INDIANAPOLIS, Jan. 30 /PRNewswire-FirstCall/ -- In a new study, Cymbalta
(duloxetine HCl) 60-120 mg, taken once daily, reduced pain severity
significantly, compared with placebo, in patients with osteoarthritis pain of
the knee. Data from the 13-week randomized, double-blind, placebo-controlled
clinical trial(1) were presented at the annual meeting of the American Academy
of Pain Medicine (AAPM) in Honolulu, Hawaii.
Duloxetine-treated patients showed greater reductions from baseline on the
primary endpoint, the 24-hour average pain score on the Brief Pain Inventory
(BPI), compared with placebo-treated patients. In the study, 65 percent of
duloxetine-treated patients experienced a clinically significant (at least 30
percent) improvement in pain, compared with 44 percent of placebo-treated
patients.
The duloxetine-treated patients also showed improved physical function,
compared with placebo-treated patients, as measured by the Western Ontario and
McMaster Osteoarthritis Index (WOMAC). In this study, patients on duloxetine
did not show statistically significant improvements on the WOMAC pain and
stiffness subscales compared with placebo.
"The disabling nature of osteoarthritis pain can greatly impact a person's
life," said Vladimir Skljarevski, M.D., a study author and medical fellow at
Eli Lilly and Company. "As our population ages, osteoarthritis of the knee is
likely to become an increasing problem."
The most common adverse events in the study (occurred at a rate of greater
than or equal to 5 percent and at least twice the rate of placebo) included
nausea, constipation and excessive sweating (hyperhidrosis). Adverse events
were similar to those seen in previous duloxetine studies.
Additional Study Highlights
-- Compared with patients receiving placebo, patients receiving duloxetine
experienced additional improvements associated with osteoarthritis pain of the
knee, including:
-- Decreased interference from pain in general activity and normal
work, as measured by the BPI Pain Interference (BPI-I) scales.
-- Duloxetine-treated patients did not show statistically
significant improvements compared with placebo-treated patients according to
BPI-I measures of mood, walking ability, relations with other people, sleep,
enjoyment of life and average interference.
-- Weekly mean of the 24-hour average pain severity and worst pain
severity.
-- PGI-Improvement (PGI-I).
-- Duloxetine-treated patients showed statistically significant
improvements compared with placebo as measured by PGI-I at each office visit,
but not at study endpoint.
-- CGI-Severity.
-- A total of 31 patients in the study discontinued due to adverse events
- seven in the placebo-treated group and 24 in the duloxetine-treated group.
It is estimated that 27 million adults in the United States have
osteoarthritis and the prevalence increases with age.(2) Osteoarthritis of the
knee is a common subtype of this disorder, impacting the lives of
approximately 10 million Americans.(2) In addition to pain, other symptoms of
osteoarthritis include aching, stiffness and limited range of motion of the
joint.(3) Duloxetine is being studied to manage the pain associated with this
disorder.
Methods
In this 13-week double-blind trial, patients were at least 40 years of age
without a current diagnosis of major depressive disorder; with no confounding
painful conditions or diagnosis of inflammatory arthritis or autoimmune
disorders; and with no invasive therapy of the knee in the past three months,
knee arthroscopy within the past year or joint replacement of the index knee
at anytime. Patients were randomized to duloxetine (n=128) or placebo (n=128)
and stratified by whether or not they used nonsteroidal anti-inflammatory
drugs. At week seven, patients who showed suboptimal response to the 60 mg (33
patients) dose had their dose increased to 120 mg. The primary efficacy
endpoint of the study was the Brief Pain Inventory (BPI) 24-hour average pain
rating, which was analyzed using a mixed-model repeated measures (MMRM)
approach. Secondary outcomes included the BPI-Severity and Interference items,
weekly mean of the 24-hour worst pain and average pain scores, response rates
on BPI average pain and weekly 24-hour average pain, the Patient Global
Impressions of Improvement, the Western Ontario and McMaster Universities
Index (WOMAC) total and subscales, Clinical Global Impressions of Severity,
health survey Short Form-36 (SF-36) and EuroQoL Questionnaire - 5 Dimension.
About Cymbalta
Serotonin and norepinephrine in the brain and spinal cord are believed to
both mediate core mood symptoms and help regulate the perception of pain.
Based on preclinical studies, Cymbalta is a balanced and potent reuptake
inhibitor of serotonin and norepinephrine that is believed to potentiate the
activity of these chemicals in the central nervous system (brain and spinal
cord). While the mechanism of action of Cymbalta is not known in humans,
scientists believe its effects on depression and anxiety symptoms, as well as
its effect on pain perception, may be due to increasing the activity of
serotonin and norepinephrine in the central nervous system.
Cymbalta is approved in the United States for the acute and maintenance
treatment of major depressive disorder, the acute treatment of generalized
anxiety disorder, the management of diabetic peripheral neuropathic pain and
the management of fibromyalgia, all in adults (18+). Cymbalta is not approved
for use in pediatric patients.
Important Safety Information
Cymbalta is approved to treat major depressive disorder and generalized
anxiety disorder and manage diabetic peripheral neuropathic pain.
Antidepressants can increase suicidal thoughts and behaviors in children,
adolescents and young adults. Patients should call their doctor right away if
they experience new or worsening depression symptoms, unusual changes in
behavior, or thoughts of suicide. Be especially observant within the first few
months of treatment or after a change in dose. Cymbalta is approved only for
adults 18 and over.
Cymbalta is not for everyone. Patients should not take Cymbalta if they
have recently taken a type of antidepressant called a monoamine oxidase
inhibitor (MAOI), are taking Mellaril(R) (thioridazine) or have uncontrolled
glaucoma. Patients should speak with their doctor about any medical conditions
they may have, including liver or kidney problems, glaucoma, or diabetes.
Patients should tell their doctor about all their medicines, including those
for migraine, to avoid a potentially life-threatening condition. Taking
Cymbalta with NSAID pain relievers, aspirin, or blood thinners may increase
bleeding risk. They also should talk to their doctor about their alcohol
consumption. Patients should consult with their doctor before stopping
Cymbalta or changing the dose and if they are pregnant or nursing.
Patients taking Cymbalta may experience dizziness or fainting upon
standing. The most common side effects of Cymbalta include nausea, dry mouth,
sleepiness and constipation.
This is not a complete list of side effects.
For full Patient Information, visit www.cymbalta.com.
For full Prescribing Information, including Boxed Warning and medication
guide, visit http://www.cymbalta.com/.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing
portfolio of first-in-class and best-in-class pharmaceutical products by
applying the latest research from its own worldwide laboratories and from
collaborations with eminent scientific organizations. Headquartered in
Indianapolis, Ind., Lilly provides answers -- through medicines and
information -- for some of the world's most urgent medical needs. Additional
information about Lilly is available at www.lilly.com.
P-LLY
This press release contains forward-looking statements about the potential
of Cymbalta for chronic pain including the management of osteoarthritis pain
of the knee and reflects Lilly's current beliefs. However, as with any
pharmaceutical product, there are substantial risks and uncertainties in the
process of development and commercialization. There is no guarantee that the
product will continue to be commercially successful. For further discussion of
these and other risks and uncertainties, see Lilly's filings with the United
States Securities and Exchange Commission. Lilly undertakes no duty to update
forward-looking statements.
P-LLY
(1) Chappell, A, et al. Duloxetine 60 to 120 mg Once Daily Versus Placebo
in the Treatment of Patients with Osteoarthritis Knee Pain. Poster presented
at the American Academy of Pain Medicine Annual Meeting. 29 January 2009.
(2) Lawrence, RC, et al. Estimates of the Prevalence of Arthritis and
Other Rheumatic Conditions in the United States. 2008. Arthritis and
Rheumatism (58):26-35.
(3) National Pain Foundation Web site -
http://www.nationalpainfoundation.org/MyTreatment/articles/Arthritis_Types.asp
, accessed on 22 December 2008.
(Logo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
