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

• Published in: Advances in therapy Vol. 37; no. 3; pp. 1188 - 1202
• Main Authors: Leng, Xiaomei, Zhang, Fengxiao, Yao, Shanglong, Weng, Xisheng, Lu, Kaizhi, Chen, Gouzhong, Huang, Ming, Huang, Yuguang, Zeng, Xiaofeng, Hopp, Michael, Lu, Guodong
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.03.2020
• Subjects: Aged; Aged, 80 and over; Analgesics - administration & dosage; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - therapeutic use; Cardiology; China; Chronic Pain - drug therapy; Delayed-Action Preparations - administration & dosage; Double-Blind Method; Drug Combinations; Endocrinology; Female; Humans; Internal Medicine; Laxatives - administration & dosage; Male; Medicine; Medicine & Public Health; Middle Aged; Naloxone - administration & dosage; Naloxone - adverse effects; Naloxone - therapeutic use; Oncology; Opioid-Induced Constipation - prevention & control; Original Research; Oxycodone - administration & dosage; Oxycodone - adverse effects; Oxycodone - therapeutic use; Pain Management - adverse effects; Pain Management - methods; Pharmacology/Toxicology; Quality of Life; Rheumatology; China; Opioid-induced constipation; Musculoskeletal pain; Bowel function index; Pain; Prolonged-release oxycodone/naloxone; China
• ISSN: 0741-238X; 1865-8652
• DOI: 10.1007/s12325-020-01244-x

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.