Duloxetine Clinical Study Results Show Improvement in Stress Urinary Incontinence in Women

Duloxetine Clinical Study Results Show Improvement in Stress
Urinary Incontinence in Women 


SAN DIEGO, July 29  /PRNewswire-FirstCall/ -- A study presented today shows
that women who transitioned from placebo to duloxetine in an open-label study
reported similar improvement to that of women who took duloxetine during the
preceding 12 weeks in a double-blind study.(1)  Duloxetine hydrochloride is an
investigational agent being developed under the trade name Yentreve(TM)* for
the treatment of stress urinary incontinence (SUI), the accidental urine
leakage during physical activities such as sneezing, coughing, laughing,
lifting or exercising.  Study results were presented at a scientific meeting
organized by the American Urogynecological Society (AUGS) and the Society of
Gynecological Surgeons (SGS).

The post-hoc analysis evaluated whether women in a randomized, double- blind
study who transitioned from a placebo to duloxetine therapy in the open- label
extension would perceive similar improvement when compared to women who took
duloxetine throughout both periods.  An open-label extension is not a
controlled study, and patients knew they were taking duloxetine.

"The study results show that duloxetine can significantly improve SUI symptoms
in women," said David Muram, M.D., medical advisor for Eli Lilly and Company,
discussing the poster presentation of the data at the AUGS/SGS meeting.  "What
was most exciting about this study is that women who took placebo in the first
phase of the study and then transitioned to duloxetine in the open-label phase
perceived similar improvements in their condition to those who took duloxetine
in both phases."

SUI is an embarrassing and bothersome medical condition that affects nearly 15
million adult women in the United States and can have a significant impact on
quality of life.(2,3,4)  With nearly twice the prevalence of urge incontinence,
SUI is the most common form of urinary incontinence among women.(2,5)  Although
common, it is a medical condition that is not normal at any age; unfortunately,
many women do not seek treatment because they are embarrassed, fear surgery, or
believe that it is a normal part of aging and that nothing can be done about
it.  The primary causes of SUI are weakness of the urethral sphincter and/or
diminished pelvic support of the bladder and urethra.  Risk factors include
obesity, chronic coughing, constipation and childbirth.(6)

About the Study

The post-hoc analysis of a phase III North American study evaluated the
improvement in 493 women with SUI who continued to an open-label treatment with
duloxetine.  Following a two-week lead-in period with a single-blind placebo,
the subjects were randomized to either 40 mg duloxetine twice a day or placebo.
 After 12 weeks of blinded therapy, women who were taking duloxetine or placebo
had the option of entering an open-label extension phase in which all subjects
received 40 mg duloxetine twice a day.  The results as measured by Patient
Global Impression of Improvement scores (PGI-I) included:

* After four weeks, the percentage of women who transitioned from placebo to
duloxetine and rated their condition as being better increased from 41.9
percent (as measured in the double-blind phase) to 67.2 percent (p < 0.001).

* At 12 weeks, there was no significant difference in the percentage of women
reporting improvement (80 percent vs. 77.5 percent, p = 0.61) between those who
had received only duloxetine versus those who had received placebo in the
double-blind phase and then transitioned to duloxetine.

Clinical studies of duloxetine for the treatment of SUI have shown the most
commonly reported adverse events (incidence of >/= 5 percent and at least twice
the placebo rate) reported by patients receiving duloxetine have been nausea,
dry mouth, fatigue, insomnia, constipation, headache, dizziness, somnolence
(drowsiness) and diarrhea.(7)

Duloxetine is a balanced dual reuptake inhibitor of the neurotransmitters
serotonin and norepinephrine,(8) which play a key role in normal urethral
sphincter closure, the weakening of which can result in SUI.  By increasing
neurotransmitter concentration, duloxetine is believed to increase the tone and
contraction of the external urethral sphincter,(9) which helps prevent
accidental urine leakage during physical activities such as sneezing, coughing,
laughing, lifting or exercise.

About Yentreve(TM)*

Yentreve(TM)* is a balanced dual reuptake inhibitor of the neurotransmitters
serotonin and norepinephrine based on preclinical studies.(8)  Yentreve(TM)* is
believed to affect SUI by blocking the reuptake of serotonin and norepinephrine
in the spinal cord, and the increase in the neurotransmitters in turn
stimulates increased activity of the pudendal nerve that controls the external
urethral sphincter.(9)  This stimulation is believed to increase contraction of
the external urethral sphincter, thereby helping prevent accidental urine
leakage with physical activity.

The U.S. Food and Drug Administration issued an approvable letter for
Yentreve(TM)* in September 2003.

About Eli Lilly and Boehringer Ingelheim

In November 2002, Eli Lilly and Company and Boehringer Ingelheim signed a
global long-term agreement to jointly develop and commercialize duloxetine
hydrochloride for the treatment of stress urinary incontinence (SUI) and
depression.  This partnership covers most countries worldwide with few
exceptions.  In the U.S., the collaboration focuses on SUI.

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, IN, Lilly provides answers -- through medicines and information
-- for some of the world's most urgent medical needs.  Additional information
about Lilly is available on http://www.lilly.com/ .

Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the
largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT)
and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim Corporation is one of the world's 20 leading
pharmaceutical companies.  Headquartered in Ingelheim, Germany, it operates
globally with 152 affiliates in 45 countries and more than 34,000 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 2003, Boehringer Ingelheim posted net US sales of $8.37 billion (7.4 billion
euro) while spending more than one fifth of net sales in its largest business
segment -- prescription medicines -- on research and development.

For more information please visit http://www.boehringer-ingelheim.com/ .

This press release contains forward-looking statements about the potential of
duloxetine for the treatment of stress urinary incontinence and reflects
Lilly's current beliefs.  However, as with any pharmaceutical product under
development, there are substantial risks and uncertainties in the process of
development and/or regulatory review.  There is no guarantee that the product
will receive regulatory approvals and any indication for which it is approved
will be determined at the discretion of the Food and Drug Administration. There
is also no guarantee that the product will prove 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.

*  Yentreve is a trademark of Eli Lilly and Company.  This trademark is pending
approval by the FDA as a proprietary drug name for the established name,
duloxetine hydrochloride.

REFERENCES

1.  Siddhanti, S, Liu C, Meadows E, and Muram D. Efficacy of blinded and
open-label treatment of stress urinary incontinence (SUI) with duloxetine.
Poster presented at the American Urogynecological Society and the Society of
Gynecological Surgeons, San Diego, California. July 29, 2004.

2.  Hampel C, Wienhold D, Benken N, Eggersmann C, Thuroff T. Definition of
overactive bladder and epidemiology of urinary incontinence. Urology.
1997;50(suppl 6A):4-14.

3.  Diokno A, Burgio K, Fultz N, Kinchen K, Obenchain R, and Bump R. Medical
and self-care practices reported by women with urinary incontinence. Am J
Managed Care. 2004;10:69-78. The estimate of STRESS URINARY INCONTINENCE
prevalence was derived from Diokno et al and based on STRESS URINARY
INCONTINENCE prevalence as determined by Hampel et al and by Diokno et al.

4.  US Census 2000 Briefs (Age & Gender), US Department of Commerce Web site.

5.  Fultz NH, Burgio, K, Diokno A, Kinchen K, Obenchain R, and Bump R. Burden
of stress urinary incontinence for community-dwelling women. Am J Obstet
Gynecol. 2003; 189: 1275-1282.

6.  Bump R, Norton P. Epidemiology and natural history of pelvic floor
dysfunction.  Obstet and Gynecol Clin of North Am. 1998; 25(04): 723 - 746.

7.  Hurley D, Turner C, Baygani S, Yalcin I, and Viktrup L. Duloxetine for
stress urinary incontinence: A meta-analysis of safety.  Poster presented at
the International Federation of Gynaecology and Obstetrics (FIGO) World
Congress, Santiago, Chile. 2-7 November 2003.

8.  Bymaster F, Dreshfield-Ahmad L, Threlkeld P, Shaw J, Thompson B, Nelson D,
et al. Comparative affinity of duloxetine and venalfaxine for serotonin and
norepinephrine transporters in vitro and in vivo, human serotonin receptor
subtypes, and other neuronal receptors. Neuropsychopharmacolog.
2001;25(6):871-880.

9.  Thor K, Katofiasc M. Effects of duloxetine, a combined serotonin and
norepinephrine reuptake inhibitor, on central neural control of lower urinary
tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther.
1995; 274:1014-1024.

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DATASOURCE: Eli Lilly and Company; Boehringer Ingelheim Pharmaceuticals, Inc.



CONTACT:  Tammy Hull of Lilly, [phone],  ; or

Marybeth McGuire of Boehringer Ingelheim, [phone],

 

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