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

Overview

Journal Adv Ther

Date 2020 Feb 6

PMID 32020565

Citations 2

Authors

Xiaomei Leng

Fengxiao Zhang

Shanglong Yao

Xisheng Weng

Kaizhi Lu

Gouzhong Chen

Ming Huang

Yuguang Huang

Xiaofeng Zeng

Michael Hopp

Guodong Lu

Affiliations

Soon will be listed here.

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.

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References

Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D . Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2005; 10(4):287-333. DOI: 10.1016/j.ejpain.2005.06.009. View

Chen B, Li L, Donovan C, Gao Y, Ali G, Jiang Y . Prevalence and characteristics of chronic body pain in China: a national study. Springerplus. 2016; 5(1):938. PMC: 4929094. DOI: 10.1186/s40064-016-2581-y. View

Jackson T, Chen H, Iezzi T, Yee M, Chen F . Prevalence and correlates of chronic pain in a random population study of adults in Chongqing, China. Clin J Pain. 2013; 30(4):346-52. DOI: 10.1097/AJP.0b013e31829ea1e3. View

Johannes C, Le T, Zhou X, Johnston J, Dworkin R . The prevalence of chronic pain in United States adults: results of an Internet-based survey. J Pain. 2010; 11(11):1230-9. DOI: 10.1016/j.jpain.2010.07.002. View

Reid K, Harker J, Bala M, Truyers C, Kellen E, Bekkering G . Epidemiology of chronic non-cancer pain in Europe: narrative review of prevalence, pain treatments and pain impact. Curr Med Res Opin. 2011; 27(2):449-62. DOI: 10.1185/03007995.2010.545813. View

Wong W, Fielding R . Prevalence and characteristics of chronic pain in the general population of Hong Kong. J Pain. 2010; 12(2):236-45. DOI: 10.1016/j.jpain.2010.07.004. View

De Sola H, Salazar A, Duenas M, Ojeda B, Failde I . Nationwide cross-sectional study of the impact of chronic pain on an individual's employment: relationship with the family and the social support. BMJ Open. 2016; 6(12):e012246. PMC: 5223634. DOI: 10.1136/bmjopen-2016-012246. View

Epstein R, Teagarden J, Cimen A, Sostek M, Salimi T . When People with Opioid-Induced Constipation Speak: A Patient Survey. Adv Ther. 2017; 34(3):725-731. PMC: 5350191. DOI: 10.1007/s12325-017-0480-4. View

Gannon B, Finn D, OGorman D, Ruane N, McGuire B . The cost of chronic pain: an analysis of a regional pain management service in Ireland. Pain Med. 2013; 14(10):1518-28. DOI: 10.1111/pme.12202. View

10.

Gaskin D, Richard P . The economic costs of pain in the United States. J Pain. 2012; 13(8):715-24. DOI: 10.1016/j.jpain.2012.03.009. View

11.

Chou R, Fanciullo G, Fine P, Adler J, Ballantyne J, Davies P . Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 10(2):113-30. PMC: 4043401. DOI: 10.1016/j.jpain.2008.10.008. View

12.

OBrien T, Christrup L, Drewes A, Fallon M, Kress H, McQuay H . European Pain Federation position paper on appropriate opioid use in chronic pain management. Eur J Pain. 2016; 21(1):3-19. PMC: 6680203. DOI: 10.1002/ejp.970. View

13.

Dowell D, Haegerich T, Chou R . CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016. JAMA. 2016; 315(15):1624-45. PMC: 6390846. DOI: 10.1001/jama.2016.1464. View

14.

Xia Z . Cancer pain management in China: current status and practice implications based on the ACHEON survey. J Pain Res. 2017; 10:1943-1952. PMC: 5571848. DOI: 10.2147/JPR.S128533. View

15.

Manchikanti L, Kaye A, Knezevic N, McAnally H, Slavin K, Trescot A . Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines. Pain Physician. 2017; 20(2S):S3-S92. View

16.

Holzer P . Opioid receptors in the gastrointestinal tract. Regul Pept. 2009; 155(1-3):11-7. PMC: 3163293. DOI: 10.1016/j.regpep.2009.03.012. View

17.

Sobczak M, Salaga M, Storr M, Fichna J . Physiology, signaling, and pharmacology of opioid receptors and their ligands in the gastrointestinal tract: current concepts and future perspectives. J Gastroenterol. 2013; 49(1):24-45. PMC: 3895212. DOI: 10.1007/s00535-013-0753-x. View

18.

Bell T, Panchal S, Miaskowski C, Bolge S, Milanova T, Williamson R . The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med. 2008; 10(1):35-42. DOI: 10.1111/j.1526-4637.2008.00495.x. View

19.

COOK S, Lanza L, Zhou X, Sweeney C, Goss D, Hollis K . Gastrointestinal side effects in chronic opioid users: results from a population-based survey. Aliment Pharmacol Ther. 2008; 27(12):1224-32. DOI: 10.1111/j.1365-2036.2008.03689.x. View

20.

LoCasale R, Datto C, Margolis M, Coyne K . Satisfaction with Therapy Among Patients with Chronic Noncancer Pain with Opioid-Induced Constipation. J Manag Care Spec Pharm. 2016; 22(3):246-53. PMC: 10397723. DOI: 10.18553/jmcp.2016.22.3.246. View