(436) Opioid-induced nausea and vomiting (OINV) in post-operative patients: a comparison of CL-108 to hydrocodone 7.5 mg/acetaminophen 325 mg

Abstract

OINV is a common pharmacologic side effect of opioids which patients often describe as more annoying than pain. CL-108, consisting of hydrocodone 7.5mg/ acetaminophen 325mg (HC/APAP) with rapid-release promethazine 12.5mg, is an analgesic being developed for the relief of moderate-to-severe pain and the prevention of OINV. An oral surgery study1 demonstrated the efficacy of CL-108 over 24 hours for pain compared to placebo and for OINV compared to HC/APAP (both p<0.001). To study CL-108 over 48 hours, a randomized, double-blind, phase III trial evaluated pain intensity reduction by CL-108 compared to placebo and the incidence of OINV compared to HC/APAP in patients following orthopedic surgery. To improve assay sensitivity, the study population was enriched by identifying patients with a history suggestive of being likely to develop nausea. After undergoing primary unilateral first metatarsal bunionectomy, 552 patients rated pain intensity on a categorical scale. If they had moderate or severe pain confirmed on a 0-10 numerical pain intensity rating scale (PI-NRS) patients were randomized to CL-108, HC/APAP, or placebo under double-blind conditions. They used the PI-NRS at regular intervals over 48 hours while documenting the presence, severity, and frequency of nausea, retching, and vomiting. Patients remedicated every 4-6 hours and took antiemetic and supplementary (rescue) analgesic medications as needed. The co-primary endpoints were SPID48 (for analgesia) and a composite OINV prevention endpoint (no vomiting or use of antiemetic over 48 hours). Patients who used CL-108 had significant pain relief compared to placebo and 74% reduction in the risk of developing OINV relative to patients who used HC/APAP (both p<0.001), with NNT of 4. There were no unexpected or serious side effects. We conclude that CL-108 is a safe and effective analgesic for moderate-to-severe pain and the prevention of OINV. (1. Schachtel, B J Pain. 2014.) Sponsored by Charleston Laboratories and Daiichi Sankyo.