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

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

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:

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: Botox; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male outpatients of any race, between 40 and 90 years of age.
2. Clinical signs and symptoms of frequency (>=8 micturitions/day) and urgency (>=2 episodes/day).
3. 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.
4. OAB inadequately controlled with anticholinergic medications, as per Investigator opinion.
5. Qmax >12mL/s with a voided volume of >125mL.
6. IPSS >12, with IPSS QoL >3 at study Visit 1.
7. Willing to use clean intermittent catheterization (CIC) to empty the bladder or is willing to have an indwelling catheter, if necessary following study treatment.
8. Able to understand the requirements of the study, including completing questionnaires and signing Informed Consent/HIPAA.

Exclusion Criteria:

1. 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.
2. Known history of clinically significant cardiovascular disease, cerebrovascular disease, or arrhythmia.
3. History of spinal cord injury or multiple sclerosis, or other neurological disease which may be contributing to OAB.
4. Known history of hydronephrosis.
5. Current indwelling catheter, or removal of chronic catheter <1 month prior to study entry.
6. Non-compliance with wash-out periods for prohibited medications/therapies (Supplement I).
7. Evidence of Urinary Tract Infection according to local standard of care.
8. Serum PSA of >10ng/mL.
9. 24 hour total volume voided >3000 mL of urine. [As determined by completion of a patient bladder diary during the screening period]
10. 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.
11. Allergy or sensitivity to any component of BOTOX® (Section 5.2).
12. Known uncontrolled systemic disease.
13. Evidence of recent alcohol/drug abuse.
14. 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.
15. History of poor cooperation, non-compliance with medical treatment, or unreliability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Botox; 200U onabotulinumtoxinA (botox)	Drug: Botox; Botox injection
Placebo Comparator: Placebo; 200U Saline	Drug: Placebo; Placebo injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Alexis Te, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): November 13, 2012

Study Registration Dates

• First Submitted: June 22, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 14, 2010

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 7, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: OAB
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive
• Other Study ID Numbers: BTX0621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided