| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| stress urinary incontinence |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of this study is to assess the effects of duloxetine 40 mg twice
daily (BID) in women with urodynamically proved stress urinary incontinence (SUI) on
the within-group change in vesical Valsalva leak point pressure (VLPP) from baseline to endpoint (4 weeks). |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the within-group endpoint/baseline ratios of Root Mean Square Voltage and Mean Rectified Voltage from the rhabdosphincter electromyogram at rest and with coughing, and the ratio of cough/rest ratios from baseline to endpoint (4 weeks). To evaluate the within-group changes in VLPP and ratios of EMG variables from baseline to 6 months and from 4 weeks to 6 months. To describe the percent change in IEF (incontinence episode frequency) from baseline to postbaseline and define two groups, responders and non-responders, based on the threshold value of <50% IEF reduction values. To compare the changes in VLPP and in EMG ratios from baseline to 4 weeks and from baseline to 6 months in responders and non-responders. To evaluate the safety and tolerability of duloxetine 40 mg BID for up to 28 weeks in subjects diagnosed with urodynamic stress incontinence (USI). Safety and tolerability will be evaluated based on TEAEs, discontinuation rates, vital signs, and laboratory analyses. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal 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). |
|
| E.4 | Principal 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 excluded medications within 14 days prior to study entry or at any time during the study.
[37] Have any active substance abuse disorder within the 5 years prior to
study entry; subjects who report regular consumption of >=21 alcoholic
drinks per week (an average of 3 drinks per day) will be excluded.
[38] Have previously entered any study investigating duloxetine.
[39] Are investigator site personnel directly affiliated with the study, or are
immediate family of investigator site personnel directly affiliated with
the study. Immediate family is defined as a spouse, parent, child, or
sibling, whether biological or legally adopted.
[40] Are employed by Lilly or Boehringer Ingelheim.Immediate family of Lilly or BI employees may participate in Lilly-sponsored clinical trials, but are not permitted
to participate at a Lilly facility. Immediate family is defined as a
spouse, parent, child, or sibling, whether biological or legally adopted.
[41] Have received treatment within the last 30 days with a drug that has
not received regulatory approval at the time of study entry.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary outcome measure will be vesical VLPP. The primary outcome variable will
be the change in VLPP from Visit 2 to Visit 3. The primary analysis will be the Wilcoxon signed-rank test on the primary outcome variable. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| last visit of the last subject undergoing the trial |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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