Paris, France / Aachen, Germany (ots) - 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
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
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.
About Tapentadol 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
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
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.
About Grunenthal 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. 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:
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, Grünenthal GmbH, Aachen, Germany. Poster presented at
the 9th Annual European Congress of Rheumatology (EULAR 2008), 11-14
June 2008, Paris, France.
ots Originaltext: Grünenthal GmbH
Im Internet recherchierbar: http://www.presseportal.ch
Dr. Nicole Foellmer
Phone: +49 241 569-2858,
Fax: +49 241 569-52858,
52099 Aachen, Germany,