A Long-term Follow-up Study of Botulinum Toxin Type A in Patients With Overactive Bladder as a Result of Spinal Injury or Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT00876447
• Recruitment Status: Completed
• First Posted: April 6, 2009
• Results First Posted: June 13, 2014
• Last Update Posted: May 1, 2019
• Sponsor: Allergan
• Information provided by (Responsible Party): Allergan

Study Description

Brief Summary:

The purpose of this study is to assess the long-term safety and effectiveness of botulinum toxin type A on patients with overactive bladder as a result of spinal cord injury or multiple sclerosis. This is a follow-up study to two Allergan sponsored studies (NCT00311376 and NCT00461292).

Condition or disease	Intervention/treatment	Phase
Overactive Bladder	Biological: Botulinum Toxin Type A 300U; Biological: Botulinum Toxin Type A 200U	Phase 3

Detailed Description:

Botulinum toxin Type A 300U has been discontinued from the study. Patients remaining in the arm containing botulinum toxin Type A 300U will receive botulinum toxin Type A 200U moving forward. Also, the masking of the study is now open-label.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 397 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: January 1, 2009
• Actual Primary Completion Date: June 12, 2013
• Actual Study Completion Date: September 4, 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Botulinum Toxin Type A 300U; Botulinum toxin Type A 300U injections into the detrusor > 12 weeks as needed for up to 3 years.	Biological: Botulinum Toxin Type A 300U; Botulinum toxin Type A 300U injections into the detrusor > 12 weeks as needed for up to 3 years.; Other Name: BOTOX®
Experimental: Botulinum Toxin Type A 200U; Botulinum toxin Type A 200U injections into the detrusor > 12 weeks as needed for up to 3 years.	Biological: Botulinum Toxin Type A 200U; Botulinum toxin Type A 200U injections into the detrusor > 12 weeks as needed for up to 3 years.; Other Name: BOTOX®

Outcome Measures

Primary Outcome Measures :

1. Change From Study Baseline in the Daily Average Number of Urinary Incontinence Episodes [ Time Frame: Study Baseline, Week 6 Treatment Cycle 1 ]
   Urinary incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary in the 3 consecutive days prior to each study visit for study 191622-094 (or 7 days prior to each visit in study 191622-515 or 191622-516). The number of incontinence episodes are averaged daily during this period. The initial study baseline is obtained from the patient bladder diary in the 7 consecutive days prior to the first treatment in either study 191622-515 or 191622-516. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).
2. Change From Study Baseline in the Daily Average Number of Urinary Incontinence Episodes [ Time Frame: Study Baseline, Week 6 Treatment Cycle 2 ]
   Urinary incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary in the 3 consecutive days prior to each study visit for study 191622-094 (or 7 days prior to each visit in study 191622-515 or 191622-516). The number of incontinence episodes are averaged daily during this period. The initial study baseline is obtained from the patient bladder diary in the 7 consecutive days prior to the first treatment in either study 191622-515 or 191622-516. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).
3. Change From Study Baseline in the Daily Average Number of Urinary Incontinence Episodes [ Time Frame: Study Baseline, Week 6 Treatment Cycle 3 ]
   Urinary incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary in the 3 consecutive days prior to each study visit for study 191622-094 (or 7 days prior to each visit in study 191622-515 or 191622-516). The number of incontinence episodes are averaged daily during this period. The initial study baseline is obtained from the patient bladder diary in the 7 consecutive days prior to the first treatment in either study 191622-515 or 191622-516. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).
4. Change From Study Baseline in the Daily Average Number of Urinary Incontinence Episodes [ Time Frame: Study Baseline, Week 6 Treatment Cycle 4 ]
   Urinary incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary in the 3 consecutive days prior to each study visit for study 191622-094 (or 7 days prior to each visit in study 191622-515 or 191622-516). The number of incontinence episodes are averaged daily during this period. The initial study baseline is obtained from the patient bladder diary in the 7 consecutive days prior to the first treatment in either study 191622-515 or 191622-516. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).
5. Change From Study Baseline in the Daily Average Number of Urinary Incontinence Episodes [ Time Frame: Study Baseline, Week 6 Treatment Cycle 5 ]
   Urinary incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary in the 3 consecutive days prior to each study visit for study 191622-094 (or 7 days prior to each visit in study 191622-515 or 191622-516). The number of incontinence episodes are averaged daily during this period. The initial study baseline is obtained from the patient bladder diary in the 7 consecutive days prior to the first treatment in either study 191622-515 or 191622-516. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).

Secondary Outcome Measures :

1. Change From Study Baseline in the Incontinence Quality of Life Instrument (I-QOL) Total Summary Score [ Time Frame: Study Baseline, Week 6 Treatment Cycle 1 ]
   The I-QOL questionnaire is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure the impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0 = worst QOL and 100= best QOL). The I-QOL total score is calculated by combining the 22-item subscores from the 3 I-QOL domains: Avoidance Limiting Behavior, Psychological Impact, and Social Embarrassment. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improved QOL.
2. Change From Study Baseline in the Incontinence Quality of Life Instrument (I-QOL) Total Summary Score [ Time Frame: Study Baseline, Week 6 Treatment Cycle 2 ]
   The I-QOL questionnaire is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure the impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0 = worst QOL and 100= best QOL). The I-QOL total score is calculated by combining the 22-item subscores from the 3 I-QOL domains: Avoidance Limiting Behavior, Psychological Impact, and Social Embarrassment. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improved QOL.
3. Change From Study Baseline in the Incontinence Quality of Life Instrument (I-QOL) Total Summary Score [ Time Frame: Study Baseline, Week 6 Treatment Cycle 3 ]
   The I-QOL questionnaire is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure the impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0 = worst QOL and 100= best QOL). The I-QOL total score is calculated by combining the 22-item subscores from the 3 I-QOL domains: Avoidance Limiting Behavior, Psychological Impact, and Social Embarrassment. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improved QOL.
4. Change From Study Baseline in the Incontinence Quality of Life Instrument (I-QOL) Total Summary Score [ Time Frame: Study Baseline, Week 6 Treatment Cycle 4 ]
   The I-QOL questionnaire is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure the impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0 = worst QOL and 100= best QOL). The I-QOL total score is calculated by combining the 22-item subscores from the 3 I-QOL domains: Avoidance Limiting Behavior, Psychological Impact, and Social Embarrassment. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improved QOL.
5. Change From Study Baseline in the Incontinence Quality of Life Instrument (I-QOL) Total Summary Score [ Time Frame: Study Baseline, Week 6 Treatment Cycle 5 ]
   The I-QOL questionnaire is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure the impact of urinary incontinence on patients' lives. Each question is answered on a 5-point scale (1 = worst QOL and 5 = best QOL). The scores are totaled over the 22 questions and normalized to a score of 0-100 (0 = worst QOL and 100= best QOL). The I-QOL total score is calculated by combining the 22-item subscores from the 3 I-QOL domains: Avoidance Limiting Behavior, Psychological Impact, and Social Embarrassment. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improved QOL.
6. Change From Study Baseline in Volume Per Void [ Time Frame: Study Baseline, Week 6 Treatment Cycle 1 ]
   The total volume voided (voluntary or by catheterization) is recorded by the patient over a 24-hour period preceding the study visit. The average volume per voiding episode is derived by dividing the total volume collected in a 24-hour period by the total number of urinary episodes with volume recorded in the same 24-hour period. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improvement.
7. Change From Study Baseline in Volume Per Void [ Time Frame: Study Baseline, Week 6 Treatment Cycle 2 ]
   The total volume voided (voluntary or by catheterization) is recorded by the patient over a 24-hour period preceding the study visit. The average volume per voiding episode is derived by dividing the total volume collected in a 24-hour period by the total number of urinary episodes with volume recorded in the same 24-hour period. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improvement.
8. Change From Study Baseline in Volume Per Void [ Time Frame: Study Baseline, Week 6 Treatment Cycle 3 ]
   The total volume voided (voluntary or by catheterization) is recorded by the patient over a 24-hour period preceding the study visit. The average volume per voiding episode is derived by dividing the total volume collected in a 24-hour period by the total number of urinary episodes with volume recorded in the same 24-hour period. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improvement.
9. Change From Study Baseline in Volume Per Void [ Time Frame: Study Baseline, Week 6 Treatment Cycle 4 ]
   The total volume voided (voluntary or by catheterization) is recorded by the patient over a 24-hour period preceding the study visit. The average volume per voiding episode is derived by dividing the total volume collected in a 24-hour period by the total number of urinary episodes with volume recorded in the same 24-hour period. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improvement.
10. Change From Study Baseline in Volume Per Void [ Time Frame: Study Baseline, Week 6 Treatment Cycle 5 ]
    The total volume voided (voluntary or by catheterization) is recorded by the patient over a 24-hour period preceding the study visit. The average volume per voiding episode is derived by dividing the total volume collected in a 24-hour period by the total number of urinary episodes with volume recorded in the same 24-hour period. The initial study baseline is obtained from data collected prior to the first treatment in Study 191622-515 or 191622-516. Positive number changes from baseline indicate improvement.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient has participated in study 191622-515 or 191622-516 and the following criteria fulfilled:

  • Patient completed at least 52 weeks in the preceding study.
  • No longer than 6 months has elapsed since completion of the preceding study
  • Patient has not received any prohibited medications during any intervening period between the preceding study and this long-term study.

Exclusion Criteria:

• History or evidence of pelvic or urologic abnormality.
• Previous or current diagnosis of bladder or prostate cancer.

Contacts and Locations

Locations

United States, Connecticut

Middlebury, Connecticut, United States

Australia

Randwick, Australia

Austria

Innsbruck, Austria

Belgium

Ghent, Belgium

Brazil

Rio de Janeiro, Brazil

Canada, British Columbia

Victoria, British Columbia, Canada

Czechia

Ostrava, Czechia

France

Salouel, France

Germany

Kiel, Germany

Italy

Florence, Italy

Netherlands

Amsterdam, Netherlands

New Zealand

Epsom, New Zealand

Poland

Poznan, Poland

Portugal

Porto, Portugal

Russian Federation

Moscow, Russian Federation

Singapore

Singapore, Singapore

Slovakia

Presov, Slovakia

South Africa

Pretoria, South Africa

Spain

Tenerife, Spain

Taiwan

Hualien, Taiwan

Ukraine

Kiev, Ukraine

United Kingdom

London, United Kingdom

Sponsors and Collaborators

Allergan

Investigators

• Study Director: Medical Director; Allergan

More Information

Publications:

Kennelly M, Dmochowski R, Schulte-Baukloh H, Ethans K, Del Popolo G, Moore C, Jenkins B, Guard S, Zheng Y, Karsenty G; 191622-094 Investigators. Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long-term extension study. Neurourol Urodyn. 2017 Feb;36(2):368-375. doi: 10.1002/nau.22934. Epub 2015 Nov 24.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT00876447
• Other Study ID Numbers: 191622-094
• First Posted: April 6, 2009
• Results First Posted: June 13, 2014
• Last Update Posted: May 1, 2019
• Last Verified: April 2019

Additional relevant MeSH terms:

Urinary Bladder, Overactive; Urinary Bladder Diseases; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents