New Data Show Prolonged Release Oxycodone/Naloxone Provides Effective Pain Relief and Reduces OIC in Patients with Severe Chronic Pain
Results of Phase II and III trials add to growing bank of clinical evidence regarding prolonged release oxycodone / naloxone
Cambridge, UK, August 19, 2008- Prolonged release oxycodone / naloxone is as effective as oxycodone alone in providing pain relief for patients with moderate to severe chronic pain while reducing the risk of opioid-induced constipation (OIC), according to new phase II and III data presented today at the 12th World Congress on Pain in Glasgow, Scotland.
Phase II and III clinical data from three multinational, randomised double-blind studies involving more than 1,000 patients demonstrate that the prolonged release oxycodone / naloxone combination is an effective opioid analgesic, providing equivalent pain relief to oxycodone alone in patients with severe chronic pain.1
These studies1 measured the analgesic efficacy of prolonged release oxycodone / naloxone using pain scale values measuring average daily pain. The extension phase of the study demonstrated that 24 hour average pain values using the oxycodone / naloxone prolonged release combination are comparable to prolonged release oxycodone, and remained low and stable over 12 months.1,3
In a second Phase III study, prolonged release oxycodone / naloxone was also shown to improve bowel function when compared to prolonged release oxycodone.2 The study measured bowel movement, frequency of laxative intake and stool consistency. Results confirm that the prolonged release oxycodone / naloxone combination reduces OIC, with an improvement in bowel function as early as one week in some patients.
Patient benefits of opioid analgesia with a reduced risk of OIC is demonstrated in a third study recently published in the International Journal of Clinical Practice, showing that patients prefer prolonged release oxycodone in combination with naloxone to prolonged release oxycodone alone.4 The study also indicates that increased naloxone doses of 10mg, 20mg or 40mg/day are associated with improved patient assessment of their pain relief therapy.
"Management of severe pain with strong opioids is unfortunately associated with a number of side effects. The most prevalent side effect is development of constipation. Constipation may lead to discomfort and ineffective analgesia." says Dr Mads Werner, MD, DMSc of the Multidisciplinary Pain Center, Rigshospitalet, Copenhagen, Denmark. "The new generation of prokinetic drugs, with peripheral opioid antagonistic actions, seems to offer our patients a more effective solution to opioid-induced bowel problems than conventional laxative therapies."
Prolonged release oxycodone / naloxone tablets are a pain relief medication and belong to the class of analgesics known as opioids, which include codeine and morphine. Although highly effective in the control of pain, the use of opioids is associated with opioid-induced constipation (OIC), a potentially debilitating side-effect which can affect up to 95 percent of patients who are treated with these medications.5
Constipation can be defined as a decrease in the passage of formed stools and characterised by stools that are hard and difficult to pass.6 OIC is often accompanied by other gastrointestinal side effects such as decreased gastric emptying, abdominal cramping and bloating. It is also associated with nausea, vomiting and gastro-oesophageal reflux (where acid from the stomach leaks up into the oesophagus).7,8
The prolonged release tablet contains two active ingredients — oxycodone, a strong opioid which treats pain, and naloxone, a compound which reduces the constipation caused by the opioid.1,2 Prolonged release oxycodone / naloxone tablets provide effective pain relief with reduced constipation, through the combination of oxycodone, which is able to reach the central opioid receptors in the brain and block the perception of pain. At the same time, naloxone prevents the opioid from reaching the peripheral receptors in the gut.1,2
A fourth study shows that treatment with 5/2.5mg prolonged release oxycodone / naloxone tablets is bioequivalent to oxycodone 5mg, and supports earlier studies with higher strength tablets with respect to key pharmacokinetic properties.9
Notes to editors About prolonged release oxycodone / naloxone Oxycodone / naloxone is marketed in Germany under the brand name Targin® and is a combination of the strong opioid analgesic oxycodone and the opioid receptor antagonist naloxone in prolonged release formulation. It is currently licensed for use in Germany only.
Oxycodone is a strong opioid analgesic, used for the treatment of severe chronic pain. Its efficacy has been demonstrated across a broad spectrum of severe pain states such as somatic and neuropathic pain.10,11 Recent experimental data in volunteers also suggest that oxycodone may be useful for the treatment of severe visceral pain.12,13
Naloxone is an opioid receptor antagonist that, when taken orally, has negligible systemic bioavailability, providing a full inhibitory effect on local opioid receptors in the gut – reducing opioid-induced constipation – without impacting on the centrally acting analgesic efficacy of oxycodone.
Prolonged release oxycodone / naloxone has been clinically proven to provide comparable analgesic efficacy to that of oxycodone, whilst significantly reducing OIC, a class effect associated with all opioids. Prolonged release oxycodone / naloxone is a prolonged-release formulation providing twice-daily dosing.
*Targin® is a registered trademark.
About Mundipharma International Ltd. The Mundipharma independent associated companies, including Mundipharma, Purdue and Napp, are privately owned companies and joint ventures covering the world's pharmaceutical markets. The companies worldwide are dedicated to bringing to patients with severe and debilitating diseases the benefits of novel treatment options in fields such as severe pain, haemato-oncology and respiratory disease. Prolonged release oxycodone / naloxone was developed by Mundipharma Research. For more information: www.mundipharma.co.uk<http://www.mundipharma.co.uk/>
Contacts Aoife Gallagher Tel: +44 (0) 7981 429 797 Fax: +44 (0) 20 7331 9084 Email: aoife.gallagher@cohnwolfe.com
Emily Bunting Tel: +44 (0) 20 7331 5310 Fax: +44 (0) 20 7331 9084 Email: emily.bunting@cohnwolfe.com Date of Preparation August 2008 – UK/TAR-08047
References 1. Simpson K, Meissner W, Leyendecker P. Analgesic efficacy of oxycodone in combination with naloxone as prolonged release (PR) tablets in patients with moderate to severe chronic pain [abstract]. Proceedings of the 12th World Congress on Pain; 2008 Aug 17-22; Glasgow, UK 2. Müller-Lissner S, Löwenstein O, Leyendecker P. Improved bowel function with a combination of oxycodone and naloxone (OXN) as prolonged release (PR) tablets in patients with moderate to severe chronic pain [abstract]. Proceedings of the 12th World Congress on Pain; 2008 Aug 17-22; Glasgow, UK 3. Meissner W, Hopp M, Leyendecker P. et al. Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain [abstract]. Proceedings of the 41st Annual Scientific Meeting of the British Pain Society; 2008 Apr 15-18; Liverpool, UK 4. Nadstawek J, Leyendecker P, Hopp M, et al. Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain. Int J Clin Prac 2008;62(8):1159-1167 5. Robinson CB, Fritch M, Hullett L, et al. Development of a protocol to prevent opioid-induced constipation in patients with cancer: a research utilization project. Clin J Oncol Nurs 2000;14(2):79-84 6. McMillan SC. Assessing and managing opiate-induced constipation in adults with cancer. Cancer Control. 2004;11:3-9 7. Panchal SJ, Muller-Schwefe P, Wurzelmann JI, et al. Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden. Int J Clin Pract. 2007;61(7):1181-1187 8. Pappagallo M. Incidence, prevalence and management of opioid bowel dysfunction. Am J Surg. 2001;182 (5A Suppl):11S-18S 9. Smith K et al Prolonged release oxycodone / naloxone tablets: dose proportional pharmacokinetics [abstract]. Proceedings of the 12th World Congress on Pain; 2008 Aug 17-22; Glasgow, UK 10. Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy. A randomized controlled trial. Neurology 2003;60:927-934 11. Riley J, Ross JR, Rutter D. No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients. Support Care Cancer 2006;14:56-64 12. Staahl C, Dimcevski G, Andersen SD, et al. Differential effect of opioids in patients with chronic pancreatitis: An experimental pain study. Scand J Gastroenterol 2007;42;383-90 13. Staahl C, Christrup LL, Andersen SD, et al. A comparative study of oxycodone and morphine in a multi-modal tissue-differentiated pain model. Pain 2006;123:28-36
