(799): Oxytrex has minimal physical dependence and improved safety vs. oxycodone in phase III clinical trial in low-back pain

Abstract

Opioid drugs have a legitimate medical use as powerful pain relievers but also cause undesired side-effects. Physical dependence is characterized by a set of intense clinical (withdrawal) symptoms that appear when prolonged opioid use is terminated. Oxytrex™ (oxycodone+ ultra-low-dose naltrexone) is a new oral investigational drug shown here to provide strong analgesia in a twice-daily dosing regimen while minimizing physical dependence. In this 719-patient, double-blind, placebo- and active-controlled Phase III clinical trial in chronic moderate-to-severe low-back pain, patients were randomized to receive placebo, oxycodone QID, or Oxytrex QID or BID. Each Oxytrex tablet contains 1 microgram of naltrexone formulated with the oxycodone; Oxytrex BID and QID treatments provided 2 and 4 micrograms naltrexone/day, respectively. Following a washout, patients with low-back pain ≥ 5 on a 0-10 scale were dose-escalated every week using 10 to 80 mg of daily drug (or matching placebo) until they attained adequate pain relief (≤ 2) or until they reported just bearable side-effects, at which point patients were fixed on that steady dose for 12 weeks. All patients in drug groups attained equal analgesia during the 12-week study, despite significantly lower drug use (p= 0.03) by Oxytrex patients. Patients on Oxytrex BID also reported 44% less moderate-to-severe constipation (p= 0.01), 33% less moderate-to-severe somnolence (p= 0.03), and 51% less moderate-to-severe pruritis (p< 0.001). Drug treatment ceased at the conclusion of the study, and patients were evaluated for opioid dependence and withdrawal symptoms using the Short Opioid Withdrawal Scale (SOWS). Patients taking Oxytrex BID reported dramatically less (55%) physical dependence (p= 0.01) compared to patients on oxycodone in the 24 hours following cessation of opioid use. This is the first large, well-controlled study to show strong pain relief with minimal withdrawal symptoms and better safety compared to oxycodone. Opioid drugs have a legitimate medical use as powerful pain relievers but also cause undesired side-effects. Physical dependence is characterized by a set of intense clinical (withdrawal) symptoms that appear when prolonged opioid use is terminated. Oxytrex™ (oxycodone+ ultra-low-dose naltrexone) is a new oral investigational drug shown here to provide strong analgesia in a twice-daily dosing regimen while minimizing physical dependence. In this 719-patient, double-blind, placebo- and active-controlled Phase III clinical trial in chronic moderate-to-severe low-back pain, patients were randomized to receive placebo, oxycodone QID, or Oxytrex QID or BID. Each Oxytrex tablet contains 1 microgram of naltrexone formulated with the oxycodone; Oxytrex BID and QID treatments provided 2 and 4 micrograms naltrexone/day, respectively. Following a washout, patients with low-back pain ≥ 5 on a 0-10 scale were dose-escalated every week using 10 to 80 mg of daily drug (or matching placebo) until they attained adequate pain relief (≤ 2) or until they reported just bearable side-effects, at which point patients were fixed on that steady dose for 12 weeks. All patients in drug groups attained equal analgesia during the 12-week study, despite significantly lower drug use (p= 0.03) by Oxytrex patients. Patients on Oxytrex BID also reported 44% less moderate-to-severe constipation (p= 0.01), 33% less moderate-to-severe somnolence (p= 0.03), and 51% less moderate-to-severe pruritis (p< 0.001). Drug treatment ceased at the conclusion of the study, and patients were evaluated for opioid dependence and withdrawal symptoms using the Short Opioid Withdrawal Scale (SOWS). Patients taking Oxytrex BID reported dramatically less (55%) physical dependence (p= 0.01) compared to patients on oxycodone in the 24 hours following cessation of opioid use. This is the first large, well-controlled study to show strong pain relief with minimal withdrawal symptoms and better safety compared to oxycodone.