Oxytrex minimizes physical dependence while providing effective analgesia: a randomized controlled trial in low back pain.
Physical dependence or withdrawal is an expected effect of prolonged opioid therapy. Oxytrex (oxycodone + ultralow-dose naltrexone) is an investigational drug shown here to minimize physical dependence while providing strong analgesia with twice-daily dosing. In this 719-patient, double-blind, placebo- and active-controlled Phase III clinical trial in chronic low back pain, patients were randomized to receive placebo, oxycodone qid, or oxytrex qid or bid. Each oxytrex tablet contains 1 microg naltrexone; oxytrex bid and qid treatments provide 2 and 4 microg naltrexone/day, respectively. Following a washout, patients with pain >or=5 on a 0-10 scale were dose-escalated weekly from 10 up to 80 mg/day until reaching adequate pain relief (<or=2) or a tolerable level of side effects. Following titration, the dose was fixed for 12 weeks. Active treatment groups attained comparable analgesia despite significantly lower drug use (P = .03) by oxytrex patients. Patients taking oxytrex bid reported 55% less physical dependence than patients on oxycodone (P = .01) by the Short Opiate Withdrawal Scale 24 h after treatment cessation. Oxytrex bid patients also reported decreased moderate-to-severe constipation (by 44%, P = .01), somnolence (by 33%, P = .03), and pruritus (by 51%, P < .001). This is the first large well controlled study to show strong analgesia with minimal withdrawal symptoms and better safety compared with oxycodone.


CONCLUSIONS
Previous clinical data have shown ultralow-dose naltrexone enhances and prolongs oxycodone analgesia, and preclinical data also show a suppression of opioid tolerance and dependence. A cellular mechanism of action has been demonstrated to be the prevention of aberrant G protein signaling by mu opioid receptors caused by chronic opioid administration.
Webster
Lynn R
LR
Lifetree Clinical Research, Salt Lake City, Utah, USA.
Butera
Peter G
PG
Moran
Lauren V
LV
Wu
Nancy
N
Burns
Lindsay H
LH
Friedmann
Nadav
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000627:therapeutic use*; D010098:Oxycodone / Q000627:therapeutic use*; D010147:Pain Measurement / Q000379:methods; D013375:Substance Withdrawal Syndrome; D016896:Treatment Outcome
D000700:Analgesics; C503788:Oxytrex; D009271:Naltrexone; D010098:Oxycodone