Extended-Release Oxybutynin for the Treatment of Neurogenic Detrusor Overactivity

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects and tolerability (how well a participant can stand a particular medicine or treatment) of flexible dose Oxybutynin Extended-Release (OXY-ER, Lyrinel) including safety and quality of life assessment in participants with neurogenic detrusor overactivity (NDO - the nerves mediating the detrusor muscle do not work properly leading to frequent feeling of need to urinate during the day, night, or both).

Detailed Description
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This is an open-label (all people know the identity of the intervention), single arm, prospective (study following participants forward in time), multi-center study of participants with NDO. The initial dose of Oxybutynin ER will be 10 milligram (mg) and will be titrated to a maximum of 30 mg. Dosage will be adjusted in 5-mg increments at approximately 14-day intervals until continence is achieved or the participant cannot tolerate side effects. The duration of participation in the study will be 12 weeks. The study will consist of 6 visits: baseline, Weeks 2, 4, 6, 8 and 12. Week 4 and Week 8 will be telephone visits. Overall safety and efficacy of Oxybutinin ER will be assessed as well as safety and efficacy during the titration and maintenance phases. The efficacy of treatment will be assessed using urodynamic parameters (the force and flow of urine) and clinical parameters (voiding diary and catheterization [use or insertion of a tubular device to drain the bladder] schedules). The quality of life will also be monitored in the study.

Official Title
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Extended-Release Oxybutynin in the Treatment of Neurogenic Detrusor Overactivity (RONDO)

Conditions
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Detrusor Function, Overactive

Intervention / Treatment
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* Drug: Oxybutinin Extended-Release


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of overactive bladder as a result of neurogenic condition, for example following spinal cord injury, multiple sclerosis (slowly worsening disorder of the central nervous system that causes symptoms such as weakness, incoordination, numbness, problems talking and problems seeing), Parkinson's disease (a progressive disorder of the central nervous system, seen usually in older persons, in which there is slow movement [due to muscle weakness], trembling and sweating), or cerebrovascular accidents (CVAs - stroke-sudden loss of blood supply to brain) Women must not be pregnant and be of either non-childbearing potential or is using adequate means of birth control Overactive bladder symptoms and/or has urge incontinence episodes Must have normal results on urine culture tests and on urinalysis ECOG (Eastern Cooperative Oncology Group) performance status score of less than or equal to 3 Exclusion Criteria: Participants with 1 or more treatable or conditions, other than neurogenic bladder dysfunction, that may cause urinary incontinence or urgency Any medical or unstable condition that precludes their participation in the study or may confound the outcome of the study (participants with or at risk for urinary retention, gastric retention or uncontrolled narrow angle; heart failure or kidney failure; diabetes mellitus; abnormal muscle weakness [myasthenia gravis]; paralysis or inactivity in the intestines that prevents material moving through the gut [intestinal atony or paralytic ileus]; severe inflammation of the bowel [ulcerative colitis] sudden expansion of the large intestine seen in advanced ulcerative colitis or Crohn's disease [toxic megacolon]; history of major lower urinary tract surgery [transurethral resection will be excluded]) Hypersensitivity to the investigational drug or any of its ingredients (eg, lactose) Pregnant or breast feeding female Significant bacteriuria (presence of bacteria in the urine) or pyuria (presence of white blood cells) in the urine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxybutynin Extended-Release<br>Oxybutynin chloride 5, 10, 15 milligram (mg) per tablet 10-30 mg per day orally | Drug: Oxybutinin Extended-Release<br>* Oxybutynin chloride 5, 10, 15 milligram (mg) per tablet 10-30 mg per day orally<br>* Other names: Lyrinel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Detrusor Pressure | Maximal detrusor pressure represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. Detrusor pressure is the component of intravesical (in the bladder) pressure that is created by forces in the bladder wall (passive and active). It was estimated by subtracting abdominal pressure from intravesical pressure. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Cystometric Capacity (MCC) | MCC represents the maximum volume of urine the bladder holds. | Baseline and Week 12 | 
| Detrusor Leakpoint Pressure | Detrusor leakpoint pressure is the level of pressure at which leakage of urine through the urethra occurs as the bladder fills without an increase in abdominal pressure. This was a measure of both strength of the urethral sphincters and compliance of the detrusor muscle. | Baseline and Week 12 | 
| Post-Void Residual Urine Volume | Post-void residual urine volume is the amount of urine remaining in the bladder after void completion. | Baseline and Week 12 | 
| Reflex Volume | Reflex volume is the infused volume that induces the first detrusor contraction. | Baseline and Week 12 | 
| Urge Incontinence Episodes | Urge incontinence episodes were reported. Urge urinary incontinence is the complaint of involuntary leakage accompanied by or immediately preceded by urgency with sudden feeling to go to toilet. | Baseline, Week 4 and Week 12 | 
| Total Incontinence Episodes | Episodes of total urinary incontinence were reported. Urinary incontinence is the complaint of any involuntary leakage of urine. | Baseline, Week 4 and Week 12 | 
| Percentage of Participants With no Episodes of Urge-Urinary Incontinence | Percentage of participants with no episodes of urge urinary incontinence was reported. Urge urinary incontinence is the complaint of involuntary leakage accompanied by or immediately preceded by urgency. | Baseline, Week 4 and Week 12 | 
| King Health Questionnaire Score | King Health Questionnaire assesses the physical and psycho-social aspects of the disease state. It is a self-administered questionnaire containing 21 questions scored in 9 domains (general health perception, incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep or energy, and severity of urinary symptoms). All domains were assessed in a range: 0-100, where 0=best outcome/response and 100=worst outcome or response. Lower scores indicates better outcome or response. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Detrusor function, overactive, Urinary incontinence, Oxybutynin, Lyrinel