Corneal Effects of 1.5% Levofloxacin Ophthalmic Solution (IQUIX

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Corneal Effects of 1.5 Levofloxacin Ophthalmic
Solution (IQUIX) in Humans Mark B. Abelson,
MD1,2Gail Torkildsen, MD2 Aron Shapiro2 Ingrid
Lapsa21Harvard Medical School, Schepens Eye
Research Institute, Boston, MA 2Ophthalmic
Research Associates, Inc., North Andover, MA
Financial Disclosure MB Abelson, A Shapiro, I
Lapsa are full-time employees of Ophthalmic
Research Associates, Inc.
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Study Background

• IQUIX approved for treating bacterial keratitis
• In vitro Levofloxacin least cytotoxic
  fluoroquinolone in human corneal keratocyte and
  endothelial cell cultures1
• In vivo Wound healing in rabbits and primates
  (2 drops QID x 4 days)2
• No adverse effect on cornea,
  re-epithelialization, keratocyte structure /
  organization, or wound healing

1Bezwada P et al. Curr Med Res Opin 24419-24,
2008 2Clark L et al. Cutaneous Ocular Toxicology
231-18, 2004
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Purpose

• To evaluate corneal endothelial integrity and
  morphology in humans after 2-wk intensive dosing
  regimen with 1.5 levofloxacin ophthalmic
  solution (IQUIX).

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Methods Prospective Single-Center,
Investigator-Masked Study

• Healthy human volunteers (n48)
• 224 IQUIX doses OD over 14 days
• Assessments Baseline, Day 8, Day 15, Day 21
  (7-days post-dosing)
• Safety analysis Baseline vs 7-days post-dosing

Days 1-3(27 doses/day) 1 drop OD every 30 min 8 AM 8 PM 1 drop OD at 12 AM 2 AM
Days 4-14(13 doses/day) 1 drop OD every hr 8 AM 8 PM
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Key Safety Assessments
Intensive IQUIX Dosing

• Specular microscopy
• Endothelial cell density
• Endothelial cell morphology (cell size
  variability, hexagonal cells)
• Pachymetry central corneal thickness
• Slit-lamp biomicroscopy
• Visual acuity

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Corneal Endothelial Cell Density
Intensive IQUIX Dosing
2767 317
2786 295
Density, cells / µm2, mean
Post-dosing
Baseline
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Endothelial Cell Size Coefficient of Variation
Intensive IQUIX Dosing
Coefficient of Variation, mean
31.4 5.2
31.8 5.9
Post-dosing
Baseline
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Percent Hexagonal Cellsin Corneal Endothelium
Intensive IQUIX Dosing
Percent, mean
59.8 10.8
61.9 11.3
Baseline
Post-dosing
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Corneal Thickness
Intensive IQUIX Dosing
560 36
568 46
Thickness, µm, mean
Post-dosing
Baseline
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Intensive IQUIX Dosing Summary of Findings

• No clinically significant negative changes in any
  measured safety parameter
• Endothelial cell density
• Endothelial cell morphology
• Central corneal thickness
• Visual acuity
• Slit-lamp biomicroscopy
• Intraocular pressure
• Dilated fundoscopy
• Treatment-related adverse events dysgeusia
  (30) eye irritation (7) eye pruritis (6)

Data not shown
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Intensive IQUIX Dosing Conclusion

• Intensive dosing with IQUIX (levofloxacin 1.5)
  does not adversely affect corneal endothelium