Number of included patients:
J Pain. 2006 Dec;7(12):937-46.
Oxytrex minimizes physical dependence while providing effective analgesia: a randomized controlled trial in low back pain.
Webster LR, Butera PG, Moran LV, Wu N, Burns LH, Friedmann N.
Lifetree Clinical Research, Salt Lake City, Utah, USA.
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. PERSPECTIVE: 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.