Safety and Efficacy Study of Intrasphincteric Autologous Myoblast Injection to Treat Stress Urinary Incontinence

Inclusion criteria

• Female outpatients, predominant clinical diagnosis of SUI
• 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 a positive Fixed Bladder Volume Cough Stress Test (CST) result; and post void residual volume of <50 ml
• Report normal urinary diurnal (≤8/day) and nocturnal (≤2/night) frequency per micturition history
• Have had symptoms of SUI for a minimum of 3 months prior to study entry
• Can independently use toilet without difficulty
• If patients regularly use laxatives, stool softeners, or stool-bulking agents (for example, fibre supplements), the use of these products should remain constant during participation in the study.
• Competent to comprehend, sign, and date an Ethics Committee approved informed consent form before any study-specific procedure is performed.
• 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 enrolment 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.

Exclusion criteria

• Previous diagnosis of any of the following conditions, disorders, or diseases of the urinary tract:

• Greater than Stage I Anterior (cystocoele), Apical (uteri), or Posterior (rectocoele) Compartment Prolepses as per the POP-Q)
• Ureteric bladder, urethral or rectal fistula
• Uncorrected congenital abnormality leading to urinary incontinence
• Interstitial cystitis
• Urinary urgency that results in leakage (as a predominant symptom)
• Adult enuresis
• Urodynamically proven:
• detrusor instability
• sensory urgency defined as first sensation of bladder fill (urge to void) of <100 ml; bladder capacity of <300 ml
• voiding difficulty
• Have no sensation at any time during the simple filling cystometry procedure
• Unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before enrollment
• Have a symptomatic urinary tract infection (UTI); or have a history of four or more urinary tract infections in the preceding year.
• Have prolonged menstruation (>14 days per month).
• Have history of (or currently have) urogenital cancer.
• Suffer from severe constipation defined as less than one bowel movement per week
• Are pregnant, <12 months postpartum or are lactating
• Have had any major inpatient surgery within 3 months prior to study entry
• Known infection with human immunodeficiency virus (HIV)
• Known active infection with Hepatitis B virus, Hepatitis C virus or Lues.
• Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results.
• Have had any anti-incontinence or prolapse surgery, including the following:

• Anterior Repair
• Needle Suspension such as Raz; Pereyra; Stamey; Gittes; and Muzsnai procedures
• Retropubic Procedures: such as Marshall, Marchetti & Krantz; and Burch procedures
• Sling Procedure
• Collagen Injections
• Artificial Sphincter.
• Use any of the following:

• Any anti-incontinence device (for example, Reliance, Minigard, or FemAssist) including tampons used to prevent incontinence during participation in the study
• Vaginal pessaries for prolapse or incontinence
• Any nonpharmacologic intervention for incontinence or prolapse (for example, electro stimulation, vaginal cones, or any such device) within the 3 months prior to study entry.
• Current use of any of the following drugs: antidepressants, duloxetine, monoamine oxidase inhibitors or other, clonidine, alpha-methyl-DOPA, beta-blockers, guanethidine, reserpine, pentosan polysulfate, or alpha-receptor antagonists/agonists (chronic use).
• Current use of any medications for the treatment of urinary incontinence.
• Are on a medication regimen including estrogens, anti-estrogens, or diuretics where dose and/or frequency has not been stable for at least the past 12 weeks, or is anticipated to change during the course of the study.
• ≤ 30 days since receiving an investigational medicinal product or device in another clinical trial. Current enrollment in another clinical trial is not permitted.
• Allergy/ intolerance of at least one of the active ingredients or excipients of the investigational products, e.g. bovine protein, gentamycin
• Have any abuse disorder within the 5 years prior to study entry; e.g. patients who report regular consumption of >21 alcoholic drinks per week (an average of 3 drinks per day)