Topical Azithromycin Improves Blepharitis Signs and Symptoms W.B. Trattlerc, K.L. Kuhne, R. Haquee, R.C. Zinke, K.N. Sallc and J.I. Luchsc Disclosure: Authors are: c

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Topical Azithromycin Improves Blepharitis
Signs and SymptomsW.B. Trattlerc, K.L. Kuhne,
R. Haquee, R.C. Zinke, K.N. Sallc and J.I.
Luchsc Disclosure Authors are c
Consultants e Employees of Inspire
Pharmaceuticals, Inc.
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Study Details

• Pilot study, open-label
• Multi-center (8 sites)
• Study population 76 patients with moderate to
  severe blepharitis Treatment All patients
  applied warm compresses (WC) BID patients in the
  AzaSite group applied azithromycin ophthalmic
  solution, 1 to each eye for 4 weeks (BID days 1
  2, then QD days 3-28)
• Clinical signs and symptoms were evaluated at
  baseline and compared to each visit throughout
  the study (weeks 1, 2, 3, 4 and 6)
• Lid scrubs were not allowed throughout the study
  and 2 weeks prior to the study initiation.

This study pertains to an off-label use of
AzaSite
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Inclusion/Exclusion Criteria

• Inclusion Criteria
• Age 18 years
• Clinical diagnosis of moderate to severe chronic
  blepharitis
• Clinical sign/symptom severity score of at least
  moderate (2) severity on either eyelid margin
  hyperemia or eyelid swelling, or both.
• Clinical sign severity score of at least moderate
  (2) severity on either eyelid debris or plugging
  of the meibomian glands, or both.
• Have a symptom severity score of at least
  moderate (2) on their self-reported most
  bothersome symptom at baseline and a score of at
  least moderate (2) on any other symptom
• Best corrected visual acuity of at least 0.7 as
  assessed by ETDRS

• Exclusion Criteria
• Use of eyelid scrubs within 2 weeks of Visit 1
  and for the duration of the study
• Use of mechanical therapy (warm compresses)
  within 2 weeks of Visit 1
• Unwilling to discontinue contact lens wear for
  the duration of the study
• History of ocular surface surgical intervention
  within 12 months prior to the study
• Use of any preserved topical ophthalmic
  medications at entry or during the study
• Use of topical ocular or orally administered
  antibiotics within 30 days of Visit 1 and for the
  duration of the study
• Use of topical cyclosporine within 30 days of
  Visit 1 and for the duration of the study
• Use of topical ocular steroids or NSAIDS 2 weeks
  prior to entry or during the study

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Study Design
Randomization
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Safety and Efficacy Endpoints

• Safety Measurements
• Biomicroscopy and External Eye Exam
• BCVA
• AE monitoring
• IOP
• Ophthalmoscopy
• Efficacy scores for the clinical signs/symptoms
• Total Clinical Outcome Score (summation of
  individual signs listed below 0-20 range)
• Eyelid Debris
• Eyelid Swelling
• Plugging of the meibomian gland
• Meibomian gland secretions
• Eyelid margin hyperemia
• Total Symptom Score (summation of five individual
  symptoms listed below 0-20 range)
• Foreign body sensation
• Ocular itching
• Ocular dryness
• Burning/painful eyes
• Swollen/heavy eyelids

scales for individual signs/symptoms range from
0 normal/none to 4very severe/obstructed
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Demographics Intent-to-Treat Population
Azithromycin in Combination with Warm Compresses (n33) Warm Compresses alone Total
Gender Female 58 68 63
Gender Male 42 32 37
Age Mean 58.4 yr 61.8 yr 60.1 yr
Race White 97 94 96
Race Black or African American 0 3 1
Race American Indian or Alaskan Native 0 3 1
Race Other 3 0 1
Ethnicity Hispanic or Latino 36 38 37
Ethnicity Not Hispanic or Latino 64 62 63
(n34)
(n67)
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Total Symptom Severity Score Intent-to-Treat
Population
(2 wks off tx)
summation of five individual symptoms (foreign
body sensation, ocular itching, ocular dryness,
burning/painful eyes, swollen/heavy eyelids)
0-20 range
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Total Clinical Outcome Severity Score
Intent-to-Treat Population
(2 wks off tx)
summation of individual signs (eyelid debris,
eyelid swelling, plugging of the meibomian gland,
meibomian gland secretions and eyelid margin
hyperemia) 0-20 range
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Individual Signs/Symptom Results
Intent-to-Treat Population
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Investigator-rated Global Assessment of Efficacy
Intent-to-Treat Population
Percentage of Patients Assessed by the Investigator to Have Excellent or Good Efficacy of Treatment Percentage of Patients Assessed by the Investigator to Have Excellent or Good Efficacy of Treatment Percentage of Patients Assessed by the Investigator to Have Excellent or Good Efficacy of Treatment
Azithromycin in Combination with Warm Compresses Warm Compresses Alone p - value
Week 1 44 (n32) 15 (n33) 0.008
Week 2 55 (n33) 15 (n33) lt0.001
Week 3 64 (n33) 32 (n34) 0.002
Week 4 70 (n33) 45 (n33) 0.015
Week 6 (2 weeks off tx) 70 (n33) 50 (n34) 0.042
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Safety Results

• Generally well tolerated
• 4 (11) patients in the azithromycin in
  combination with WC group had at least one AE vs.
  3 (8) patients in the WC alone group.
• The incidence of ocular AEs in the azithromycin
  in combination with WC group was 2 (5) vs 1 (3)
  patients in the WC alone group.

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Conclusions

• The results of this study indicate that
  Azithromycin ophthalmic solution, 1 in
  combination with warm compresses provides
  significant improvement over warm compresses
  alone in treating the signs and symptoms of
  blepharitis.
• The effect of Azithromycin ophthalmic solution
  appears to be rapid and is frequently observed
  after the first or second week of treatment for
  symptoms and investigator global assessments.
• The safety profile observed in this study is
  similar to that observed in the registration
  studies of Azithromycin ophthalmic solution, 1
  for the treatment of bacterial conjunctivitis