Duloxetine Reduces Stress Urinary Incontinence in Phase III Study.

Business Editors/Health/Medical Writers

INDIANAPOLIS & RIDGEFIELD, Conn.--(BUSINESS WIRE)--Sept. 10, 2003

First potential pharmaceutical for Stress Urinary Incontinence (SUI)

also shows improvement in meaningful quality of life measures

Duloxetine significantly reduced the number of weekly incontinence episodes among women with stress urinary incontinence (SUI), according to a Phase III study published today in the Journal of Urology. Additionally, women on duloxetine experienced significant improvements in quality of life measures, when compared with women taking placebo.

SUI, a medical condition which affects approximately 30 million (1 in 3) American women over the age of 18(i), is attributable to a decreased urethral sphincter muscle function (at the bladder outlet), whereby accidental urine leakage results from an increase in abdominal pressure. This may be caused by normal actions such as laughing, coughing, sneezing, lifting or exercising. Once approved for use by regulatory agencies, duloxetine will become the first pharmaceutical treatment indicated to reduce the frequency of SUI episodes.

The Phase III data are consistent with previously published Phase II data and provide further support for duloxetine as a pharmacological agent for the treatment of SUI.

"These data are important for physicians and sufferers as there are currently no pharmaceutical options for the millions of women affected by SUI. A pharmaceutical option would be a welcomed choice," said Roger Dmochowski, MD, Professor of Urology in the Department of Urology at Vanderbilt University, Nashville, TN, and a principal investigator in this study.

Study Results

-- The results showed that duloxetine 80 mg, taken as 40 mg twice

daily, significantly reduced the frequency of incontinence

episodes by 50 percent versus 27 percent for placebo in women

with SUI. Reduction of incontinent episodes is the medically

recognized measurement of treatment efficacy.

-- Furthermore, 51 percent of all women taking duloxetine

experienced a 50 percent to 100 percent reduction in frequency

of incontinence episodes.

-- The improvements with duloxetine were not a result of more

frequent voiding by the patients, in that the average time

between voids (emptying of the bladder) was not decreased, but

even increased overall by 20 minutes in the duloxetine group

compared with 2 minutes in the placebo group

-- In addition, the significant duloxetine treatment response was

unaffected by baseline incontinence severity (based on the

number of incontinence episodes at the start of the study).

Women experiencing 14 or more leakage episodes per week at

baseline experienced a similar percentage reduction in their

leakages as women experiencing fewer than 14 episodes per week

at baseline.

-- The most commonly reported side effects with duloxetine in

this study (incidence of greater than or equal to 10.0 percent

and at least twice placebo) were: nausea, fatigue, dry mouth,

insomnia, constipation and dizziness. After the first month of

therapy, the incidence of these adverse events did not differ

significantly between duloxetine- and placebo-treated

patients.

Quality of Life Results

Of particular interest to many women, patients on duloxetine in this study also reported improvements on incontinence-specific scales used to measure effects on their quality of life. Patients taking duloxetine had significantly better improvements in their quality of life scores compared with patients taking placebo using a validated incontinence quality of life question survey. Based on the Patient Global Impression of Improvement (PGI-I) Scale, 62.0 percent of duloxetine-treated subjects rated their condition improved compared with 39.6 percent of placebo-treated women.

Study methodology

The Phase III double-blind placebo-controlled study performed in the United States and Canada enrolled a total of 683 women aged 22-84 years. All women had predominant SUI symptoms and experienced at least seven episodes of incontinence per week. Incontinence symptoms had to be present for a minimum of three months for a woman to be eligible for the study. The trial lasted 12 weeks. One primary measure of efficacy used by researchers was the incontinence episode frequency recorded by patients on real-time diaries. A second primary measure was the total score from the validated Incontinence Quality of Life (I-QOL) questionnaire. Additional measures included voluntary voiding frequency, the Patient Global Impression of Improvement (PGI-I) Scale and three I-QOL subscale scores.

About duloxetine

Duloxetine is a potent dual reuptake inhibitor of the neurotransmitters serotonin and norepinephrine. Duloxetine 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 nerve that stimulates the urethral sphincter. This stimulation is believed to increase contraction of the urethral sphincter at the opening of the bladder, thereby helping prevent accidental urine leakage with physical activity.

The U.S. Food and Drug Administration recently issued an approvable letter for duloxetine for SUI.

About Stress Urinary Incontinence

SUI, with nearly twice the prevalence as urge incontinence, is the most common form of urinary incontinence among women. In the United States alone it affects approximately 30 million women over the age of 18(i). Although common, SUI is a medical condition that is not normal at any age, but unfortunately many women do not seek treatment because they are embarrassed, fear surgery, or believe it is a normal part of aging and that nothing can be done about it. Primary causes of SUI are nerve damage, muscle damage or weakness, and damage to the support of the bladder and urethra. Risk factors include childbirth, obesity, chronic coughing and constipation.

About Eli Lilly 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