Phase 1 Double Blind, Placebo Controlled Study Assessing Safety and Activity Of 2 Escalating Doses of hMaxi-K Gene Transfer By Direct Injection Into the Bladder Wall In Female Subjects With OAB
Overview
- Phase
- Phase 1
- Intervention
- Placebo (PBS-20% sucrose)
- Conditions
- Overactive Bladder
- Sponsor
- Urovant Sciences GmbH
- Enrollment
- 13
- Locations
- 3
- Primary Endpoint
- Number of participants with any treatment-emergent adverse event during the Safety Follow-up Period
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The primary objective of this study is to evaluate the safety of a single treatment of hMaxi-K compared to placebo (PBS-20% sucrose) administered by direct bladder wall injections. Two dose levels (16000 µg and 24000 µg; 20 or 30 bladder wall injections, respectively) in females with moderate Overactive Bladder/Detrusor overactivity (OAB/DO) of ≥6 months duration will be evaluated. In each dose level, 6 participants will receive hMaxi-K and 3 will receive placebo.
Detailed Description
This is a Phase 1 double-blind, placebo-controlled study assessing the safety and activity of 2 escalating doses of hMaxi-K gene transfer by direct injection into the bladder wall in female participants with OAB/DO. 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 multiple intramuscular injections of hMaxi-K compared to the control group. Efficacy parameters that will be evaluated are: number of micturitions per 24 hours, volume per micturition, incontinence episodes, pad weight measurement of accidental bladder leaks, uninhibited contractions during cystoscopy and other cystoscopic evaluations, and general and bladder-specific quality of life assessments (Kings Health Questionnaire, SF-12 Health Survey, and International Consultation on Incontinence Questionnaire \[ICIQ-SF\]).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy women of ≥18 years of age and non-childbearing potential
- •Symptoms of overactive bladder for ≥6 months including at least one of the following:
- •Frequent micturition ≥8 times per 24 hours
- •Urinary urgency or nocturia
- •Urge urinary incontinence five or more incontinence episodes per week
- •Detrusor overactivity with ≥1 uncontrolled phasic contraction(s) of the detrusor of at least 5 centimeters/H20 pressure documented on cystometry at Screening Visit 1A
- •Residual urine volume of ≤200 milliliters (ml)
- •Non-response or poor tolerance to previous treatment for symptoms of OAB/urinary incontinence and do not wish to continue these treatments
- •Have screening laboratory values and electrocardiogram that are within the normal range
- •Able to understand study requirements (i.e., literate in English), give written informed consent, and comply with all study procedures and requirements.
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
Arms & Interventions
Placebo (PBS-20% sucrose)
PBS-20% sucrose administered during two single-treatment dose levels (16000 micrograms \[µg\] and 24000 µg) by direct bladder wall intramuscular injections, 20 to 30 injections depending on active dose comparator.
Intervention: Placebo (PBS-20% sucrose)
hMaxi-K 16000 µg
Single treatment (16000 µg by 20 intramuscular injections). A total of 6 participants will receive hMaxi-K, and 3 will receive placebo.
Intervention: hMaxi-K
hMaxi-K 24000 µg
Single treatment (24000 µg by 30 intramuscular injections). A total of 6 participants will receive hMaxi-K, and 3 will receive placebo.
Intervention: hMaxi-K
Outcomes
Primary Outcomes
Number of participants with any treatment-emergent adverse event during the Safety Follow-up Period
Time Frame: 18 months
Number of participants with any clinically significant electrocardiogram finding during the Treatment Period
Time Frame: 6 months (24 weeks) per participant
Number of participants with any clinically significant electrocardiogram finding during the Safety Follow-up Period
Time Frame: 18 months
Number of participants with any clinically significant clinical laboratory test value during the Treatment Period
Time Frame: 6 months (24 weeks) per participant
Number of participants with any clinically significant clinical laboratory test value during the Safety Follow-up Period
Time Frame: 18 months
Number of participants with any treatment-emergent adverse event during the Treatment Period
Time Frame: 6 months (24 weeks) per participant
Number of participants with any clinically significant physical examination finding during the Treatment Period
Time Frame: 6 months (24 weeks) per participant
Number of participants with any clinically significant physical examination finding during the Safety Follow-up Period
Time Frame: 18 months
Secondary Outcomes
- Change from Baseline in the number of micturitions per day(Baseline; 6 months (24 weeks) per participant)
- Change from Baseline in uninhibited contractions during cystoscopy(Baseline; 6 months (24 weeks) per participant)
- Change from Baseline in the participant rating of the Kings Health Questionnaire (KHQ) score(Baseline; 6 months (24 weeks) per participant)
- Change from Baseline in incontinence episodes(Baseline; 6 months (24 weeks) per participant)
- Change from Baseline in the volume of micturitions(Baseline; 6 months (24 weeks) per participant)
- Change from Baseline in pad weight(Baseline; 6 months (24 weeks) per participant)
- Change from Baseline in the International Consultation on Incontinence Questionnaire-Short Form score(Baseline; 6 months (24 weeks) per participant)
- Change from Baseline in the Short Form-12 (SF-12) score(Baseline; 6 months (24 weeks) per participant)