Botox for the Treatment of Overactive Bladder Secondary to Benign Prostatic Obstruction

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blind study comparing intravesical injection of BOTOX to placebo. Study subjects will be randomized (1:1 ratio) to one of the following treatment groups:

Detailed Description
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Group 1 n=20 BOTOX® 200U Group 2 n=20 Placebo BOTOX® (saline) At Visit 2 (Treatment, Day 0), subjects will receive one injection cycle of BOTOX (200U) or placebo (saline). The study duration is approximately 284 days and consists of a Screening Visit (Day -7 to -14), a Treatment/Randomization Visit (Visit 2, Day 0), and Follow-up Visits at 7, 30, 90, 180, and 270 Days. Telephone Follow-ups will be made 3 days following the injection cycle. Subjects demonstrating an insufficient response to treatment may receive an open-label injection cycle of BOTOX (200U) at Day 90. Subjects receiving this injection will re-commence Follow-up Visits and be followed for an additional 270 days.

Official Title
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Randomized Double-blind Placebo Controlled Trial of Intradetrusor Injections of Botox for the Treatment of Refractory Overactive Bladder Secondary to Benign Prostatic Obstruction-BTX0621

Conditions
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Overactive Bladder

Intervention / Treatment
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* Drug: Botox
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male outpatients of any race, between 40 and 90 years of age. Clinical signs and symptoms of frequency (>=8 micturitions/day) and urgency (>=2 episodes/day). Urodynamic history consistent with OAB that developed in conjunction with BPO and that persists for at least 3 months post TURP or PVP, RRP or other obstruction relieving procedure. OAB inadequately controlled with anticholinergic medications, as per Investigator opinion. Qmax >12mL/s with a voided volume of >125mL. IPSS >12, with IPSS QoL >3 at study Visit 1. Willing to use clean intermittent catheterization (CIC) to empty the bladder or is willing to have an indwelling catheter, if necessary following study treatment. Able to understand the requirements of the study, including completing questionnaires and signing Informed Consent/HIPAA. Exclusion Criteria: Known history of interstitial cystitis, uninvestigated hematuria, bladder outlet obstruction due to vesical neck contracture, mullerian duct cysts, urethral obstruction due to stricture/valves/sclerosis of urethral tumor, radiation cystitis, genitourinary tuberculosis, bladder calculi, or detrusor-sphincter dyssynergia. Known history of clinically significant cardiovascular disease, cerebrovascular disease, or arrhythmia. History of spinal cord injury or multiple sclerosis, or other neurological disease which may be contributing to OAB. Known history of hydronephrosis. Current indwelling catheter, or removal of chronic catheter <1 month prior to study entry. Non-compliance with wash-out periods for prohibited medications/therapies (Supplement I). Evidence of Urinary Tract Infection according to local standard of care. Serum PSA of >10ng/mL. 24 hour total volume voided >3000 mL of urine. [As determined by completion of a patient bladder diary during the screening period] Medical condition that may increase their risk of exposure to botulinum toxin including diagnosed Myasthenia Gravis, Eaton-Lambert Syndrome, Amyotrophic Lateral Sclerosis or any other disease that might interfere with neuromuscular function. Allergy or sensitivity to any component of BOTOX® (Section 5.2). Known uncontrolled systemic disease. Evidence of recent alcohol/drug abuse. Subjects who, in the opinion of the Investigator, have a significant condition that puts them at significant risk, may confound study results, or interfere with study participation. History of poor cooperation, non-compliance with medical treatment, or unreliability.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Botox<br>200U onabotulinumtoxinA (botox) | Drug: Botox<br>* Botox injection<br>|
| Placebo Comparator: Placebo<br>200U Saline | Drug: Placebo<br>* Placebo injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Frequency | This is the measure of urinary frequency at baseline for those in the placebo and botox arms to day 270 | From Baseline to Day 270 | 
| Urgency | This measured the degree of urinary urgency using a 3-day voiding diary. Patients were assessed for the number of urgency episodes they had by answering yes or no. | From Baseline to Day 270 | 
| Quality of Life (QoL) | Quality of Life (QoL) is from the ICIQ-QAB (international Consultation of Incontinence Overactive Bladder) Questionnaire. It is scored 25-160 and those with higher scores have higher impact on quality of life. | From Baseline to Day 270 | 
| International Consultation on Incontinence Questionnaire (ICIQ) | ICIQ is a brief validated instrument that is comprehensive for the assessment of incontinence and measures frequency, severity and impact on quality of life. There are a total of 23 items. The overall score ranges from 1-84 with greater values indicating increased symptom severity. Bother scales are not incorporated in the overall score but indicate impact of individual symptoms for the patient. | From Baseline to Day 270 | 
| Postvoid Residual Volume (PVR) | Postvoid residual volume (PVR) is the volume of fluid remaining in the bladder immediately after the completion of micturition. | From Baseline to Day 270 | 
| Maximum Flow Rate (Qmax) | Qmax is the the maximum recorded flow rate | From Baseline to Day 270 | 
| International Prostate Symptom Score (IPSS) | International Prostate Symptom Score (IPSS) -is a 7 point scale used to screen, track and manage symptoms associated with BPH. The symptoms questions include feeling of incomplete bladder emptying, frequency, intermittency, urgency, weak stream, straining and nocturia. Scores range from 1 to 5 for a total of maximum 35 points (0-7 Mildly symptomatic, 8-19 Moderately symptomatic, 20-35 Severely symptomatic) | From Baseline to Day 270 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OAB