Effect of Duloxetine on Valsalva Leak Point Pressureand Quantitative Rhabdosphincter ElectromyographyMeasures in Women with Stress Urinary Incontinence

Phase 1

Conditions: stress urinary incontinence

Registration Number: EUCTR2004-004160-67-DK

Lead Sponsor: Eli Lilly and Company Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 93

Inclusion Criteria

Subjects may be included in the study only if they meet all of the following criteria:
[1] Are female outpatients.
[2] Are =18 and =75 years of age.
[3] Have a diagnosis of only stress urinary incontinence (SUI)
(urodynamic stress incontinence [USI] with normal compliance and no
detrusor overactivity [DO]) confirmed on urodynamic studies (UDS)
(determined at Visit 2; see Section 3.2.2.1) and a positive Valsalva
leak point pressure (VLPP).
[4] Have discrete episodes of incontinence (that is, are dry between
episodes and not continuously leaking urine), synchronous with
increased abdominal pressure from coughing, sneezing, exercising,
etc. An episode is defined as an easily noticeable leakage of urine that
would wet a pad, containment garment, or article of clothing.
[5] Are ambulatory and able to use a toilet independently and without
difficulty.
[6] Have no language or cognitive barriers, agree to comply with the
requirements of the protocol, and sign a written informed consent
document (ICD) prior to entry into the study.
[7] Are women of non-childbearing potential by reason of hysterectomy,
other surgery, or natural menopause, or are women of childbearing
potential agreeing 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 =3 months prior to entry into
the study.
[8] Have no pelvic organ prolapse protruding more than 1 cm beyond the
hymen (Bump et al. 1996).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

[9] At Visit 1, have a positive urine culture (>100,000 cfu/mL), or a history of four or more urinary tract infections in the preceding year.
[10] Have spinal cord lesions, multiple sclerosis, or other major central
nervous system (CNS) abnormalities that affect the lower urinary tract.
[11] Suffer from severe constipation (have a history of fecal impaction or
have impacted rectum at time of physical examination despite recent
evacuation).
[12] Are on a regimen of a chronically administered medication where dose
and/or frequency has not been stable for at least 3 months prior to
randomization, or is anticipated to change during the course of the
study.
[13] Have had urethral surgery (for example, diverticulectomy, urethral
dilations, or bulk injections).
[14] Have had more than one continence surgery.
[15] Have had any major surgery or continence surgery within 6 months
prior to study entry.
[16] Have current diagnosis of any of the following conditions, disorders,
or diseases of the genitourinary tract: a. Ureteric, bladder, urethral, or rectal fistula;
b. Uncorrected congenital abnormality leading to urinary incontinence; c. Adult enuresis or voiding difficulty.
[17] Use any of the following currently or at any time during the study:
a. Any anti-incontinence device including tampons used to prevent incontinence
b. Any medication in the list of excluded medications
[18] Have used any pharmacologic (including duloxetine for any reason) or
nonpharmacologic (such as electrostimulation, vaginal cones, or any
device) intervention for incontinence or prolapse within 3 months prior
to study entry or throughout the study.
[19] Began pelvic floor muscle exercises within 6 months prior to study entry. Subjects who regularly perform pelvic floor muscle exercises cannot change their
exercise regimen during the course of the study.
[20] Have current or past urogenital cancer.
[21] Have any condition, limitation, disease, or abnormal laboratory value
that could, in the judgment of the investigator, preclude evaluation of
response to duloxetine.
[22] On physical examination, have neurological and/or vaginal
examination results that, in the opinion of the investigator, should
exclude the subject.
[23] Are known to have increased intraocular pressure or to be at risk for
acute narrow-angle glaucoma.
[24] Have a symptomatic arrhythmia despite antiarrhythmic medication.
[25] Have current angina or any active cardiac ischemic condition,
including myocardial infarction, within 6 months prior to study entry.
[26] Have uncontrolled or poorly controlled hypertension.
[27] Have active seizure disorder.
[28] Have unstable diabetes mellitus.
[29] Have a known hypersensitivity to duloxetine or any of the inactive
ingredients.
[30] Have a history of severe allergies, including drug allergies, requiring
emergency medical treatment or have multiple and/or severe adverse
drug reactions.
[31] Have a history of ongoing episodic lung disease associated with four
or more acute exacerbations of severe coughing per year.
[32] Have acute liver injury (such as hepatitis) or severe (Child-Pugh Class C) cirrhosis.
[33] Are pregnant, have been pregnant in the previous 6 months, or have
not resumed normal menstruation for 3 months prior to study entry due
to breastfeeding.
[34] Are breastfeeding.
[35] Use monoamine oxidase inhibitors (MAOIs) within 14 days of
randomization or potential need to use an MAOI during the study or
within 5 days of discontinuing study drug.
[36] Use