Safety and Efficacy of T-2345 Compared to Xalatan in Subjects With Primary Open Angle Glaucoma or Ocular Hypertension

This is a Phase 3 study to evaluate the safety and efficacy of T-2345 dosed to one of both eyes once daily for 84 days compared to Xalatan dosed to one of both eyes once daily for 84 days in patients with elevated eye pressure.

The objective of this Phase 3 study is to evaluate the efficacy and safety of T-2345 nonpreserved ophthalmic solution (latanoprost 0.005%) in comparison to Xalatan® (latanoprost 0.005%) in subjects with primary open angle glaucoma (POAG) or ocular hypertension (OH).

This will be a randomized, multicenter, parallel-group, observer-masked study in approximately 380 evaluable subjects treated for 84 days. Subjects will have a history of POAG or OH and elevated intraocular pressure (IOP) and will have been adequately controlled (IOP ≤ 18 mm Hg) on latanoprost 0.005% ophthalmic solution monotherapy for at least 4 weeks.

Primary efficacy (IOP) will be assessed in the study eye at each visit by Goldmann applanation tonometry at all assessment visits.

Safety will be assessed at each visit by corrected Snellen Visual Acuity, slit lamp examination/anterior chamber cell count and flare and adverse event (AE) collection.

Primary Efficacy Endpoint is the between-group comparison of the mean IOP values at each time point at each of the Day 15, 42, and 84 visits.

Secondary Efficacy Endpoints include:

* Between-group comparison of the mean change from baseline in diurnal IOP measurements at all postbaseline visits.
* Between-group comparison of the mean change from baseline in IOP measurements at all times points at Day 15, Day 42 and Day 84.

Eligibility Criteria:
Inclusion Criteria:

1. Age 18 years or older.
2. POAG or OH with IOP treated and adequately controlled (IOP ≤ 18 mm Hg) with latanoprost 0.005% ophthalmic solution monotherapy for at least 4 weeks prior to Screening.
3. Each eye being treated with latanoprost 0.005% ophthalmic solution monotherapy must have mean IOP ≤ 18 mm Hg at Screening and mean IOP ≤ 28 mm Hg at Baseline; measurements will be taken at each visit at 8 AM, 10 AM, and 4 PM (each ± 30 minutes) with AM measurements of IOP at least 2 hours apart. If only one eye qualifies but both eyes have glaucoma and the fellow eye will require antiglaucoma medications, the subject does not qualify for the trial.
4. Stable visual field (VF), defined as no sign of VF degradation between two consecutive 30-2 or two consecutive 24-2 VF examinations. For subjects with no VF defect (eg, those with OH), a single, normal VF examination performed ˂ 6 months prior to the screening visit is allowed to determine eligibility. For patients who have an abnormal VF examination, the following criteria apply:

   * Two VF (most recent VF and past VF) examinations performed at least ≥ 6 months and ≤ 18 months apart must be compared;
   * The most recent VF examination should be performed \< 6 months prior to the Screening visit;
   * The past VF examination should be performed ≥ 6 months and ≤ 18 months prior to the most recent VF test.
5. Stable corrected Snellen visual acuity (VA) of better than 20/200 in the study eye. Patients must see ≥ 50% of the letters on a single line to accept that VA line.
6. Central corneal thickness 480-620 μm in the study eye.
7. Shaffer gonioscopic grade of ≥ 3 (in at least 3 quadrants) in both eyes.
8. Female subjects must be 1-year postmenopausal, surgically sterilized, or women of childbearing potential with a negative urine pregnancy test at Screening. Women of childbearing potential must use an acceptable form of contraception throughout the study. Acceptable methods include the use of at least one of the following: intrauterine (intrauterine device), hormonal (oral, injection, patch, implant, ring), barrier with spermicide (condom, diaphragm), or abstinence.
9. All subjects must provide signed written consent prior to participation in any study-related procedures.

Exclusion Criteria:

In the study eye:

1. A mean deviation of \< -20 dB on VF examination.
2. A mean IOP ˃ 28 mm Hg at Baseline.
3. Presence of a scotoma within 5° of fixation on VF examination.
4. Aphakia.
5. Use of any antiglaucoma medication in addition to latanoprost 0.005% ophthalmic solution within 2 weeks prior to Screening and any antiglaucoma medication (other than latanoprost) during the study period other than the randomized study medication.
6. Use of any topical ophthalmic steroid within 2 weeks prior to Baseline. A short course of oral steroids is acceptable if the course is completed \> 2 weeks prior to Screening. Inhaled and intranasal steroids are acceptable.
7. Use of topical nonsteroidal anti-inflammatory drug (NSAID) within 2 weeks prior to Baseline.
8. Use of any ophthalmic medications during the study period (nonpreserved artificial tears are allowed).
9. Ocular surgery or laser treatment of any kind in the study eye within 3 months prior to Baseline.
10. History of ocular allergy/inflammation and/or severe blepharitis and/or uveitis. Seasonal allergic conjunctivitis is acceptable (avoid enrollment of subjects who may experience seasonal flare-up during the study period). Mild blepharitis/blepharoconjunctivitis, typically associated with prostaglandin usage, on the lid is acceptable.
11. History of ocular trauma or ocular infection within 3 months of Screening.
12. History of herpes simplex keratitis.
13. Current proliferative diabetic retinopathy or age-related macular degeneration, unless deemed not clinically significant by the Investigator.
14. Severe dry eye (eg, clinically relevant superficial punctate keratitis, epithelial erosions of the cornea, and/or use of dry eye medication \[including artificial tears\] with a frequency exceeding 8 instillations per day).
15. Contact lens wear during the study period. Contact lens wear in an untreated fellow eye is allowed.
16. Any secondary glaucoma or OH (eg, congenital glaucoma, closed-angle glaucoma, uveitic glaucoma, or pseudoexfoliation syndrome).
17. Any severe glaucoma defined by cupping (cup-to-disc ratio ≥ 0.8).
18. Any non-laser glaucoma surgery.
19. Any abnormality preventing accurate assessment (eg, resulting in unreliable applanation tonometry or VF examination).

    General:
20. Pregnancy or lactation.
21. Uncontrolled asthma (defined as asthma that does not respond to the maximum guideline-directed therapy).
22. Allergy to benzalkonium chloride.
23. History of moderate or severe renal or hepatic impairment.
24. Participation in any study of an investigational product within 30 days prior to Screening or at any time during the study period.