title: Randomized Clinical Trial of a Sustained-Exposure Ciprofloxacin for Intratympanic Injection During Tympanostomy Tube Surgery.
abstract: OBJECTIVE
  This exploratory clinical trial evaluated the safety and clinical activity of a novel, sustained-exposure formulation of ciprofloxacin microparticulates in poloxamer (OTO-201) administered during tympanostomy tube placement in children.
  
  
  METHODS
  Double-blind, randomized, prospective, placebo- and sham-controlled, multicenter Phase 1b trial in children (6 months to 12 years) with bilateral middle ear effusion requiring tympanostomy tube placement. Patients were randomized to intraoperative OTO-201 (4 mg or 12 mg), placebo, or sham (2:1:1 ratio).
  
  
  RESULTS
  Eighty-three patients (52 male/31 female; mean age, 2.80 years) were followed for safety (otoscopic exams, cultures, audiometry, and tympanometry) and clinical activity, defined as treatment failure (physician-documented otorrhea and/or otic or systemic antibiotic use ≥3 days post surgery). At baseline, 14.3% to 36.8% of children showed positive cultures of middle ear effusion samples in at least 1 ear. Through day 15, treatment failures accounted for 14.3%, 15.8%, 45.5%, and 42.9% of patients (OTO-201 4 mg, OTO-201 12 mg, placebo, and sham, respectively); treatment failure reductions for OTO-201 doses were significant compared to pooled control (P values = .023 and .043, respectively). Observed OTO-201 safety profile was indistinguishable from placebo or sham.
  
  
  CONCLUSIONS
  Results of this first clinical trial suggest that OTO-201 was well tolerated and shows preliminary clinical activity in treating tympanostomy tube otorrhea.
authors: Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA emair@ceenta.com.
authors: Eric A
authors: EA
authors: Mair
authors: Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA.
authors: Jonathan R
authors: JR
authors: Moss
authors: Children's Hospital of Pittsburgh, UPMC, Pittsburgh, Pennsylvania, USA.
authors: Joseph E
authors: JE
authors: Dohar
authors: Department of Otolaryngology, University of Florida, Gainesville, Florida, USA.
authors: Patrick J
authors: PJ
authors: Antonelli
authors: Forsythe and Bear, LLC, Woodland Hills, California, USA.
authors: Moraye
authors: M
authors: Bear
authors: Otonomy, Inc, San Diego, California, USA.
authors: Carl
authors: C
authors: LeBel
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D005079:Excipients / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D000069555:Injection, Intratympanic; D007430:Intraoperative Care / Q000379:methods*; D008297:Male; D008876:Middle Ear Ventilation / Q000379:methods*; D010034:Otitis Media with Effusion / Q000175:diagnosis / Q000382:microbiology / Q000601:surgery; D020442:Poloxamer / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D020442:Poloxamer; D002939:Ciprofloxacin
keywords: OTO-201; ciprofloxacin; culture; middle ear effusion; otitis media; otorrhea; sustained exposure; tympanostomy tube