Duloxetine Significantly Reduced Osteoarthritis Knee Pain in New Study

Indianapolis, U.s.a. and Ingelheim, Germany (ots/PRNewswire)
--

- Patients on Treatment Also Experienced Improved Physical
Functioning

In a new study, duloxetine hydrochloride (Cymbalta(R)),
administered at 60 mg to 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, 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.

"With an aging population, the number of people with
osteoarthritis of the knee is expected to rise," said Jacques P.
Brown, M.D., of the Rheumatology and Bone Diseases Research Group in
Quebec City, Canada. "This condition can have a real impact on a
person's life, limiting functionality and ability to perform
day-to-day activities."

The most common adverse events in the study (occurred at a rate
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.

Osteoarthritis is the most common form of arthritis and the most
frequent cause of joint disease, which affects more than 5 percent of
all adults worldwide.(2) Almost 80 percent of patients with
osteoarthritis have some degree of limitation of movement, and 25
percent cannot perform their major daily activities of life.(3) In
addition to pain, other symptoms of osteoarthritis include aching,
stiffness and limited range of motion of the joint.(4)

In Europe, duloxetine is approved for the treatment of diabetic
peripheral neuropathic pain (DPNP), major depressive disorder (MDD)
and generalised anxiety disorder (GAD).

Duloxetine is approved in various countries outside of Europe for
the management of DPNP, for the treatment of MDD, for the treatment
of GAD and for the management of fibromyalgia.

Notes to Editors:
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-treated patients 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.

Methods

In this 13-week double-blind trial, patients were at least 40
years of age without a current diagnosis of major depressive
disorder; no confounding painful conditions, diagnosis of
inflammatory arthritis or autoimmune disorders; and 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 Duloxetine

While duloxetine's mechanism of action in humans is not fully
known, it is believed to affect both serotonin and
norepinephrine/noradrenaline-mediated nerve signaling in the brain
and the spinal cord. Based on preclinical studies, duloxetine is a
reuptake inhibitor of serotonin and norepinephrine/noradrenaline.
Scientists believe its effect on mood and pain perception is due to
increasing the activity of serotonin and norepinephrine in the
central nervous system.

Duloxetine is approved for the treatment of major depressive
disorder and diabetic peripheral neuropathic pain in many countries
and is also approved in some countries for the treatment of stress
urinary incontinence and generalised anxiety disorder and the
management of fibromyalgia. Duloxetine is approved only for adults 18
and over. There is a possibility of an increased risk of suicidal
thoughts or behavior in children and young adults treated with
antidepressants. Patients should call their doctor right away if they
experience worsening depression symptoms, unusual changes in behavior
or thoughts of suicide, especially at the beginning of treatment or
after a change in dose.

Patients taking duloxetine may experience dizziness or fainting
upon standing. The most common side effects of duloxetine include:

-- For depression: Dry mouth, nausea, diarrhea, headache, insomnia
-- For diabetic peripheral neuropathic pain: Nausea, fatigue, dizziness,
headache, somnolence (sleepiness)
-- For generalised anxiety disorder: Dry mouth, nausea, fatigue,
dizziness, headache, somnolence (sleepiness)
-- For stress urinary incontinence: Constipation, dry mouth, nausea,
fatigue
-- For fibromyalgia: Constipation, dry mouth, nausea, diarrhea, fatigue,
decreased appetite, dizziness, headache, somnolence (sleepiness),
insomnia

This is not a complete list of side effects.

Duloxetine is contraindicated in patients who are allergic to it,
who have liver disease resulting in hepatic impairment, who are
taking a monoamine oxidase inhibitor (MAOI), fluvoxamine,
ciprofloxacin or enoxacine or who have severe kidney disease. The
initiation of treatment with duloxetine also is contraindicated in
patients with uncontrolled hypertension that could expose patients to
a potential risk of hypertensive crisis.

Eli Lilly and Company and Boehringer Ingelheim

In November 2002, Eli Lilly and Company and Boehringer Ingelheim
signed a long-term agreement to jointly develop and commercialize
duloxetine hydrochloride. This partnership covers neuroscience
indications in most countries outside of the United States and Japan,
with few exceptions.

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. For more information please visit
www.lilly.co.uk.

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it
operates globally with 135 affiliates in 47 countries and almost
38,900 employees. Since it was founded in 1885, the family-owned
company has been committed to researching, developing, manufacturing
and marketing novel products of high therapeutic value for human and
veterinary medicine. In 2007, Boehringer Ingelheim posted net sales
of 10.9 billion euro while spending one fifth of net sales in its
largest business segment Prescription Medicines on research and
development. For more information please visit
www.boehringer-ingelheim.com.

Duloxetine for major depressive episodes, diabetic peripheral
neuropathic pain, and generalised anxiety disorder is marketed by
Lilly and Boehringer Ingelheim in all countries included in the
partnership under the brand name Cymbalta(R), except for Greece,
Italy and Spain. In Greece, Italy and Spain, Lilly markets the
product as Cymbalta(R) and Boehringer Ingelheim markets the product
as Xeristar(R). In addition, in Germany, Lilly and Boehringer
Ingelheim market duloxetine for diabetic peripheral neuropathic pain
as Ariclaim(R). In the United States, Cymbalta(R) is marketed by
Lilly and Quintiles. In Japan, duloxetine is co-developed and
co-marketed by Lilly and Shionogi & Co., Ltd.

Duloxetine for stress urinary incontinence is marketed by Lilly
under the brand name Yentreve(R).

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.

References

(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) PHG Foundation. Osteoarthritis. Genomics and Population
Health. Available on: http://www.phgfoundation.org/news/893/,
accessed on 19 January 2009.

(3) The World Health Organisation, 50 Facts: Muskoskeletal
Disorders. WHO. Available on:
http://www.who.int/whr/1997/media_centre/50facts/en/, accessed on 19
January 2009.

(4) Types of Arthritis Pain. The National Pain Foundation.
Available on: http://www.nationalpainfoundation.org/MyTreatment/artic
les/Arthritis_Types.asp, accessed on 19 January 2009.

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ots Originaltext: Eli Lilly and Company
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Contact:
Sonja Popp-Stahly of Eli Lilly and Company, +1-317-655-2993,
spopp-stahly@lilly.com; John Pugh, Boehringer Ingelheim,
+49-(6132)-77-2964, john.pugh@boehringer-ingelheim.com / Photo:
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