Safety Study of hMaxi-K Gene Transfer to Treat Overactive Bladder and Detrusor Overactivity

A Phase 1 Multicenter Study Evaluating the Safety and Potential Activity Of Three Escalating Doses of hMaxi-K Gene Transfer In Female Participants With Overactive Bladder Syndrome and Detrusor Overactivity: Double Blind, Imbalanced Placebo Controlled Design Within 3 Sequential Active Treatment Groups

The purpose of this study is to evaluate the safety of a new product that uses human gene transfer (called hMaxi-K) when it is given to patients with overactive bladder. Human gene transfer is a new type of therapy that is the process of placing genetic material (DNA or RNA) into a person. The primary objective of this study is to evaluate safety parameters occurring subsequent to administration of a single intravesical instillation of study drug.

Two different dose groups of hMaxi-K will be tested in this study: 5000 and 10000 micrograms. A 15000 microgram group was planned; however, the study was terminated before participants were dosed. hMaxi-K will be given as a single administration into the bladder through a catheter. Each women's participation in the study will last for up to 24 weeks (followed by an additional 18-month follow-up period).

The safety parameters to be monitored include: adverse events, clinical laboratory tests, electrocardiograms, and physical examinations.

The secondary objective is to evaluate the efficacy of a single intravesical instillation of hMaxi-K compared to the control group. Efficacy parameters that will be evaluated are: mean number of micturitions per 24 hours, mean number of urge incontinence episodes per 24 hours, mean number of urgency episodes per 24 hours, overall maximum bladder capacity, number of uninhibited contractions during the cystometry procedure, participant rating of urgency score, participant rating of perceived bladder condition severity, participant assessment of response to treatment, participant rating of Quality of Life (Kings Health Questionnaire), SF-12 Health Survey, International Consultation on Incontinence Questionnaire (ICIQ-SF), and pad weight measurement of accidental bladder leaks.

Inclusion Criteria:

• Healthy women of 18 years of age or older and of non-childbearing potential

• Clinical symptoms of overactive bladder for 6 months or longer including at least one of the following:

  1. frequent urination (that is, having to go to the bathroom 8 or more times per day);
  2. symptoms of urinary urgency, which is experiencing a sudden need to pass urine that is difficult to hold back; or the complaint of waking at night two ore more times to urinate;
  3. urge urinary incontinence, which is the complaint of leakage of urine that cannot be stopped, accompanied by or immediately preceded by urgency 5 or more times per week.

• Non-response or poor tolerance to previous treatment for symptoms of overactive bladder and do not wish to continue with that treatment.

Exclusion Criteria:

• A woman with a positive serum (HCG) pregnancy test or who is lactating
• History of three or more culture-documented recurrent urinary tract infections per year
• Current history or previous diagnosis of painful bladder syndrome (interstitial cystitis) with pain in the region of the pelvis, perineum, or lower abdomen relieved by voiding
• Current history of neurological bladder dysfunction
• A life expectancy of less than 12 months
• Current history of Grade 2 or greater cystocele
• An indwelling urethral catheter or need for clean intermittent self- catheterization
• Recent heart attack
• Uncontrolled diabetes
• Latex allergy
• Stress urinary incontinence as determined by observation of the participant coughing while standing with a full bladder and/or response of 2 or 3 on the following Stress Urinary Incontinence question: Do you experience leakage when laughing, coughing, lifting heavy objects or other types of discreet, moderately intense activities? 0=NONE: No leakage. 1=MILD: Minimal leakage on rare occasions during these types of activities; easily tolerated; do not use pads for this. 2=MODERATE: Enough leakage that it requires occasional use of pads and may interfere with usual activity and tasks. 3=SEVERE: Extreme leakage and discomfort that stops all activity and tasks and requires the use of pads on all occasions