Randomized Clinical Trial of a Sustained-Exposure Ciprofloxacin for Intratympanic Injection During Tympanostomy Tube Surgery

Ann Otol Rhinol Laryngol. 2016 Feb;125(2):105-14. doi: 10.1177/0003489415599001. Epub 2015 Aug 20.

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.

Keywords: OTO-201; ciprofloxacin; culture; middle ear effusion; otitis media; otorrhea; sustained exposure; tympanostomy tube.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Child
  • Child, Preschool
  • Ciprofloxacin* / administration & dosage
  • Ciprofloxacin* / pharmacokinetics
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Monitoring / methods
  • Excipients / administration & dosage
  • Excipients / adverse effects
  • Female
  • Humans
  • Infant
  • Injection, Intratympanic
  • Intraoperative Care / methods*
  • Male
  • Middle Ear Ventilation / methods*
  • Otitis Media with Effusion* / diagnosis
  • Otitis Media with Effusion* / microbiology
  • Otitis Media with Effusion* / surgery
  • Poloxamer* / administration & dosage
  • Poloxamer* / adverse effects
  • Poloxamer* / pharmacology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Excipients
  • Poloxamer
  • Ciprofloxacin