Duloxetine Clinical Study Results Show Improvement in Stress Urinary Incontinence in Women
29 July 2004 - 11:01PM
PR Newswire (US)
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. (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO
http://www.newscom.com/cgi-bin/prnh/20040122/BILOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO
http://www.newscom.com/cgi-bin/prnh/20040122/BILOGO DATASOURCE: Eli
Lilly and Company; Boehringer Ingelheim Pharmaceuticals, Inc.
CONTACT: Tammy Hull of Lilly, +1-317-651-9116, ; or Marybeth
McGuire of Boehringer Ingelheim, +1-203-798-4801,
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