baseline measured at 16 inches (photopic and mesopic)
• Pupil Diameter [ Time Frame: 14 days ]
  Change and percent change from Baseline in Pupil Diameter (mesopic and photopic)
• Adverse Events [ Time Frame: 14 days ]
  Safety and Tolerability

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Ophthalmic Phentolamine Mesylate in Glaucoma
• Official Title: Randomized, Placebo-Controlled, Double-Masked Study of the Safety and Efficacy of Phentolamine Mesylate Ophthalmic Solution in Subjects With Open Angle Glaucoma or Ocular Hypertension

Brief Summary

The objectives of this study are:

• To evaluate the efficacy of Phentolamine Mesylate to lower intra-ocular pressure (IOP) in the treatment of Open-Angle Glaucoma (OAG) and Ocular Hypertension (OHT).
• To evaluate the ocular and systemic safety of Phentolamine Mesylate compared to its vehicle.
• To evaluate additional efficacy of Phentolamine Mesylate to improve visual performance.

• Detailed Description: Placebo-controlled double-masked, multiple dose Phase 2 study in 40 patients with IOP ≥ 22 and ≤30 mmHg, evaluating ocular and systemic safety and efficacy following administration of Phentolamine mesylate 1.0% QD at 8PM to 10PM in both eyes for 14 days.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Open Angle Glaucoma
• Ocular Hypertension

Intervention

• Drug: Phentolamine Mesylate Ophthalmic Solution 1%
  Topical Sterile Ophthalmic Solution
  Other Name: Nyxol®
• Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo)
  Topical Sterile Ophthalmic Solution

Study Arms

• Experimental: Nyxol Ophthalmic Solution 1%
  1 drop in each eye daily (QD) at or before bedtime (8pm to 10pm) for 14 days
  Intervention: Drug: Phentolamine Mesylate Ophthalmic Solution 1%
• Placebo Comparator: Nyxol Ophthalmic Solution Vehicle
  1 drop in each eye daily (QD) at or before bedtime (8pm to 10pm) for 14 days
  Intervention: Other: Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 10, 2019): 39
• Original Estimated Enrollment (submitted: May 21, 2019): 40
• Actual Study Completion Date: September 11, 2019
• Actual Primary Completion Date: September 11, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 18 years of age or greater
2. Diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT). A reported history of untreated OHT with IOP ≥22mmHg and ≤ 30mmHg is preferred.
3. Untreated or treated OAG/OHT with 2 or fewer ocular hypotensive medications.
4. Untreated (post-washout) mean IOP ≥ 22mmHg and ≤30mmHg in the study eye at the Qualification Visit (8AM).
5. Corrected visual acuity in each eye +1.0 logMAR or better by Early Treatment Diabetic Retinopathy Study (ETDRS) in each eye (equivalent to 20/200 or better) at the Screening Visit and Qualification Visit.
6. Otherwise healthy and well-controlled subjects.
7. Able and willing to give signed informed consent and follow study instructions.
8. Able to self-administer study medication or to have study medication administered by a caregiver throughout the study period.

Exclusion Criteria:

1. Closed or very narrow angles (Grade 0-1, Shaffer)
2. Glaucoma: pseudo-exfoliation or pigment dispersion component
3. Known hypersensitivity to any α-adrenoceptor antagonists
4. Previous laser and/or non-laser glaucoma surgery or procedure in either eye
5. Refractive surgery in either eye
6. Ocular trauma in either eye within the 6 months prior to Screening, or ocular surgery or non-refractive laser treatment within the 3 months prior to Screening
7. Recent or current evidence of ocular infection or inflammation in either eye
8. Ocular medication in either eye of any kind within 30 days of Screening
9. Clinically significant ocular disease in either eye
10. History of diabetic retinopathy
11. Contact lens wear within 3 days prior to and for the duration of the study
12. Central corneal thickness in either eye >600 μm at Screening
13. Any abnormality in either eye preventing reliable applanation tonometry
14. Known hypersensitivity or contraindication to α- and/or β-adrenoceptor antagonists
15. Clinically significant systemic disease that might interfere with the study
16. Participation in any investigational study within 30 days prior to Screening
17. Use of any topical or systemic adrenergic or cholinergic drugs up to 30 days prior to Screening, or during the study
18. Changes in systemic medication that could have an effect on IOP within 30 days prior to Screening
19. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
20. Resting heart rate outside the normal range (50-110 beats per minute) at Screening or Qualification Visit
21. Hypertension with resting diastolic blood pressure (BP) > 105 mmHg or systolic BP > 160 mmHg at the Screening or Qualification Visit

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03960866
• Other Study ID Numbers: OPI-NYXG-201 (ORION-1)
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Ocuphire Pharma, Inc.
• Study Sponsor: Ocuphire Pharma, Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ocuphire Pharma, Inc.
• Verification Date: October 2019