Study to Determine the Effect of Azasite on Corneal Surface Irregularity

A Randomized, Double-Blind, Placebo-Controlled Study to Determine the Effect of Azasite on Corneal Surface Irregularity in Subjects With Meibomian Gland Dysfunction

The purpose of this study is to evaluate the effect of Azasite on patients with corneal surface irregularity (meibomian gland dysfunction).

Study Overview

• Status: Withdrawn
• Conditions: Meibomian Gland Dysfunction
• Intervention / Treatment: Drug: Azasite

Detailed Description

This will be a single-center, randomized, vehicle-controlled, double-masked, clinical trial comparing a four week course of Azasite (azithromycin ophthalmic 1%) to vehicle (Durasite®) in patients with MGD-related evaporative dry eye. All patients will be evaluated at screening, baseline, two weeks, four weeks, and six weeks.

The primary outcome measure will be improvement, as compared to baseline, in corneal irregularity as measured by a topographically-derived value, the Corneal Irregularity Measurement (CIM). Secondary outcome measures will be a global symptom score, tear film break up time, meibomian gland secretion characteristics, best-corrected distance visual acuity, corneal staining, axial topography based astigmatism patterns, and IOL Master keratometry.

We will enroll 60 eyes of 30 patients, and each patient will be randomly assigned to receive Azasite in one eye and vehicle (Durasite®) in the fellow eye.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19148
      • Philadelphia Eye Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to provide informed consent prior to enrollment in study
• Patient ability to follow study instructions and comply with all study protocols
• Corneal irregularity measurement (CIM) > 1.7 in both eyes
• Non-atrophic meibomian gland dysfunction (MGD) as defined by abnormal meibomian expression in at least 2 meibomian glands of the eyelids of each eye
• At least two symptoms of at least moderate severity (≥ grade 2, 0 to 3 scale) as defined in the MGD Global Symptom Score (Itching, Foreign-body sensation, Dryness, Burning, Lid swelling)
• Tear film break up time < 10 seconds
• Schirmer with anesthesia > 5 mm
• Best corrected distance visual acuity (BCDVA) > 20/100

Exclusion Criteria:

• Cicatricial or atrophic meibomian gland dysfunction (MGD)
• Any corneal disease or scar involving the central 6 mm, including epithelial basement membrane dystrophy, Salzmann nodular degeneration, recurrent erosions, keratoconus or ectasia
• Use of azithromycin or doxycycline within 1 month of screening
• Topical ocular antibiotic, anti-histamines, allergy, or steroid medication within 2 weeks of baseline (a 2 week washout after screening will be allowed)
• Topical prostaglandin analogue use within 30 days of study
• The anticipated use of any drops, gels or ointments during the study period outside of the study protocol
• Use of eye make-up during study period
• Active ocular infection or inflammation
• History of herpetic eye disease or neurotrophic keratitis
• Lid pathology (except MGD or blepharitis) that the examiner feels may affect the ocular surface
• Significant conjunctival scars (ex. h/o SJS)
• Pterygium
• Lacrimal punctal occlusion within 2 months of screening
• Ocular surgery within 1 year of screening
• Monocular patients
• Pregnant, breast-feeding, or sexually active females not using contraception
• Uncontrolled systemic disease
• Presence of any disease (medical or ocular) that, in the opinion of the investigator, may interfere with the study's safety or interpretation
• Known allergy to the study medication or its components
• Current enrollment in an investigational drug or device study within 30 days of screening for this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment eye; Azasite (azithromycin ophthalmic 1%) twice a day for 2 days followed by nightly for 4 weeks	Drug: Azasite; Patients will be given 1 drop twice a day for 2 days followed by 1 drop nightly for 4 weeks.; Other Names: Azithromycin ophthalmic 1%
Placebo Comparator: Durasite; Vehicle of Azasite used as placebo	Drug: Azasite; Patients will be given 1 drop twice a day for 2 days followed by 1 drop nightly for 4 weeks.; Other Names: Azithromycin ophthalmic 1%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Corneal Irregularity Measurement	Topographically defined corneal smoothness as compared to baseline measurement at day 0	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global symptoms score	0-3 score of itching, foreign body sensation, dryness, burning and swelling as compared to baseline measurement at day 0	2,4 and 6 weeks
Meibomian gland secretion characteristics	Meibum secretions of the eyelids will be assessed at each visit by pressing on the lower or upper lid (with a finger) until excretions are seen from at least 2 meibomian glands. The following scale, based on a scale in a study by Mathers et al (Mathers et al. Meibomian Gland Dysfunction in Chronic Blepharitis. Cornea .1991;10(4): 277-285.) will be used: NE= <2 glands expressible = Atrophic or Cicatricial MGD (exclusion at Visit 1 and 2) 0= clear secretion (normal); opaque secretion with normal viscosity; opaque secretion with increased viscosity; severely thickened secretion, toothpaste consistency At each time point, these characteristics will be compared to baseline at day 0.	2, 4 and 6 weeks
Best corrected distance visual acuity	as compared to baseline measurement at day 0	2, 4 and 6 weeks
Corneal staining	Using NEI industry workshop scale. Scores will be compared to baseline measurement at day 0	2, 4 and 6 weeks
Axial topography based astigmatism pattern	Patterns will be compared to baseline at day 0. All topography testing will be performed using the same machine and system, the Carl Zeiss Meditec Atlas, Model 9000, system 3.0.0.39. The topographic pattern will be reviewed by a masked investigator (masked to eye randomization), and categorized as one of the following: Normal/Symmetrical: Includes round, oval, or symmetric bowtie patterns; Asymmetric bowtie: Differentiated from symmetric bowtie by a difference between axial keratometry readings along the two lobes of >1D at points 1.5mm from the center, or a difference in the widths of the lobes of the bowties at that distance of >33%.; Irregular: Includes skewed radial axis (skewing by >20%), inferior or superior steepening (I-S asymmetry >1.2D); or a pattern that does not fit either 1 or 2 above.	2, 4 and 6 weeks
Intraocular Lens(IOL) Master Keratometry	As compared to baseline at day 0.	2, 4 and 6 weeks
Change in Corneal Irregularity Measurement	Topographically defined corneal smoothness as compared to baseline measurement at day 0	2 weeks, 6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tear film break-up time	Fluorescein break up time	2, 4 and 6 weeks

Collaborators and Investigators

• Sponsor: Philadelphia Eye Associates
• Collaborators: Merck Sharp & Dohme LLC; Thomas Jefferson University
• Investigators: Principal Investigator: Brad H Feldman, MD, Philadelphia Eye Associates

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: January 30, 2013
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (Estimate): February 22, 2013

Study Record Updates

• Last Update Posted (Estimate): September 28, 2016
• Last Update Submitted That Met QC Criteria: September 27, 2016
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Meibomian gland dysfunction
• Additional Relevant MeSH Terms: Eye Diseases; Eyelid Diseases; Meibomian Gland Dysfunction; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 40958

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO