A Prospective Study to Assess the Hypotensive Efficacy of Rho-Kinase Inhibitor AR-12286 Ophthalmic Solution 0.5% and 0.7% in Patients With Exfoliation Syndrome and Ocular Hypertension or Glaucoma
Condition: Exfoliation Syndrome; Ocular Hypertension; Open Angle Glaucoma
MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Exfoliation Syndrome; Hypertension; Syndrome
Intervention: AR-12286
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 10.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      Glaucoma is the world's the second leading cause of irreversible blindness. The World Health
      Organization (WHO) estimated the incidence of blindness due to glaucoma to be 4.4 million
      people worldwide in 2002. Intraocular pressure (IOP) is the sole proven modifiable risk
      factor for the development and progression of glaucomatous optic neuropathy. Medical therapy
      is aimed at lowering IOP in order to prevent or slow progression.

      Exfoliation syndrome (XFS) is the most common identifiable cause of open-angle glaucoma,
      affecting an estimated 60 to 70 million people worldwide. Approximately two-thirds of
      patients have disease in only one eye on clinical examination; however, XFS is detectable in
      the other eye with conjunctival biopsy. XFS is also a systemic disease, with effects on the
      cardiovascular and cerebrovascular systems.

      Patients with XFS are twice as likely to convert from ocular hypertension to glaucoma.
      Glaucoma in XFS is more severe than primary open angle glaucoma. There is greater diurnal IOP
      fluctuation, greater visual field loss and optic nerve head damage at the time of diagnosis,
      poorer response to medications, more rapid visual field progression and more frequent need
      for surgery.

      Because you meet eligibility criteria for our study, we ask for your consent to participate
      in the study described below. In brief, you will be taking an investigational drug (AR-12286,
      rho-kinase Inhibitor) at either 0.5% or 0.7% once a day for 6 months. This drug is currently
      being tested in patients with primary open-angle glaucoma, but not yet in glaucoma in
      exfoliation syndrome. Because of the mechanism of glaucoma in XFS and the mechanism of action
      of rho-kinase inhibitors, there is reason to think it would be more effective in eyes with
      XFS and glaucoma than in primary open-angle glaucoma (ordinary glaucoma). There will be a
      baseline and study day 1 visit, week 1 visit, month 1 and 3 visit, week 13 visit, month 6
      visit and a week 25 visit; for a total of 7 office visits.
    

Eligibility criteria:

        Inclusion Criteria:

          -  50-85 y.o.

          -  Male and Female

          -  Exfoliation Syndrome and ocular hypertension or mild or moderate exfoliative glaucoma

          -  IOP ≥22 mmHg prior to initiation of treatment in one or both eyes with two
             measurements taken two hours apart

          -  No previous intraocular surgery except clear cornea phacoemulsification

          -  Corrected visual acuity in both eyes ≥20/50 in the eligible eye

          -  Not more than 6 diopters spherical equivalent on the study eye

          -  Not more than 3 diopters cylinder equivalent on the study eye

          -  Have given written informed consent, prior to any investigational procedures

          -  Ability to attend for the 6-month duration of the study

        Exclusion Criteria:

          -  Open angle glaucoma other than exfoliative glaucoma

          -  Closed angle glaucoma (primary or secondary)

          -  Intraocular pressure >30 mm Hg

          -  Severe exfoliation glaucoma

          -  Known hypersensitivity to any component of the formulation (benzalkonium chloride,
             etc.), or to topical anesthetics

          -  Previous intraocular surgery except clear cornea phacoemulsification

          -  Clinically significant ocular disease (e.g. corneal edema, uveitis, severe
             keratoconjunctivitis sicca) which might interfere with the study

          -  Ocular medication of any kind within 30 days of base-line visit, with the exception of
             ocular hypotensive medications and/or lubricating drops for dry eye (which may be used
             throughout the study)

          -  Any abnormality preventing reliable applanation tonometry of either eye

          -  Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia
             gravis, hepatic, renal, endocrine or cardiovascular disorders) which might interfere
             with the study

          -  Changes of systemic medication that could have a substantial effect on IOP anticipated
             during the study

          -  Participation in any investigational study within the past 30 days

          -  Inability to perform reliable VF testing

          -  Unwilling to sign the consent form approved by the Institutional Review Board (IRB) of
             the New York Eye and Ear Infirmary

          -  Self-reported poor compliance to treatment

          -  Reluctance to return for scheduled follow-up visits

          -  Patients not able to understand the nature of the study