Prevention of Opioid-Induced Nausea and Vomiting During Treatment of Moderate to Severe Acute Pain: A Randomized Placebo-Controlled Trial Comparing CL-108 (Hydrocodone 7.5 mg/Acetaminophen 325 mg/Rapid-Release, Low-Dose Promethazine 12.5 mg) with Conventional Hydrocodone 7.5 mg/Acetaminophen 325 mg

John R. Zuniga, Athena S. Papas, Stephen E. Daniels, Kyle Patrick, Derek D. Muse, Daniel Oreadi, Helen E. Giannakopoulos, Eric J. Granquist, Lawrence M. Levin, Joli C. Chou, Hilda Maibach, Bernard P. Schachtel

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

OBJECTIVES: To evaluate the prevention of opioid-induced nausea and vomiting (OINV) and the relief of moderate to severe acute pain by CL-108, a novel drug combining a low-dose antiemetic (rapid-release promethazine 12.5 mg) with hydrocodone 7.5 mg/acetaminophen 325 mg (HC/APAP) was used. METHODS: This was a multicenter, randomized, double-blind, placebo- and active-controlled multidose study. After surgical extraction of two or more impacted third molar teeth (including at least one mandibular impaction), 466 patients with moderate to severe pain (measured on a categorical pain intensity scale [PI-CAT]) were randomized to CL-108, HC/APAP, or placebo. Over the next 24 hours, patients used the PI-CAT to assess pain at regular intervals whereas nausea, vomiting, and other opioid-related side effects were also assessed prospectively. Study medications were taken every four to six hours as needed; supplemental rescue analgesic and antiemetic medications were permitted. Co-primary end points were the incidence of OINV and the time-weighted sum of pain intensity differences over 24 hours (SPID24). RESULTS: Relative to HC/APAP treatment alone, CL-108 treatment reduced OINV by 64% (P < 0.001). Treatment with CL-108 significantly reduced pain intensity compared with placebo (SPID24 = 16.2 vs 3.5, P < 0.001). There were no unexpected or serious adverse events. CONCLUSIONS: CL-108 is a safe and effective combination analgesic/antiemetic for the prevention of OINV during treatment of moderate to severe acute pain.

Original languageEnglish (US)
Pages (from-to)2528-2538
Number of pages11
JournalPain medicine (Malden, Mass.)
Volume20
Issue number12
DOIs
StatePublished - Dec 1 2019

Keywords

  • CL-108
  • Hydrocodone
  • OINV
  • Opioid-Induced Nausea/Vomiting
  • Pain
  • Promethazine

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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