title: Safety and tolerability of loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension in pediatric subjects.
abstract: BACKGROUND
  Loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension (LE/T) is indicated for steroid-responsive inflammatory ocular conditions where superficial bacterial ocular infection or a risk of bacterial ocular infection exists. LE/T was shown to be safe in healthy volunteers and patients aged 18 years and older with minimal effect on intraocular pressure (IOP).
  
  
  OBJECTIVE
  The aim of the study was to evaluate the safety of LE/T in pediatric subjects by examining data from two clinical studies.
  
  
  METHODS
  Two randomized, multicenter, double-masked, parallel-group (one two-arm, the other four-arm) studies were conducted in subjects aged 0-6 years (N = 245). One study assessed LE/T compared with vehicle in the management of lid inflammation (n = 108) and the other compared LE/T with loteprednol etabonate ophthalmic suspension 0.5% (LE), tobramycin ophthalmic solution 0.3% (tobramycin), and vehicle in the treatment of blepharoconjunctivitis (n = 137). In the first study, subjects were randomized to LE/T or vehicle administered four times daily (qid) for the first 7 days followed by twice daily (bid) for 7 days along with warm compresses bid for the entire 2 weeks. In the second study, subjects were randomized to LE/T, LE, tobramycin, or vehicle administered qid for 14 days. Treatment-emergent ocular and non-ocular adverse events (AEs) and bilateral vision were assessed at all study visits in both studies. In addition, in the lid inflammation study, IOP was assessed at all visits. The primary safety endpoint in both studies was the incidence of treatment-emergent AEs.
  
  
  RESULTS
  The incidence of LE/T treatment-emergent AEs was low. A total of four ocular AEs were reported for three LE/T-treated subjects in the first study (conjunctivitis [two events], meibomian gland dysfunction, and corneal staining), and one ocular AE was reported for an LE/T-treated subject in the second study (eye pain). A total of 13 non-ocular AEs were reported for eight LE/T-treated subjects in the two trials. The most prevalent non-ocular AEs were pyrexia (three events) and rash (two events). There were no differences in the incidence of specific ocular and non-ocular AEs between the LE/T group and the comparator treatment group. In both studies, there were no clinically meaningful reductions in vision at follow-up visits. Mean IOP and IOP changes from baseline, assessed in the lid inflammation study, were not different between LE/T and vehicle treatment groups at any study visits.
  
  
  CONCLUSIONS
  The results of these two clinical trials demonstrate the short-term safety of treatment with topical LE/T in pediatric subjects (0-6 years of age) with lid inflammation or blepharoconjunctivitis.
authors.affiliation: Global Pharmaceuticals, Bausch Lomb, Inc., Rochester, NY 14609, USA. tcomstock@bausch.com
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Comstock
authors.forename: Michael R
authors.initials: MR
authors.lastname: Paterno
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Bateman
authors.forename: Heleen H
authors.initials: HH
authors.lastname: Decory
authors.forename: Matthew
authors.initials: M
authors.lastname: Gearinger
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects*; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003231:Conjunctivitis / Q000139:chemically induced*; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000209:etiology; D005143:Eyelids / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000139:chemically induced; D007429:Intraocular Pressure / Q000187:drug effects; D000069559:Loteprednol Etabonate; D008297:Male; D015337:Multicenter Studies as Topic; D009883:Ophthalmic Solutions / Q000009:adverse effects; D012449:Safety; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects*; D014785:Vision, Ocular / Q000187:drug effects; D014792:Visual Acuity / Q000187:drug effects
chemical_list: D000730:Androstadienes; D018926:Anti-Allergic Agents; D000900:Anti-Bacterial Agents; D009883:Ophthalmic Solutions; D014031:Tobramycin; D000069559:Loteprednol Etabonate