RESUMO
UNLABELLED: Oxytrex is a novel drug that combines oxycodone with ultralow-dose naltrexone, an opioid antagonist. Ultralow-dose opioid antagonists have been demonstrated to enhance and prolong opiate analgesia and alleviate opioid tolerance and withdrawal in rodents. This 3-week, Phase II clinical trial assessed safety and analgesic efficacy of Oxytrex in patients with moderate to severe pain from osteoarthritis. Patients with a pain score > or =5 received placebo, oxycodone 4 times a day (qid), Oxytrex qid, or Oxytrex twice a day (bid). All active treatment groups received the same total daily dose and dose escalation of oxycodone starting at 10 and ending at 40 mg/day. Importantly, the Oxytrex bid group received a lower daily dose of naltrexone than Oxytrex qid (0.002 vs 0.004 mg/day). Oxytrex bid produced a 39% reduction in pain intensity, which was significantly greater than that of placebo (P < .001), oxycodone qid (P = .006), and Oxytrex qid (P = .003). Oxytrex bid was also superior to placebo in quality of analgesia (P = .002), duration of pain control each day (P = .05), patients' global assessments (P = .04), and the Western Ontario and MacMaster Universities Osteoarthritis Index total score (P = .03). The incidence of side effects was comparable between active treatments. In this Phase II dose-ranging study, Oxytrex bid demonstrated greater pain relief with a more convenient dosing schedule compared to oxycodone qid. PERSPECTIVE: Preclinical data have shown ultralow-dose opioid antagonists to enhance and prolong opioid analgesia while reducing analgesic tolerance and physical dependence. Recent molecular pharmacology data show a mechanism of action to be the prevention of aberrant G protein coupling by opioid receptors that underlies opioid tolerance and dependence.