Duloxetine Stress Urinary Incontinence Efficacy and Safety Study

• To assess the efficacy of duloxetine 80 mg/day for 8 weeks in women with stress urinary incontinence (SUI) compared with placebo as measured by the percent change in incontinence episode frequency (IEF) from baseline.
• (Note: For the purposes of this study, SUI is defined as incontinence occurring with effort or exertion or on sneezing or coughing (Abrams et al. 2002).)

• To compare the efficacy of duloxetine with that of placebo as measured by the change in the disease-specific quality of life instrument (I QOL) scores from baseline to endpoint.
• To compare the efficacy of duloxetine with that of placebo in subject perceived improvement in SUI as measured by the Patient’s Global Impressions of Improvement (PGI I) questionnaire.
• To compare the safety of duloxetine with that of placebo in the treatment of SUI based on vital signs, laboratory values, and the occurrence of treatment-emergent adverse events (TEAEs).

Study F1J-MC-SBBU will examine the effect of duloxetine treatment in women with SUI. The inclusion and exclusion criteria of this Phase 3 study will ensure that all subjects have a clinical diagnosis of SUI.

• Drug: Duloxetine
• Drug: Placebo

Inclusion Criteria:

• Present with SUI based on the disease diagnostic criteria, average at least one incontinent episode per day on the screening diary, and have had symptoms of SUI for a minimum of 3 months prior to study entry.
• Are women of non-childbearing potential by reason of hysterectomy, other surgery, or natural menopause, or are women of childbearing potential who test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a medically accepted means of contraception (for example, intrauterine device [IUD], oral or injectable contraceptives, implant, barrier device, sterilization, abstinence, or sex with a vasectomized male partner) for the duration of the study. Women using oral contraceptives or hormone replacement therapy must have a stable dose and regimen for greater than or equal to 3 months prior to entry into the study.
• Are free of UTI symptoms and have a negative urine dipstick for nitrates and leukocyte esterase.
• Have discrete episodes of incontinence (that is, are dry between episodes and not continuously leaking urine, synchronous with increased intra-abdominal pressure from coughing, sneezing, exercising, etc.).
• Have seven (7) or more incontinence episodes per week, urinary diurnal frequency of eight (8) or less per day and nocturia of two (2) or less per day with denial of urge incontinence as a predominant symptom per micturition history collected at Visit 1. An incontinence episode is defined as an easily noticeable leakage of urine that would wet a pad, containment garment, or article of clothing. Diurnal refers to the voiding episodes that occur during the normal awake hours. Nocturia refers to the voiding episodes that occur during the normal sleeping hours and that wake the subject.

Exclusion Criteria:

• Suffer from severe constipation (for example, have impacted rectum at time of physical examination despite recent evacuation).
• Has on physical examination, neurological and/or vaginal examination results which, in the opinion of the investigator, should exclude the subject.
• Are on a medication regimen (including diuretics) for which dose and/or frequency has not been stable for at least 12 weeks prior to randomization, or is anticipated to change during the course of the study.
• Have had any major inpatient surgery within 3 months prior to study entry.

• Have current diagnosis of any of the following conditions, disorders, or diseases of the genito-urinary tract:

  1. Ureteric, bladder, urethral, or rectal fistula
  2. Uncorrected congenital abnormality leading to urinary incontinence
  3. Detrusor instability or noncompliant bladder
  4. Adult enuresis
  5. Voiding difficulty (i.e., subject complains of difficulty emptying their bladder).