Safety and Efficacy of Ophthalmic Phentolamine Mesylate in Glaucoma

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

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.

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.

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