(431) Efficacy of CL-108 compared to hydrocodone 7.5 mg/acetaminophen 325 mg in preventing vomiting and the use of anti-emetics, Opioid-Induced Nausea and Vomiting (OINV)

Abstract

CL-108 (containing hydrocodone 7.5 mg, acetaminophen 325 mg [HC/APAP] with fast-release promethazine 12.5 mg) was formulated to provide analgesia and prevent opioid-induced nausea and vomiting (OINV). CL-108 has been shown to be an effective analgesic compared to placebo and to significantly reduce the incidence of moderate/severe nausea and vomiting and the use of anti-emetics compared to HC/APAP.1 Another definition of OINV includes only two criteria: any vomiting or use of anti-emetics. Because this objective definition is also used to determine the efficacy of a drug in preventing OINV, we used this 2-component endpoint to analyze the results of this study. After surgical extraction of at least 2 impacted molar teeth, 466 patients with moderate-to-severe pain were randomized to self-administer CL-108 (n=211), HC/APAP (n=205), or placebo (n=50) every 4–6 hours as needed for pain. On an hourly basis (while awake) over the first 24 post-op hours patients documented the intensity of pain and nausea and, importantly, the frequency of vomiting and use(s) of an antiemetic. There was 52% less risk of vomiting for patients who used CL-108 compared to HC/APAP-treated patients, who used more doses of anti-emetics than CL-108-treated patients (all p<0.001). HC/APAP-treated patients also used anti-emetics earlier (and more repeated doses) than CL-108-treated patients (p<0.001). Applying the stringent 2-component definition of OINV to these 24-hour results: patients who used CL-108 experienced significantly less OINV than patients who used HC/APAP, representing 64% relative reduction in the risk of developing OINV (p<0.001). We conclude that CL-108 has a substantive effect on the risk of developing of OINV, less than a standard treatment for moderate-to-severe pain that contains the same dosages of hydrocodone and acetaminophen. (1. Schachtel B, et al. J Pain. 2014.) Sponsored by Charleston Laboratories and Daiichi Sankyo.