Evaluation of the ototoxicity potential of once-daily, single-entity hydrocodone in patients with chronic pain: Results of two phase-3 clinical studies

Kathleen Campbell, J. Walter Kutz, Angela Shoup, Warren Wen, Shau Yu Lynch, Ellie He, Steven R. Ripa

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: 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. Objective: In this report, we aimed to evaluate the potential ototoxicity of a novel, singleentity, once-daily, extended-release hydrocodone tablet (Hysingla® ER; HYD). Study Design: Clinical study. Setting: Audiology clinics in US. Methods: 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 boneconduction 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 Results: 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. Conclusion: No ototoxic signal was observed for single-entity hydrocodone tablets at the dosages and treatment durations investigated.

Original languageEnglish (US)
Pages (from-to)E183-E193
JournalPain Physician
Volume20
Issue number1
StatePublished - Jan 1 2017

Fingerprint

Hydrocodone
Chronic Pain
Air
Audiology
Audiometry
Tablets
Hearing
Placebos
Acoustic Impedance Tests
Pure-Tone Audiometry
Low Back Pain
Hearing Loss
Opioid Analgesics
Clinical Studies
Quality of Life
Safety

Keywords

  • Audiologic monitoring
  • Clinical trials
  • Hydrocodone
  • Opioids
  • Ototoxicity monitoring
  • Sensorineural hearing loss

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Evaluation of the ototoxicity potential of once-daily, single-entity hydrocodone in patients with chronic pain : Results of two phase-3 clinical studies. / Campbell, Kathleen; Kutz, J. Walter; Shoup, Angela; Wen, Warren; Lynch, Shau Yu; He, Ellie; Ripa, Steven R.

In: Pain Physician, Vol. 20, No. 1, 01.01.2017, p. E183-E193.

Research output: Contribution to journalArticle

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abstract = "Background: 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. Objective: In this report, we aimed to evaluate the potential ototoxicity of a novel, singleentity, once-daily, extended-release hydrocodone tablet (Hysingla{\circledR} ER; HYD). Study Design: Clinical study. Setting: Audiology clinics in US. Methods: 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 boneconduction 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 Results: 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. Conclusion: No ototoxic signal was observed for single-entity hydrocodone tablets at the dosages and treatment durations investigated.",
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