Abstract
Introduction
Two randomized, double-blind, placebo-controlled studies in acute and chronic pain treatment, powered to assess noninferiority of the efficacy of tapentadol immediate release (IR) (50 mg, 75 mg) versus oxycodone hydrochloride (HCl) IR (10 mg), established comparable efficacy of tapentadol IR with oxycodone HCl IR, and suggested tapentadol IR’s improved gastrointestinal tolerability. The impact of these equianalgesic doses of tapentadol and oxycodone HCl on bowel function and gastrointestinal tolerability was then directly assessed in the current study, using a validated bowel function diary to comprehensively assess opioid-induced constipation symptoms and outcomes.
Methods
In this double-blind study, patients with end-stage joint disease were randomized to tapentadol IR (50 mg or 75 mg), oxycodone HCl IR 10 mg, or placebo. Treatment with IR formulations (14 days) was followed by treatment (28 days) with extended-release (ER) formulations of active drugs (or placebo).
Results
Oxycodone HCl IR treatment significantly decreased (P<0.001) mean (SD) number of spontaneous bowel movements over the 14-day period (average per week: [6.7 (5.44)] versus tapentadol IR 50 mg [9.0 (4.04)], tapentadol IR 75 mg [8.6 (4.65)], and placebo [9.9 (5.16)]) (primary measure), confirming the tolerability findings of the earlier studies. Additionally, incidences of nausea and vomiting were significantly lower over the 14-day period (nominal P<0.001) for tapentadol IR 50 and 75 mg, versus oxycodone HCl IR 10 mg. Results with ER formulations of tapentadol and oxycodone HCl over a longer treatment period were consistent with those of IR formulations.
Conclusion
Tapentadol IR (50 mg, 75 mg) consistently demonstrated superior gastrointestinal tolerability, including for the most commonly reported events, such as nausea, vomiting, and constipation at doses that provide comparable efficacy with oxycodone HCl IR 10 mg. These findings validate and extend the tolerability findings of the two earlier studies that established comparable efficacy of these tapentadol and oxycodone HCl doses.
Similar content being viewed by others
References
Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain. 2002;3:159–180.
Moore RA, McQuay HJ. Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids. Arthritis Res Ther. 2005;7:R1046–R1051.
Avouac J, Gossec L, Dougados M. Efficacy and safety of opioids for osteoarthritis: a meta-analysis of randomized controlled trials. Osteoarthritis Cartilage. 2007;15:957–965.
Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001;182(Suppl 5A):11S–18S.
Thorpe DM. Management of opioid-induced constipation. Curr Pain Headache Rep. 2001;5:237–240.
Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112:372–380.
Tzschentke TM, Christoph T, Kogel B, et al. (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther. 2007;323:265–276.
Tzschentke TM, De Vry J, Terlinden R, et al. Tapentadol hydrochloride. Drugs Future. 2006;31:1053–1061.
NUCYNTA (tapentadol) [product information]. Titusville, NJ, USA: Ortho-McNeil-Janssen Pharmaceuticals Inc.; 2010. Available at: www.nucynta.com/nucynta/assets/Nucynta-PI.pdf. Accessed May 22, 2010.
Terlinden R, Kogel BY, Englberger W, Tzschentke TM. In vitro and in vivo characterization of tapentadol metabolites. Methods Find Exp Clin Pharmacol. 2010;32:31–38.
Daniels S, Casson E, Stegmann JU, et al. A randomized, double-blind, placebo-controlled phase 3 study of the relative efficacy and tolerability of tapentadol IR and oxycodone IR for acute pain. Curr Med Res Opin. 2009;25:1551–1561.
Hartrick C, Van Hove I, Stegmann JU, Oh C, Upmalis D. Efficacy and tolerability of tapentadol immediate release and oxycodone HCl immediate release in patients awaiting primary joint replacement surgery for end-stage joint disease: a 10-day, phase III, randomized, double-blind, active- and placebo-controlled study. Clin Ther. 2009;31:260–271.
Clinicaltrials.gov, NCT00361582. A randomized, double-blind, active- and placebo-controlled, parallel group, multicenter study to evaluate the efficacy and safety of multiple doses of CG5503 immediate release formulation in subjects awaiting primary joint replacement surgery for end-stage joint disease; NCT00361582. Available at: http://download.veritasmedicine.com/PDF/CR011218_CSR.pdf. 2010. Accessed April 26, 2010.
FDA.gov. U.S. Department of Health and Human Services/Food and Drug Administration. Guidance for industry patient-reported outcome measures: use in medical product development to support labeling claims. Available at: www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM193282.pdf. Accessed June 1, 2010.
Camilleri M, Rothman M, Ho KF, Etropolski M. Validation of a bowel function diary for assessing opioid-induced constipation. Am J Gastroenterol. 2010;106:497–506.
World Health Organization. WHO’s pain relief ladder. 2010; Available at: www.who.int/cancer/palliative/painladder/en/. Accessed May 25, 2010.
O’Donnell LJ, Virjee J, Heaton KW. Detection of pseudodiarrhoea by simple clinical assessment of intestinal transit rate. BMJ. 1990;300:439–440.
Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003;35:253–259.
Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491.
Bonferroni CE. Il calcolo delle assicurazioni su gruppi di teste. In: Carboni, SO, eds. Studi in Onore del Professore Salvatore Ortu Carboni. Rome, Italy; 1935:13–60.
Camilleri M. Opioid-induced constipation: challenges and therapeutic opportunities. Am J Gastroenterol. 2011; Feb 22 [Epub ahead of print].
FDA.gov. U.S. Department of Health and Human Services/Food and Drug Administration. Guidance for Industry. Irritable Bowel Syndrome — Clinical evaluation of products for treatment. Available at: http://www.fda.gov/downloads/Drugs/GuidanceCom-plianceRegulatoryInformation/Guidances/UCM205269.pdf. Accessed February 27, 2011.
Kavanagh S, Kwong W, Hammond G, et al. Bowel function following tapentadol and oxycodone immediate release (IR) treatment in subjects with end stage joint disease: post-hoc analysis of data from a randomized, double-blind, active- and placebo-controlled study. J Pain. 2009;10(Supp. 1):S43.
Stegmann JU, Weber H, Steup A, Okamoto A, Upmalis D, Daniels S. The efficacy and tolerability of multiple-dose tapentadol immediate release for the relief of acute pain following orthopedic (bunionectomy) surgery. Curr Med Res Opin. 2008;24:3185–3196.
Hale M, Upmalis D, Okamoto A, Lange C, Rauschkolb C. Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized, double-blind study. Curr Med Res Opin. 2009;25:1095–1104.
Daniels SE, Upmalis D, Okamoto A, Lange C, Haeussler J. A randomized, double-blind, phase III study comparing multiple doses of tapentadol IR, oxycodone IR, and placebo for postoperative (bunionectomy) pain. Curr Med Res Opin. 2009;25:765–776.
Etropolski MS, Okamoto A, Shapiro DY, Rauschkolb C. Dose conversion between tapentadol immediate and extended release for low back pain. Pain Physician. 2010;13:61–70.
Afilalo M, Etropolski M, Kuperwasser B, et al. Efficacy and safety of tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: results of a randomized, double-blind, placebo- and activecontrolled phase 3 study. Clin Drug Investig. 2010;30:489–505.
Buynak R, Shapiro DY, Okamoto A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled phase III study. Expert Opin Pharmacother. 2010;11:1787–1804.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Etropolski, M., Kelly, K., Okamoto, A. et al. Comparable efficacy and superior gastrointestinal tolerability (nausea, vomiting, constipation) of tapentadol compared with oxycodone hydrochloride. Adv Therapy 28, 401–417 (2011). https://doi.org/10.1007/s12325-011-0018-0
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12325-011-0018-0