Ahmedzai, S.H., Nauck, F., Bar-Sela, G., Bosse, B., Leyendecker, P., & Hopp, M. (2012). A randomized, double-blind, active-controlled, double-dummy, parallel-group study to determine the safety and efficacy of oxycodone/naloxone prolonged-release tablets in patients with moderate/severe, chronic cancer pain. Palliative Medicine, 26, 50-60.

To determine whether oxycodone/naloxone prolonged-release tablets (OXN PR), as compared with oxycodone prolonged-release tablets (OxyPR), can improve constipation and maintain analgesia in patients with moderate or severe chronic cancer pain.  

Stopping their prestudy opioid and laxative medication, eligible patients were randomized to receive one of two treatments, OXN PR or OxyPR, for a four-week double-blind treatment phase. After beginning the study, patients attended three additional clinic visits, once weekly. Oxycodone immediate-release capsules were available as pain rescue medication and bisacodyl tablets were available as laxative rescue medication. Evaluations of bowel function, pain control, use of rescue medication, and use of laxative medication during the prior seven days were performed at each clinic visit. Quality-of-life (QOL) assessments were conducted at screening and study end.

• In this sample, 133 of 184 patients (72.3%) completed the study.
• Patients were aged 18 years or older. Mean patient age was 61.86 years (SD = 10.93, median = 62, range 36-84) in the OXN PR group and 64.3 years (SD = 9.63, median = 66, range 42-82) in the OxyPR group. 
• The OXN PR group was 52% male and 48% female, whereas the OxyPR group was 50% male and 50% female.
• Key disease characteristics were having a diagnosis of cancer and moderate or severe, chronic pain requiring around-the-clock opioid therapy, with constipation induced or worsened by the opioid medication.
• Patients were excluded if they had clinically unstable disease; significant cardiovascular, renal, hepatic, or psychiatric disease; clinically significant gastrointestinal (GI) disease; significant structural abnormality of the GI tract; cyclic chemotherapy within two weeks before the screening visit; planned chemotherapy during the study; or radiotherapy that would influence bowel function or pain.

• Multi-site
• Outpatient
• International  (64 study sites in Australia, Czech Republic, France, Germany, Hungary, Israel, Netherlands, Poland, and United Kingdom)

Patients were undergoing the active treatment phase of care.

This was a randomized, double-blind, active-controlled, double-dummy, parallel-group, phase II trial.

• Bowel Function Index (BFI)
• Brief Pain Inventory (Short Form) (BPI-SF)
• EuroQol EQ-5D
• European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30)
• Patient Assessment of Constipation Symptoms (PAC-SYM)
• Modified Subjective Opiate Withdrawal Scale (SOWS)
   

• Mean BFI score was significantly lower in the OXN PR group (p ˂ 0.01) after four weeks of treatment.
• Mean total laxative intake was 20% lower in the OXN PR group, but the difference was not statistically significant (p = 0.17).
• Mean BPI-SF scores and analgesic rescue medication use were similar for both groups.
• The OXN PR group had greater improvements in constipation-specific QOL assessments in terms of total symptom score (p = 0.014) and frequency of symptoms (p ˂ 0.01).
• Adverse events were similar and low in both groups.

OXN PR, as compared with OxyPR, seems to provide comparable analgesia for patients with moderate or severe cancer pain while significantly improving bowel function and reducing symptoms of constipation.

Demographic characteristics were generally well balanced between treatment groups, with the exception of a slightly higher percentage of patients aged 65 years or younger in the OXN PR group. 

OXN PR seems superior to OxyPR with respect to bowel function by reducing constipation without compromising pain relief. In addition, patients receiving OXN PR had improved QOL with decreased opioid-induced constipation complications.