The Effects and Safety of Topical Spironolactone Ophthalmic Solution, 0.005 mg/cc in Subjects With Dry Eye Disease

A Single-Center, Prospective Randomized, Double-Masked, Placebo-Controlled, Parallel- Group Pilot Study of the Effects and Safety of Topical Spironolactone Ophthalmic Solution, 0.005 mg/cc in Subjects With Dry Eye

The objective of this study is to evaluate the clinical efficacy of topical spironolactone ophthalmic solution, 0.005 mg/cc in subjects with dry eye disease compared to placebo. The hypothesis for this study is that topical spironolactone ophthalmic solution will be beneficial in the management of signs and symptoms of dry eye disease when compared to placebo.

Inclusion Criteria:

• SANDE questionnaire ≥30 mm
• Schirmer test without anesthesia ≥2 mm/5 minutes
• Corneal fluorescein staining score of ≥1 (0-3 point scale) in at least 1 corneal region of the 5 zones based on the NEI scale, with particular attention paid to the inferior region
• The same eye (eligible eye) must fulfill all the above criteria
• No lagophthalmos, entropion, ectropion
• No significant conjunctivochalasis (graded <2 on a 0-4 point scale)
• Best corrected distance visual acuity (BCDVA) score of +0.7 or better as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) (20/200 Snellen value) in both eyes at the baseline visit
• Intraocular pressure of ≥10 to <21 mmHg
• If a female of childbearing potential, have a negative pregnancy test
• Only patients who satisfy all Informed Consent requirements may be included in the study
• The patient must read, sign and date the Informed Consent document before any study related procedures are performed
• The Informed Consent form signed by patients must have been approved by the Institutional Review Board (IRB) / Independent Ethics Committee (IEC) for the current study
• Patients must have the ability and willingness to comply with study procedures
• Ability to speak and understand the English language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments

Exclusion Criteria:

• Evidence of an active ocular infection, in either eye

• Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study

• History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye

• Intraocular inflammation defined as Tyndall score >0

• Systemic disease not stabilized within 1 month before Visit 1 (e.g. diabetes with glycemia out of range, thyroid malfunction) or judged by the investigator to be incompatible with the study (e.g. current systemic infections) or incompatible with the frequent assessment required by the study

• Patient had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or had a clinically significant allergy to drugs, foods, amide local anesthetics, or other materials including commercial artificial tears that is judged by the investigator to be incompatible with the study

• Females of childbearing potential (those who are not surgically sterilized or post- menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:

  1. are currently pregnant
  2. have a positive result at the urine pregnancy test (Baseline/Day 0)
  3. intend to become pregnant during the study treatment period
  4. are breast-feeding
  5. are not willing to use highly effective birth control measures, such as: hormonal contraceptives - oral, implanted, transdermal, or injected - and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or Intra Uterine Device (IUD) - during the entire course of and 30 days after the study treatment period ends

• Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being

• Use of topical, nasal, or oral antihistamine within 24 hours prior to or during study enrollment

• Use of oral spironolactone within 6 months prior to or during study enrollment

• Previous use of topical spironolactone ophthalmic solution

• Unstable use of topical cyclosporine, topical corticosteroids, artificial tears, lid scrubs, or any other topical drug for the treatment of dry eye in either eye prior to and during study enrollment

• Contact lenses use at any time 30 days prior or during study enrollment

• Cauterization of the punctum or punctal plugs placed within 14 days prior or during study enrollment

• Any prior ocular surgery (including refractive palpebral and cataract surgery) within 90 days of study enrollment

• History of drug addiction or alcohol abuse

• Participation in a trial with a new active substance during the past 6 months

• Participation in another trial study at the same time as the present study

• Have been exposed to any investigational drug within the preceding 30 days