Transcript Asbell ASCRS Presentation 2007
Corneal Effects of 1.5% Levofloxacin Ophthalmic Solution (IQUIX
®
) in Humans
Mark B. Abelson, MD 1,2 Gail Torkildsen, MD 2 ; Aron Shapiro 2 ; Ingrid Lapsa 2 1 Harvard Medical School, Schepens Eye Research Institute, Boston, MA 2 Ophthalmic Research Associates, Inc., North Andover, MA Financial Disclosure: MB Abelson, A Shapiro, I Lapsa are full-time employees of Ophthalmic Research Associates, Inc.
Study Background
IQUIX ® approved for treating bacterial keratitis In vitro: Levofloxacin least cytotoxic fluoroquinolone in human corneal keratocyte and endothelial cell cultures 1 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 1 Bezwada P et al. Curr Med Res Opin 24:419-24, 2008 2 Clark L et al. Cutaneous Ocular Toxicology 23:1-18, 2004
Purpose
To evaluate corneal endothelial integrity and morphology in humans after 2-wk intensive dosing regimen with 1.5% levofloxacin ophthalmic solution (IQUIX ® ).
Methods: Prospective Single-Center, Investigator-Masked Study
Healthy human volunteers (n=48) 224 IQUIX ® doses OD over 14 days Days 1-3 (27 doses/day) Days 4-14 (13 doses/day) 1 drop OD every 30 min 8 AM – 8 PM 1 drop OD at 12 AM & 2 AM 1 drop OD every hr 8 AM – 8 PM Assessments: Baseline, Day 8, Day 15, Day 21 (7-days post-dosing) Safety analysis: Baseline vs 7-days post-dosing
Intensive IQUIX ® Dosing
Key Safety Assessments
Specular microscopy Endothelial cell density Endothelial cell morphology (cell size variability, % hexagonal cells) Pachymetry: central corneal thickness Slit-lamp biomicroscopy Visual acuity
Intensive IQUIX ® Dosing
Corneal Endothelial Cell Density
3500 3000 2500 2000 1500 1000 500 0
2767 ± 317 2786 ± 295 Baseline Post-dosing
Intensive IQUIX ® Dosing
Endothelial Cell Size: Coefficient of Variation
20 10 0 50 40 30
31.4
± 5.2
31.8
± 5.9
Baseline Post-dosing
Intensive IQUIX ® Dosing
Percent Hexagonal Cells in Corneal Endothelium
100 80 60 40 20 0
59.8
± 10.8 61.9
± 11.3
Baseline Post-dosing
Intensive IQUIX ® Dosing
Corneal Thickness
700 600 500 400 300 200 100 0
560 ± 36 568 ± 46 Baseline Post-dosing
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
Intensive IQUIX
®
Dosing: Conclusion
Intensive dosing with IQUIX ® (levofloxacin 1.5%) does not adversely affect corneal endothelium