title: Evaluation of the Ototoxicity Potential of Once-Daily, Single-Entity Hydrocodone in Patients with Chronic Pain: Results of Two Phase-3 Clinical Studies.
abstract: Use/misuse of the opioid combination hydrocodone-acetaminophen has been associated with permanent hearing loss. Although reports have been rare, this potential effect can have significant detrimental effect on patients' overall quality of life. To date, the ototoxic effect of hydrocodone alone has not been systematically investigated.
  
  
  
  In this report, we aimed to evaluate the potential ototoxicity of a novel, single-entity, once-daily, extended-release hydrocodone tablet (Hysingla® ER; HYD).
  
  
  
  Clinical study.
  
  
  
  Audiology clinics in US.
  
  
  
  Results from 1207 patients in two phase 3 clinical studies were evaluated: A placebo-controlled study with an enriched enrollment, randomized withdrawal design in patients with chronic low back pain, and an open-label, long-term, safety study in patients with chronic nonmalignant and non-neuropathic pain. Comprehensive audiologic assessments (comprising pure-tone air-conduction audiometry in the conventional [0.25-8 kHz] and ultra-high [10-16 kHz] frequencies, pure-tone bone-conduction audiometry, tympanometry, speech reception thresholds, and word recognition) were conducted at baseline and end-of-studies; air-conduction audiometry was conducted periodically during the studies. All audiologic assessments were performed in audiology clinics in the United States by licensed audiologists. The primary endpoint was changes from baseline in pure-tone air-conduction thresholds in the conventional frequencies during the studies. These trials are registered with ClinicalTrials.gov, identifiers NCT01400139 and NCT01452529.
  
  
  
  During the studies, mean changes from baseline in air-conduction thresholds were clinically unremarkable. Bidirectional variability across all test frequencies was observed; 82% of patients did not experience significant threshold changes during the studies, 7% had potential hearing decrement, and 10% experienced hearing sensitivity improvement. No notable differences were observed between patients receiving HYD and placebo or between different HYD doses.
  
  
  
  No ototoxic signal was observed for single-entity hydrocodone tablets at the dosages and treatment durations investigated. Key words: Audiologic monitoring, clinical trials, hydrocodone, opioids, ototoxicity monitoring, sensorineural hearing loss.
authors.affiliation: Audiology Consultant, Glenarm, IL.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Campbell
authors.affiliation: Otolaryngology Consultant, Dallas, TX.
authors.forename: J Walter
authors.initials: JW
authors.lastname: Kutz
authors.affiliation: Audiology Consultant, Dallas, TX.
authors.forename: Angela
authors.initials: A
authors.lastname: Shoup
authors.affiliation: Purdue Pharma L.P., Stamford, CT.
authors.forename: Warren
authors.initials: W
authors.lastname: Wen
authors.affiliation: Purdue Pharma L.P., Stamford, CT.
authors.forename: Shau Yu
authors.initials: SY
authors.lastname: Lynch
authors.affiliation: Purdue Pharma L.P., Stamford, CT.
authors.forename: Ellie
authors.initials: E
authors.lastname: He
authors.affiliation: Purdue Pharma L.P., Stamford, CT.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ripa
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D059350:Chronic Pain / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000627:therapeutic use; D017116:Low Back Pain / Q000188:drug therapy* / Q000523:psychology; D011788:Quality of Life
chemical_list: D000701:Analgesics, Opioid; D006853:Hydrocodone