Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain.
This randomized, double-blind, placebo- and active-controlled, parallel-group study was designed to demonstrate the superiority of oxycodone in combination with naloxone in a prolonged release (PR) formulation over placebo with respect to analgesic efficacy. The active control group was included for sensitivity and safety analyses, and furthermore to compare the analgesic efficacy and bowel function of oxycodone PR/naloxone PR with oxycodone PR alone. The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events (ie, inadequate analgesia) in patients with moderate to severe chronic low back pain. The full analysis population consisted of 463 patients. The times to recurrent pain events were significantly longer in the oxycodone PR/naloxone PR group compared with placebo (P < .0001-.0003); oxycodone PR/naloxone PR reduced the risk of pain events by 42% (P < .0001; full analysis population). The appearance of pain events was comparable for oxycodone PR/naloxone PR versus oxycodone PR, confirming that the addition of naloxone PR to oxycodone PR in a combination tablet did not negatively affect analgesic efficacy of the opioid. Furthermore, oxycodone PR/naloxone PR offers benefits in terms of an improvement in bowel function. In a therapeutic area of great unmet need, therefore, the combination tablet of oxycodone PR/naloxone PR offers patients effective analgesia while improving opioid-induced bowel dysfunction. Taken together with the observation that the safety profile of oxycodone PR/naloxone PR is consistent with that expected from other opioid analgesics except opioid-induced constipation, these findings indicate that the addition of naloxone to oxycodone in a PR combination tablet offers improved tolerability. Oxycodone PR/naloxone PR is therefore a promising new treatment approach for the management of chronic pain.


CONCLUSIONS
This study evaluated the analgesic efficacy and safety of the combination of oxycodone PR/naloxone PR in chronic nonmalignant pain. Opioids are often reduced in dosage or even discontinued as a result of impaired bowel function, leading to insufficient pain treatment. Not only does oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with oxycodone PR, but it also improves opioid-induced bowel dysfunction, and may therefore improve the acceptability of long-term opioid treatment for chronic pain.
Vondrackova
Dana
D
CLB FN Bulovka, Praha, Czech Republic.
Leyendecker
Petra
P
Meissner
Winfried
W
Hopp
Michael
M
Szombati
Istvan
I
Hermanns
Kai
K
Ruckes
Christian
C
Weber
Susanne
S
Grothe
Birgit
B
Fleischer
Wolfgang
W
Reimer
Karen
K
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002908:Chronic Disease; D003248:Constipation / Q000139:chemically induced; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010147:Pain Measurement / Q000379:methods; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009270:Naloxone; D010098:Oxycodone