Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a randomized, controlled trial of Oxytrex.
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.


CONCLUSIONS
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.
Chindalore
Vishala L
VL
Anniston Medical Clinic, Anniston, Alabama, USA.
Craven
Richard A
RA
Yu
K Peony
KP
Butera
Peter G
PG
Burns
Lindsay H
LH
Friedmann
Nadav
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000698:Analgesia / Q000379:methods*; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D010003:Osteoarthritis / Q000188:drug therapy; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D017060:Patient Satisfaction; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D004338:Drug Combinations; D009292:Narcotic Antagonists; C503788:Oxytrex; D009271:Naltrexone; D010098:Oxycodone