Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Neurogenic Overactive Bladder
Sponsor
Allergan (Industry)
Overall Status
Completed
CT.gov ID
NCT00461292
Collaborator
(none)
275
12
4
35
22.9
0.7
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety and effectiveness of botulinum toxin type A in treating overactive bladder in spinal cord injury or multiple sclerosis patients
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
275 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Study Start Date
:
May 1, 2007
Actual Primary Completion Date
:
Mar 1, 2010
Actual Study Completion Date
:
Apr 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 botulinum toxin Type A (200U) |
Biological: botulinum toxin Type A (200U)
botulinum toxin Type A 200 U injection at Day 1 followed by botulinum toxin Type A 200 U injection > Week 12; injections into detrusor
Other Names:
|
| Experimental: 2 botulinum toxin Type A (300U) |
Biological: botulinum toxin Type A (300U)
botulinum toxin Type A 300 U injection on Day 1 followed by botulinum toxin Type A 300 U injection > Week 12; injections into detrusor
Other Names:
|
| Other: 3 placebo; botulinum toxin Type A (200U) |
Other: Normal saline (Placebo); botulinum toxin Type A (200U)
Placebo injection on Day 1 followed by botulinum toxin Type A 200 U injection > 12 weeks; injections into detrusor
Other Names:
|
| Other: 4 placebo; botulinum toxin Type A (300U) |
Other: Normal saline (Placebo); botulinum toxin Type A (300U)
Placebo injection on Day 1 followed by botulinum toxin Type A 300 U injection > Week 12; injections into detrusor
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Number of Weekly Episodes of Urinary Incontinence [Baseline, Week 6]
Change from baseline in the weekly frequency of incontinence episodes at Week 6 after the first treatment. Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).
Secondary Outcome Measures
- Change From Baseline in Maximum Cystometric Capacity (MCC) [Baseline, Week 6]
Change from baseline in MCC at Week 6. MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in maximum volume of urine the bladder holds.
- Change From Baseline in Maximum Detrusor Pressure (MDP) [Baseline, Week 6]
Change from baseline in MDP during the first involuntary detrusor contraction at week 6. MDP represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. The greater the negative number change from baseline, the better the improvement.
- Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire [Baseline, Week 6]
Change from baseline in I-QOL questionnaire total score at Week 6, as completed by the patient. The I-QOL is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure 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). A positive change from baseline represents an improvement.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Exclusion Criteria:
-
History or evidence of pelvic or urologic abnormality
-
Previous or current diagnosis of bladder or prostate cancer
-
Urinary tract infection at time of enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Middlebury | Connecticut | United States | ||
| 2 | Rio de Janeiro | Brazil | |||
| 3 | Victoria | British Columbia | Canada | ||
| 4 | Salouel | France | |||
| 5 | Milan | Italy | |||
| 6 | Amsterdam | Netherlands | |||
| 7 | Porto | Portugal | |||
| 8 | Singapore | Singapore | |||
| 9 | Pretoria | South Africa | |||
| 10 | Tenerife | Spain | |||
| 11 | Hualien | Taiwan | |||
| 12 | Scunthorpe | United Kingdom |
Sponsors and Collaborators
- Allergan
Investigators
- Study Director: Medical Director, Allergan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Allergan
ClinicalTrials.gov Identifier:
NCT00461292
Other Study ID Numbers:
- 191622-516
First Posted:
Apr 17, 2007
Last Update Posted:
Oct 2, 2015
Last Verified:
Sep 1, 2015
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo |
|---|---|---|---|
| Arm/Group Description | botulinum toxin Type A (300U) | botulinum toxin Type A (200U) | Normal saline (placebo) |
| Period Title: Treatment Cycle 1 | |||
| STARTED | 91 | 92 | 92 |
| COMPLETED | 76 | 80 | 81 |
| NOT COMPLETED | 15 | 12 | 11 |
| Period Title: Treatment Cycle 1 | |||
| STARTED | 63 | 74 | 0 |
| COMPLETED | 58 | 72 | 0 |
| NOT COMPLETED | 5 | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | botulinum toxin Type A (300U) | botulinum toxin Type A (200U) | Normal saline (placebo) | Total of all reporting groups |
| Overall Participants | 91 | 92 | 92 | 275 |
| Age, Customized (participants) [Number] | ||||
| < 40 years |
30
33%
|
31
33.7%
|
25
27.2%
|
86
31.3%
|
| Between 40 and 64 years |
56
61.5%
|
55
59.8%
|
61
66.3%
|
172
62.5%
|
| Between 65 and 74 years |
4
4.4%
|
5
5.4%
|
5
5.4%
|
14
5.1%
|
| >= 75 years |
1
1.1%
|
1
1.1%
|
1
1.1%
|
3
1.1%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
52
57.1%
|
54
58.7%
|
49
53.3%
|
155
56.4%
|
| Male |
39
42.9%
|
38
41.3%
|
43
46.7%
|
120
43.6%
|
Outcome Measures
| Title | Change From Baseline in Number of Weekly Episodes of Urinary Incontinence |
|---|---|
| Description | Change from baseline in the weekly frequency of incontinence episodes at Week 6 after the first treatment. Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. A negative number change from baseline indicates a reduction in incontinence episodes (improvement). |
| Time Frame | Baseline, Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat, defined as all patients who started the study (randomized) |
| Arm/Group Title | Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo |
|---|---|---|---|
| Arm/Group Description | botulinum toxin Type A (300U) | botulinum toxin Type A (200U) | Normal saline (placebo) |
| Measure Participants | 91 | 92 | 92 |
| Baseline |
31.2
(18.14)
|
32.5
(18.44)
|
36.7
(30.67)
|
| Week 6 |
-19.4
(25.67)
|
-21.8
(18.06)
|
-13.2
(20.02)
|
| Title | Change From Baseline in Maximum Cystometric Capacity (MCC) |
|---|---|
| Description | Change from baseline in MCC at Week 6. MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in maximum volume of urine the bladder holds. |
| Time Frame | Baseline, Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat, defined as all patients who started the study (randomized) |
| Arm/Group Title | Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo |
|---|---|---|---|
| Arm/Group Description | botulinum toxin Type A (300U) | botulinum toxin Type A (200U) | Normal saline (placebo) |
| Measure Participants | 91 | 92 | 92 |
| Baseline |
246.8
(149.06)
|
247.3
(147.61)
|
249.4
(139.29)
|
| Week 6 |
157.2
(185.18)
|
157.0
(164.75)
|
6.5
(144.77)
|
| Title | Change From Baseline in Maximum Detrusor Pressure (MDP) |
|---|---|
| Description | Change from baseline in MDP during the first involuntary detrusor contraction at week 6. MDP represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. The greater the negative number change from baseline, the better the improvement. |
| Time Frame | Baseline, Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat, defined as all patients who started the study (randomized) |
| Arm/Group Title | Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo |
|---|---|---|---|
| Arm/Group Description | botulinum toxin Type A (300U) | botulinum toxin Type A (200U) | Normal saline (placebo) |
| Measure Participants | 91 | 92 | 92 |
| Baseline |
42.1
(33.21)
|
51.7
(40.95)
|
41.5
(31.17)
|
| Week 6 |
-26.9
(33.17)
|
-28.5
(47.82)
|
6.4
(41.10)
|
| Title | Change From Baseline in Total Score on Incontinence Quality of Life (I-QOL) Questionnaire |
|---|---|
| Description | Change from baseline in I-QOL questionnaire total score at Week 6, as completed by the patient. The I-QOL is a validated, disease-specific quality of life (QOL) questionnaire containing 22 questions designed to measure 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). A positive change from baseline represents an improvement. |
| Time Frame | Baseline, Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-To-Treat, defined as all patients who started the study (randomized) |
| Arm/Group Title | Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo |
|---|---|---|---|
| Arm/Group Description | botulinum toxin Type A (300U) | botulinum toxin Type A (200U) | Normal saline (placebo) |
| Measure Participants | 91 | 92 | 92 |
| Baseline |
36.32
(18.685)
|
37.46
(20.109)
|
35.72
(18.656)
|
| Week 6 |
24.26
(28.981)
|
24.43
(25.372)
|
11.71
(20.163)
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The safety population was used to calculate the number of participants at risk for SAEs and AEs and is the total number of patients that were randomized AND treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1. | |||||
| Arm/Group Title | Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo | |||
| Arm/Group Description | botulinum toxin Type A (300U) | botulinum toxin Type A (200U) | Normal saline (placebo) | |||
All Cause Mortality |
||||||
| Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/89 (20.2%) | 17/91 (18.7%) | 23/90 (25.6%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Cardiac disorders | ||||||
| Myocardial infarction | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Acute myocardial infarction | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Coronary artery disease | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal Pain | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Diarrhoea | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 5/89 (5.6%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Septic shock | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Upper respiratory tract infection | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Bacteraemia | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Endocarditis enterococcal | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Extradural abscess | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Osteomyelitis | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Paronychia | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Pyelonephritis | 0/89 (0%) | 0/91 (0%) | 2/90 (2.2%) | |||
| Pneumonia | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Sepsis | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Urosepsis | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Injury, poisoning and procedural complications | ||||||
| Procedural pain | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Fall | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Ankle fracture | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Bursa injury | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Urethral injury | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Investigations | ||||||
| Urine cytology abnormal | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| International normalised ratio increased | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Failure to thrive | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Acidosis | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Muscular weakness | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Foot deformity | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Intervertebral disc protrusion | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Joint contracture | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Neoplasm malignant | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Ovarian cancer | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Nervous system disorders | ||||||
| Multiple sclerosis relapse | 0/89 (0%) | 2/91 (2.2%) | 3/90 (3.3%) | |||
| Psychiatric disorders | ||||||
| Suicidal ideation | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal failure acute | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Calculus bladder | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Calculus urinary | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Haematuria | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Renal impairment | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Respiratory failure | 0/89 (0%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Chronic obstructive pulmonary disease | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Decubitus ulcer | 1/89 (1.1%) | 1/91 (1.1%) | 0/90 (0%) | |||
| Skin ulcer | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Surgical and medical procedures | ||||||
| Abortion induced | 0/89 (0%) | 0/91 (0%) | 1/90 (1.1%) | |||
| Vascular disorders | ||||||
| Thrombosis | 1/89 (1.1%) | 0/91 (0%) | 0/90 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Botulinum Toxin Type A (300U) | Botulinum Toxin Type A (200U) | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 70/89 (78.7%) | 63/91 (69.2%) | 52/90 (57.8%) | |||
| Gastrointestinal disorders | ||||||
| Constipation | 6/89 (6.7%) | 5/91 (5.5%) | 2/90 (2.2%) | |||
| Diarrhoea | 6/89 (6.7%) | 3/91 (3.3%) | 6/90 (6.7%) | |||
| General disorders | ||||||
| Fatigue | 3/89 (3.4%) | 8/91 (8.8%) | 1/90 (1.1%) | |||
| Pyrexia | 1/89 (1.1%) | 6/91 (6.6%) | 3/90 (3.3%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 57/89 (64%) | 51/91 (56%) | 36/90 (40%) | |||
| Nasopharyngitis | 6/89 (6.7%) | 6/91 (6.6%) | 3/90 (3.3%) | |||
| Influenza | 1/89 (1.1%) | 5/91 (5.5%) | 0/90 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Muscle spasms | 6/89 (6.7%) | 4/91 (4.4%) | 1/90 (1.1%) | |||
| Muscular weakness | 4/89 (4.5%) | 6/91 (6.6%) | 1/90 (1.1%) | |||
| Pain in extremity | 2/89 (2.2%) | 5/91 (5.5%) | 3/90 (3.3%) | |||
| Arthralgia | 1/89 (1.1%) | 3/91 (3.3%) | 5/90 (5.6%) | |||
| Renal and urinary disorders | ||||||
| Urinary retention | 28/89 (31.5%) | 18/91 (19.8%) | 3/90 (3.3%) | |||
| Haematuria | 9/89 (10.1%) | 5/91 (5.5%) | 4/90 (4.4%) | |||
| Dysuria | 7/89 (7.9%) | 5/91 (5.5%) | 2/90 (2.2%) | |||
| Urinary incontinence | 1/89 (1.1%) | 5/91 (5.5%) | 2/90 (2.2%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | Allergan, Inc. |
| Phone | 714-246-4500 |
| clinicaltrials@allergan.com |
Responsible Party:
Allergan
ClinicalTrials.gov Identifier:
NCT00461292
Other Study ID Numbers:
- 191622-516
First Posted:
Apr 17, 2007
Last Update Posted:
Oct 2, 2015
Last Verified:
Sep 1, 2015