Efficacy and Safety of Fluorometholone (FML) in Dry Eye Disease (Keratoconjunctivitis Sicca) (FML)

Randomized, Double-Masked, Vehicle-controlled Phase III Trial on the Safety/Efficacy of FML® 0.1% in the Treatment of the Inflammatory Exacerbation Provoked by Exposure to an Adverse Controlled Environment in Patients With Dry Eye Disease

Hypothesis: Fluorometholone (FML) 0.1% eyedrops topically applied 4 times a day for 22 days is more efficient than artificial tears (Liquifilm) in dry eye disease (DED) and ameliorates the worsening of the disease after exposure to an adverse controlled environment.

Study Overview

• Status: Completed
• Conditions: Dry Eye
• Intervention / Treatment: Drug: FML 0.1% eyedrops; Drug: Liquifilm artificial tears eyedrops

Detailed Description

There will be 4 visits in 3 different days:

Visit 1 (V1). Inclusion in normalized controlled environment (NCE)

Visit 2 (V2). 21 days post-treatment. Data collected in NCE

Visit 3 (V3). 21 days post-treatment. Data collected in adverse controlled environment (ACE)

Visit 4 (V4). 22 days post-treatment. Recovery visit in ACE. Data collected in NCE

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Valladolid, Spain, 47011
    • IOBA (Instituto de Oftalmobiología Aplicada), University of Valladolid
  • Valladolid, Spain, 47011
    • IOBA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years
• Signed informed consent
• Subjects refer worsening in their pathologies when exposed to adverse environmental conditions in their daily life
• Fluorescein corneal staining ≥ 1in Oxford Scale
• Ocular surface disease index (OSDI) test > 12
• Tear breakup Time (TBT) ≤ 7 seconds in both eyes
• Schirmer test without anesthesia ≤ 10 mm in 5 minutes in both eyes
• Any concomitant medication that may affect dry eye syndrome, ocular surface or vision, must have started at least 3 months before screening visit, and there are no changes in dose expected during the study duration.
• Best corrected visual acuity at least 0.1 logMar at 6 meters with both eyes
• Current use of ophthalmic artificial tears at study inclusion.
• Signed informed consent
• Signed data protection consent

Exclusion Criteria:

• Sensitivity or known intolerance to any of the products used in the study
• Previous severe ocular inflammation or infections in the 6 previous months to study inclusion
• Any ocular pathology other than dry eye syndrome or atopic keratoconjunctivitis
• Any ocular surgery or trauma that may affect corneal sensitivity and / or normal tear distribution (refractive or cataract surgery) in the 6 previous months or any ocular or systemic surgery planned during the study duration that may affect the study as assessed by principal investigator.
• Use of contact lenses in the 3 previous months to study inclusion
• Use of any topical medication for pathologies other than dry eye syndrome.
• Any ocular topical treatment for dry eye syndrome with corticosteroids or non steroid anti-inflammatory drugs must have stopped 1 month before study inclusion. Any treatment with topical cyclosporin must have been stopped 3 months before study inclusion.
• Any uncontrolled severe systemic disease that may affect the eye (except for Sjögren Syndrome)
• Start, discontinuation or dose change during the study of antihistaminic, cholinergic agents, beta blockers, antidepressants or any other systemic medications with potential effect over tear film.
• Start of any systemic treatment that may affect dry eye syndrome, vision, ocular surface or intraocular pressure during the 3 previous months to study inclusion.
• Surgical / non surgical tear point occlusion in the 3 previous months to study inclusion or prevision during study duration for this procedure.
• Cup / disc ratio > 0.6
• History of intraocular pressure > 22 mm Hg within 2 months previous to study inclusion
• Pregnancy or breastfeeding women
• Inclusion in another research study in the previous 30 days to study inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FML 0.1% eyedrops; FML (fluorometholone) 0.1% eyedrops 4 times a day in both eyes for 22 days	Drug: FML 0.1% eyedrops; Ocular topical application of fluorometholone 0.1% 4 times a day during 22 days; Other Names: 0.1% fluorometholone
Active Comparator: Liquifilm artificial tears eyedrops; Topical application 4 times a day in both eyes for 22 days	Drug: Liquifilm artificial tears eyedrops; Liquifilm instillation 4 times a day for 22 days; Other Names: Artificial tears

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluorescein corneal staining	Evidence of statistically significant changes in the number of subjects with an increase ≥ 1 point in fluorescein corneal staining between pre and post adverse condition exposure in ACE (V2 vs V3) and between post adverse condition exposure in ACE and recovery visit (V3 vs V4).	22 days
Symptom Assessment in Dry Eye (SANDE) I and II questionnaire	Evidence of statistically significant changes in the number of subjects with a reduction ≥ 2 points in SANDE score between pre and post adverse condition exposure in ACE (V2 vs V3) and between post adverse condition exposure and recovery visit (V3 vs V4).	22 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tear inflammatory molecule levels	Evidence of statistically significant changes between the differences in tear molecule concentrations pre and post adverse condition exposure (V2 vs V3) in ACE and between post adverse condition exposure and recovery visit (V3 vs V4).	22 days
Best corrected visual acuity	Best corrected visual acuity measured with the ETDRS (Eearly Treatment for Diabetes Retinopathy Study) chart after 22 days of treatment compared to baseline	22 days
Biomicroscopy findings at slit lamp examination	Biomicroscopy findings (general aspect of ocular surface and anterior segment, plus corneal and conjunctival staining) after 22 days of treatment compared to baseline	22 days
Adverse events during the trial	Adverse events that occur during the trial	22 days
Other Efficacy Measures	Conjunctival Staining (Lissamine Green; Oxford Scale) T-BUT (tear break-up time) Conjunctival hyperemia (Efron Scale) Patient satisfaction with the treatment (VAS 0-100)	22 days
Intraocular pressure (IOP) and fundus examination	Intraocular pressure levels measured with a Goldman tonometer Evaluation of optic disk/cup ratio at fundus examination	22 days

Collaborators and Investigators

• Sponsor: Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA
• Investigators: Principal Investigator: Margarita Calonge-Cano, MD, PhD, Ocular surface group Director - IOBA

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: January 22, 2014
• First Submitted That Met QC Criteria: January 29, 2014
• First Posted (Estimate): January 31, 2014

Study Record Updates

• Last Update Posted (Estimate): January 8, 2015
• Last Update Submitted That Met QC Criteria: January 7, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: dry eye; steroids; dry eye disease; keratoconjunctivitis sicca; dry eye syndrome
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratoconjunctivitis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Allergic Agents; Pharmaceutical Solutions; Ophthalmic Solutions; Lubricant Eye Drops; Fluorometholone
• Other Study ID Numbers: IOBA-CERLAB-003-2013