Prolonged-Release (PR) Oxycodone/Naloxone Improves Bowel Function Compared with Oxycodone PR and Provides Effective Analgesia in Chinese Patients with Non-malignant Pain: A Randomized, Double-Blind Trial

Abstract

Introduction: Prolonged-release oxycodone/naloxone (OXN PR), combining an opioid analgesic with selective blockade of enteric µ-opioid receptors, provided effective analgesia and improved bowel function in patients with moderate-to-severe pain and opioid-induced constipation in clinical trials predominantly conducted in Western countries. This double-blind randomized controlled trial investigated OXN PR (N = 116) versus prolonged-release oxycodone (OXY PR, N = 115) for 8 weeks at doses up to 50 mg/day in patients with moderate-to-severe, chronic, non-malignant musculoskeletal pain and opioid-induced constipation recruited in China.

Methods: A total of 234 patients at least 18 years of age with non-malignant musculoskeletal pain for more than 4 weeks that was moderate-to-severe in intensity and required round-the-clock opioid therapy were randomized (1:1) to OXN PR or OXY PR. The primary endpoint was bowel function using the Bowel Function Index (BFI). Secondary endpoints included safety, Brief Pain Inventory-Short Form (BPI-SF), use of analgesic and laxative rescue medication, and health-related quality of life (EQ-5D).

Results: While BFI scores were comparable at baseline, at week 8 improvements were greater with OXN PR vs OXY PR (least squares mean [LSM] difference (95% CI) - 9.1 (- 14.0, - 4.2); P < 0.001. From weeks 2 to 8, mean BFI scores were in the range of normal bowel function (≤ 28.8) with OXN PR but were in the range of constipation (> 28.8) at all timepoints with OXY PR. Analgesia with OXN PR was similar and non-inferior to OXY PR on the basis of modified BPI-SF average 24-h pain scores at week 8: LSM difference (95% CI) - 0.3 (- 0.5, - 0.1); P < 0.001. The most frequent treatment-related AEs were nausea (OXN PR 5% vs OXY PR 6%) and dizziness (4% vs 4%).

Conclusion: OXN PR provided clinically meaningful improvements in bowel function and effective analgesia in Chinese patients with moderate-to-severe musculoskeletal pain and pre-existing opioid-induced constipation.

Trial registration: ClinicalTrials.gov, identifier NCT01918098.

Keywords: Bowel function index; China; Musculoskeletal pain; Opioid-induced constipation; Pain; Prolonged-release oxycodone/naloxone.

Fig. 1

Patient disposition. OXN PR prolonged-release oxycodone/naloxone, OXY PR prolonged-release oxycodone. Full analysis population comprised patients who received at least one dose of study medication and had at least one assessment during double-blind treatment; per protocol population comprised patients who received at least one dose of study medication and complied with the study protocol; safety population comprised patients who received at least one dose of double-blind study medication. *n = 138 due to not meeting constipation criteria and n = 3 due to inadequate analgesia with OXY PR 50 mg/day

Fig. 2

Bowel Function Index Scores at each study visit (full analysis population). BFI Bowel Function Index, EOT end of study treatment, OXN PR prolonged-release oxycodone/naloxone, OXY PR prolonged-release oxycodone. Data are mean ± SD. Lower scores indicate better bowel function. *P ≤ 0.01 (two-sided t test). EOT data could be included from patients without data at all study timepoints. Hashed line represents the BFI threshold of 28.8 for normal bowel function in patients with pain (higher scores indicated worse constipation symptoms) [29]

Fig. 3

Modified BPI-SF: average pain over the last 24 h (per protocol population). BPI-SF Brief Pain Inventory-Short Form, EOT end of study treatment, OXN PR prolonged-release oxycodone/naloxone, OXY PR prolonged-release oxycodone. Data are mean ± SD. Lower scores indicate less pain. *P ≤ 0.01 (two-sided t test) for non-inferiority with a margin of 0.8. BPI-SF scale: 0 = no pain to 10 = pain as bad as you can imagine. EOT data could be included from patients without data at all study timepoints