Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder

This study will assess the safety and efficacy of botulinum toxin Type A for the treatment of urinary incontinence overactive bladder in patients with a spinal cord injury or multiple sclerosis.

Study Overview

• Status: Terminated
• Conditions: Overactive Bladder
• Intervention / Treatment: Biological: botulinum toxin Type A; Drug: Normal Saline (Placebo)

Detailed Description

Botulinum toxin Type A 300U has been discontinued from the study after regulatory approval of botulinum toxin Type A 200U. Patients remaining in the study who were allocated to receive botulinum toxin Type A 300U at treatment 2 (and had not yet received it) will receive botulinum toxin Type A 200U instead.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada
• India
  • Chennai, India
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Urinary incontinence as a result of neurogenic overactive bladder due to spinal cord injury or multiple sclerosis
• Inadequate response to anticholinergic medication used to treat overactive bladder.
• Neurological respiratory impairment and abnormal pulmonary function test results

Exclusion Criteria:

• History or evidence of pelvic or urologic abnormality
• Previous or current diagnosis of bladder or prostate cancer
• Symptomatic or untreated urinary tract infection at time of enrollment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: botulinum toxin Type A 200U; Botulinum toxin Type A 200U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Biological: botulinum toxin Type A; Botulinum toxin Type A injection into the detrusor.; Other Names: BOTOX®; onabotulinumtoxinA
Experimental: botulinum toxin Type A 300U; Botulinum toxin Type A 300U injection into the detrusor on Day 1 followed by a repeat botulinum toxin Type A 300U injection after a minimum of 12 weeks (if applicable).	Biological: botulinum toxin Type A; Botulinum toxin Type A injection into the detrusor.; Other Names: BOTOX®; onabotulinumtoxinA
Other: Placebo/botulinum toxin Type A 200U; Placebo (Normal Saline) injection into the detrusor on Day 1 followed by a botulinum toxin Type A 200U injection after a minimum of 12 weeks (if applicable).	Biological: botulinum toxin Type A; Botulinum toxin Type A injection into the detrusor.; Other Names: BOTOX®; onabotulinumtoxinA; Drug: Normal Saline (Placebo); Placebo (Normal Saline) injection into the detrusor.
Other: Placebo/botulinum toxin Type A 300U; Placebo (Normal Saline) injection into the detrusor on Day 1 followed by a botulinum toxin Type A 300U injection (200U after discontinuation of 300U) after a minimum of 12 weeks (if applicable).	Biological: botulinum toxin Type A; Botulinum toxin Type A injection into the detrusor.; Other Names: BOTOX®; onabotulinumtoxinA; Drug: Normal Saline (Placebo); Placebo (Normal Saline) injection into the detrusor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Vital Capacity (FVC)	Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible, at Baseline and Week 6. A positive change from Baseline indicated improvement.	Baseline, Week 6
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)	Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FEV1, the maximum amount of air exhaled in one second, at Baseline and Week 6. The highest value at each time-point was recorded. A positive change from Baseline indicated improvement.	Baseline, Week 6
Change From Baseline in FEV1/FVC Ratio	The FEV1/FVC ratio was calculated by dividing the FEV1 value by the FVC value representing the portion (or ratio) of FVC exhaled in one second. A positive change from Baseline indicated improvement.	Baseline, Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Number of Urinary Incontinence Episodes	The number of urinary incontinence episodes or leakage occurring over the previous 3 days was recorded in the patient bladder diary at Baseline and prior to Week 6. A negative change from Baseline indicated improvement (less incontinence/leakage).	Baseline, Week 6
Change From Baseline in the Maximum (Amplitude) Detrusor Pressure (MDP)	MDP was measured at the first involuntary detrusor contraction using urodynamic testing. A catheter was inserted into the bladder at Baseline and Week 6 and the pressure [measured in centimeters water (cm H20)] was determined as the bladder filled. A negative change from Baseline indicated improvement (less Detrusor pressure).	Baseline, Week 6
Change From Baseline in Maximum Cystometric Capacity (MCC)	MCC (the maximum amount of urine the bladder could hold) was measured using urodynamic testing. The amount of urine collected was subtracted from the total volume infused measured as milliliters (mL) of urine. A positive change from Baseline indicated improvement (fuller bladder/ less incontinence).	Baseline, Week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least a 15% Decrease From Baseline in FVC	Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible at Baseline, Weeks 2, 6 and 12.	Baseline, Weeks 2, 6 and 12
Number of Participants With at Least a 20% Decrease From Baseline in FVC	Spirometry was conducted according to American Thoracic Society standards. A spirometer was used to measure FVC, the maximum amount of air exhaled from the lungs after taking the deepest breath possible at Baseline, Weeks 2, 6 and 12.	Baseline, Weeks 2, 6 and 12

Collaborators and Investigators

• Sponsor: Allergan

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: February 21, 2007
• First Submitted That Met QC Criteria: February 21, 2007
• First Posted (Estimate): February 23, 2007

Study Record Updates

• Last Update Posted (Estimate): January 24, 2014
• Last Update Submitted That Met QC Criteria: December 9, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 191622-082