BACKGROUND: Prescription opioids have substantial abuse potential. This study compared the positive subjective drug effects of a newly developed extended-release (ER) oxycodone (OC)/acetaminophen (acetyl-para-aminophenol [APAP]) formulation with those of immediate-release (IR) OC/APAP. METHODS: This randomized, double-blind, active- and placebo-controlled, 7-way crossover study enrolled healthy volunteers who were recreational prescription opioid users. The protocol was approved by an institutional review board and all participants provided written informed consent. Participants received single doses of intact ER and IR OC/APAP 15/650 mg, intact ER and IR OC/APAP 30/1300 mg, crushed ER and IR OC/APAP 30/1300 mg, and placebo. Peak subjective effects (Emax), time to Emax, and area under the drug-effect curves for drug liking, drug high, and good drug effects were measured using visual analogue scales. Least squares means with 95% confidence interval were compared using analysis of variance. RESULTS: Among completers (N = 55), intact ER OC/APAP produced delayed and lower peak effects versus IR OC/APAP. Comparing intact tablets, the drug liking Emax (least squares means [95% confidence interval]) was significantly lower for OC/APAP 30/1300 mg (76.4 [72.8 to 80.0]) than for IR OC/APAP 30/1300 mg (85.6 [81.9 to 89.2]; difference, -9.2 [-13.1 to -5.2]; P < 0.001). Similar results were observed for intact ER and IR OC/APAP (15 mg/650 mg). Crushing ER OC/APAP 30/1300 mg further delayed these effects compared with the same dose of crushed IR OC/APAP and intact ER OC/APAP. CONCLUSIONS: Extended-release OC/APAP produced lower subjective drug effects than IR OC/APAP. Crushing ER OC/APAP further delayed onset of subjective effects compared with intact ER OC/APAP. The ER OC/APAP may be less attractive for abuse than IR OC/APAP. CLINICAL TRIAL REGISTRATION: This phase 1 study conducted in the United States was not registered.
RCT Entities:
BACKGROUND: Prescription opioids have substantial abuse potential. This study compared the positive subjective drug effects of a newly developed extended-release (ER) oxycodone (OC)/acetaminophen (acetyl-para-aminophenol [APAP]) formulation with those of immediate-release (IR) OC/APAP. METHODS: This randomized, double-blind, active- and placebo-controlled, 7-way crossover study enrolled healthy volunteers who were recreational prescription opioid users. The protocol was approved by an institutional review board and all participants provided written informed consent. Participants received single doses of intact ER and IR OC/APAP 15/650 mg, intact ER and IR OC/APAP 30/1300 mg, crushed ER and IR OC/APAP 30/1300 mg, and placebo. Peak subjective effects (Emax), time to Emax, and area under the drug-effect curves for drug liking, drug high, and good drug effects were measured using visual analogue scales. Least squares means with 95% confidence interval were compared using analysis of variance. RESULTS: Among completers (N = 55), intact ER OC/APAP produced delayed and lower peak effects versus IR OC/APAP. Comparing intact tablets, the drug liking Emax (least squares means [95% confidence interval]) was significantly lower for OC/APAP 30/1300 mg (76.4 [72.8 to 80.0]) than for IR OC/APAP 30/1300 mg (85.6 [81.9 to 89.2]; difference, -9.2 [-13.1 to -5.2]; P < 0.001). Similar results were observed for intact ER and IR OC/APAP (15 mg/650 mg). Crushing ER OC/APAP 30/1300 mg further delayed these effects compared with the same dose of crushed IR OC/APAP and intact ER OC/APAP. CONCLUSIONS: Extended-release OC/APAP produced lower subjective drug effects than IR OC/APAP. Crushing ER OC/APAP further delayed onset of subjective effects compared with intact ER OC/APAP. The ER OC/APAP may be less attractive for abuse than IR OC/APAP. CLINICAL TRIAL REGISTRATION: This phase 1 study conducted in the United States was not registered.
Authors: Sherri Rauenzahn; Adam Sima; Brian Cassel; Danielle Noreika; Teny Henry Gomez; Lynn Ryan; Carl E Wolf; Luke Legakis; Egidio Del Fabbro Journal: Support Care Cancer Date: 2017-01-25 Impact factor: 3.603
Authors: Stefania Chiappini; Rachel Vickers-Smith; Amira Guirguis; John M Corkery; Giovanni Martinotti; Daniel R Harris; Fabrizio Schifano Journal: Pharmaceuticals (Basel) Date: 2022-05-27