Blagden, M., Hafer, J., Duerr, H., Hopp, M., & Bosse, B. (2014). Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: Pooled analysis of extension phases of two phase III trials. Neurogastroenterology and Motility, 26, 1792–1801. 

To evaluate the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain.

474 patients received open-labeled OXN PR during 52 weeks of extension phases of two studies, having completed 12 weeks of double-blinded, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) (n = 160) or OXN PR (n = 162). The starting dose was the effective analgesic dose of OXY or OXN that the patient received at the end of the double-blind phase. Dose titration was to a maximum of 80 mg per day (OXN3001S) or 120 mg per day (OXN3006S) at the discretion of the investigator. Use of laxatives and analgesic rescue therapy was recorded in patient diaries. Oxycodone immediate-release (IR) and bisacodyl were provided for the first seven days of the extension phase. Protocols for rescue medicines and laxatives were prescribed according to standard protocols of the investigational sites. There were seven mandated office visits.

• N = 474  
• AGE = 362 aded 65 and younger; 112 older than age 65
• MALES: 36.9%, FEMALES: 63.1%

• SITE: Multi-site    
• SETTING TYPE: Not specified

• PHASE OF CARE: Mutliple phases of care

• Pooled analysis of two Phase III double-blind, randomized studies

• Analgesia and bowel function were assessed at each study visit using average pain over last 24 hours scale and Bowel Function Index (BFI).
• Treatment Satisfaction Questionnaire for Medication (TSQM) was assessed at end of study only.

Improvement in bowel function was seen when patients switched from Oxy PR in the double-blinded phase to OXN PR in the extension phase, resulting in a clinical reduction (greater points) in BFI score: At the start of the extension phases, mean BFI score was 44.3 (SD = 28.13) and was 29.8 (SD = 2.36) for patients who had received OXN PR in the double-blinded phase. One week later, BFI scores were similar for the two groups (26.5 [SD = 24.4] and 27.5 [SD = 25.6], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-hour pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed.

Pooled data demonstrated OXN PR in patients with moderate-to-severe chronic pain is an effective long-term therapy for patient opioid-induced pain. Improvement in bowel function was seen during the double-blinded studies and was continued throughout the 52 weeks of OXN PR versus Oxy PR in this pooled analysis. No new or unexpected safety issues were observed, and patient satisfaction was high and maintained throughout the 52 weeks.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Prolonged-release oxycodone/naloxone (OXN PR) is a good option for patients with opioid-induced constipation.