PARIS and AACHEN, Germany, June 13 /PRNewswire/ -- Results from two phase III clinical studies of tapentadol immediate release tablets (IR) suggest a significantly improved gastrointestinal tolerability(1) as well as safety(2) profile compared to oxycodone HCl IR. The data were presented by the German pharmaceutical company Grunenthal at this year's Annual Congress of the European League against Rheumatism (EULAR, June 11-14, Paris, France).
In Europe, one in five adults experiences chronic pain(3) in their life. To reduce pain effectively, especially with chronic pain conditions, the use of strong analgesics such as opioids is expanding.(4) However, a substantial number of patients receiving pain therapy do not feel satisfied with their treatment(5),(6),(7) and stop their opioid therapy against medical recommendation.(8) The most important reasons for this are gastrointestinal (GI) side effects like nausea and vomiting in the first few days and constipation in the course of ongoing treatment(9); GI tolerability is one of the leading causes of treatment discontinuation for patients who take prescription pain medications.
Tapentadol is a novel centrally acting analgesic that acts by two mechanisms of action, combining mu-opioid receptor agonism and noradrenaline reuptake inhibition properties in a single molecule. New results from two phase III studies with tapentadol were presented at the EULAR meeting. A study in patients with end-stage joint disease showed that treatment with a 50 mg or 75 mg tapentadol IR resulted in significantly higher pain relief compared to placebo (P<0.001) when assessed over five days of treatment.(1) In addition, patients treated with tapentadol experienced significantly less GI side effects compared to patients treated with 10 mg of oxycodone IR.
The 50 mg and 75 mg tapentadol IR treatment groups showed similar efficacy to that seen in patients treated with 10 mg of oxycodone HCl IR.
The most common adverse events in both treatment groups included nausea, dizziness and vomiting. However, compared to oxycodone IR, both doses of tapentadol studied were associated with a significant reduction in the incidence of gastrointestinal side effects such as nausea, vomiting and constipation. 26 percent of patients treated with 10 mg of oxycodone IR experienced constipation compared to only 4 and 7 percent of the tapentadol IR groups, treated with 50 mg and 75 mg, respectively (P<0.001).
In addition, 18 percent of the patients in the tapentadol IR 50 mg group and 21 percent in the tapentadol IR 75 mg group reported nausea compared to 41 percent in the oxycodone IR group (P< 0.001). There also were fewer reports of vomiting with both doses of tapentadol IR, 50 mg and 75 mg: 7 or 14 percent respectively versus 34 percent with oxycodone IR (P<0.001).
While in the oxycodone HCl IR 10 mg group the discontinuation rate was 29 percent, only 13 and 18 percent of the patients in the tapentadol IR 50- and 75 mg group, respectively, discontinued the treatment before the end of the study.
The second study presented at the EULAR congress further demonstrates the improved tolerability profile of tapentadol IR in comparison to oxycodone HCl IR; for the first time data was collected over a treatment period of 90 days.(2)
The objective of this phase III, randomized 4:1 vs. oxycodone IR, double-blind, flexible dose study was to assess the safety of tapentadol IR for treating low back pain or osteoarthritis pain of the hip or knee over a period of 90 days. Treatment included tapentadol IR (50 or 100 mg) every four to six hours as needed up to 600 mg per day or oxycodone HCl IR (10 or 15 mg) every four to six hours as needed up to 90 mg per day. A total of 679 and 170 patients in the tapentadol IR and oxycodone HCl IR groups, with average pain intensity at inclusion on an 11-point numerical rating scale of 7.0 and 7.2, respectively(10), were included in the efficacy and safety analyses.
Both treatment groups indicated a comparable analgesic effect at the specified doses. The incidences of nausea, vomiting, constipation, and the composite of nausea and/or vomiting in the tapentadol IR group were significantly lower than in the oxycodone HCl IR group (P<0.001 for all treatment comparisons).
Significant differences (P<0.05) were found between the groups for time to first onset of nausea, vomiting, and constipation, with the time-to-event being consistently shorter in the oxycodone HCl IR group.
In conclusion, the two studies showed the high efficacy of tapentadol IR as well as its significantly improved gastrointestinal tolerability profile in comparison to oxycodone IR.
Tapentadol is a next generation centrally-acting analgesic, which is currently being developed for the relief of moderate to severe pain. It has a unique profile with two mechanisms of action, combining mu-opioid receptor agonism and noradrenaline reuptake inhibition properties in a single molecule. It demonstrates an efficacy comparable to classical strong opioids, like oxycodone or morphine, and an improved tolerability profile, especially in regard to gastro-intestinal side effects like nausea, vomiting, and constipation. Tapentadol is being developed as immediate-release formulation for acute pain and prolonged-release formulation for chronic pain; once approved, it will be used in hospital and outpatient settings.
In the United States a New Drug Application (NDA) has been submitted to the U.S. Food and Drug Administration (FDA) for tapentadol immediate release (IR) tablets by Grunenthal's co-development partner Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD). Grunenthal is preparing the submission of tapentadol IR to regulatory authorities in Europe, Mexico, and South America.
Two Mechanisms of Action
Tapentadol acts by two mechanisms of action, combining mu-opioid receptor agonism and noradrenaline reuptake inhibition properties in a single molecule. Mu-receptor agonists are drugs that bind to mu-opioid receptors in the central nervous system. These drugs modify sensory and affective (mood) aspects of pain, inhibit the transmission of pain on the spinal cord level and affect activity in parts of the brain that control how pain is perceived. Noradrenaline reuptake inhibitors are a type of central nervous system medication that increases the level of noradrenaline in the brain by inhibiting its reabsorption into nerve cells; these compounds have analgesic properties.
Tapentadol Co-Development Partnership
Grunenthal discovered and began development of tapentadol. Grunenthal and J&JPRD are conducting the phase IIb and III development programs for tapentadol for acute and chronic pain conditions. Grunenthal licensed rights to tapentadol to Ortho-McNeil-Janssen Pharmaceuticals, Inc., and J&JPRD, for the United States, Canada and Japan. Grunenthal maintains marketing rights in Europe and rest of the world.
Grunenthal is an expert in pain therapy and gynaecology and a pioneer in intelligent, user-friendly drug delivery technologies. Founded in 1946, the company employs 1,900 people in Germany and 4,800 worldwide. In 2006, Grunenthal achieved revenues of 813 million Euro. http://www.grunenthal.com
(1) Upmalis D, Okamoto A, Van Hove I, Stegmann J, Haeussler J. Efficacy and Tolerability Data Supporting the Use of Tapentadol Immediate Release for the Relief of Pain From End-Stage Joing Disease. Abstract AB0744, 9th Annual European Congress of Rheumatology (EULAR 2008), 11-14 June 2008, Paris, France.
(2) Oh C, Upmalis D, Okamoto A, Stegmann J. Flexible Use of Tapentadol Immediate Reelease for 90 Days for the Treatment of Low Back Pain and Osteoarthritis Pain: A Safety Study. Abstract FRI0335, 9th Annual European Congress of Rheumatology (EULAR 2008), 11-14 June 2008, Paris, France.
(3) 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. 2006;10:287-333.
(4) Rowbotham MC, Lindsey CD. How effective is long-term opioid therapy for chronic noncancer pain? Clin J Pain. 2007;23:300-2.
(5) McDermott AM, Toelle TR, Rowbotham DJ, Schaefer CP, Dukes EM. The burden of neuropathic pain: results from a cross-sectional survey. Eur J Pain. 2006;10:127-35.
(6) Eriksen J, Sjogren P, Bruera E, Ekholm O, Rasmussen NK. Critical issues on opioids in chronic non-cancer pain: an epidemiological study. Pain. 2006;125:172-.
(7) OPEN Minds. The white paper on opioids and pain: a pan-European challenge. 2005. Available from: http://www.openmindsonline.org/english/pdf/White_Paper.pdf [Last accessed 09 Apr 2008].
(8) Nicholson B. Responsible prescribing of opioids for the management of chronic pain. Drugs. 2003;63:17-32.
(9) Harris JD. Management of expected and unexpected opioid-related side effects. Clin J Pain 2008; 24: S8-S13.
(10) Oh C., Upmalis D., Okamoto A., Stegmann J. Tapentadol Immediate Release for 90 Days for the Treatment of Low Back Pain and Osteoarthritis Pain: A Safety Study. Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ, USA; Research and Development, Grunenthal GmbH, Aachen, Germany. Poster presented at the 9th Annual European Congress of Rheumatology (EULAR 2008), 11-14 June 2008, Paris, France.
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