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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Drug: Topical spironolactone ophthalmic solution, 0.005 mg/cc
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: are currently pregnant have a positive result at the urine pregnancy test (Baseline/Day 0) intend to become pregnant during the study treatment period are breast-feeding 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Subjects receive topical spironolactone ophthalmic solution, 0.005 mg/cc four times a day for 4 weeks. | Drug: Topical spironolactone ophthalmic solution, 0.005 mg/cc<br>* Used four times a day in both eyes for 4 weeks.<br>|
| Placebo Comparator: Placebo<br>Subjects receive topical spironolactone vehicle as placebo four times a day for 4 weeks. | Drug: Placebo<br>* Used four times a day in both eyes for 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 4 in the Symptom Assessment Questionnaire Dry Eye (SANDE) score. | The SANDE score is calculated by taking the square root of the product of the severity of symptoms score and the frequency of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount or absence of dry eye symptoms. | Baseline to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 4 in the corneal fluorescein staining | Corneal fluorescein staining is measured by the 0-3 point National Eye Institute (NEI) grading scale in any one corneal region. 0 represents no staining and 3 represents maximal/severe staining and damages to the cornea. Scores from each of the five corneal regions as defined by the NEI grading scale will be evaluated independently. | Baseline to Week 4 |