Study of Botulinum Toxin Type A for the Treatment of Patients With Idiopathic Overactive Bladder With Urinary Incontinence

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00910845
• Collaborator: (none)
• Enrollment: 557
• Locations: 2
• Arms: 2
• Duration (Months): 21.9
• Patients Per Site: 278.5
• Patients Per Site Per Month: 12.7

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and effectiveness of botulinum toxin type A (onabotulinumtoxinA) in treating patients with idiopathic overactive bladder with urinary incontinence.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder	Biological: onabotulinumtoxinA; Drug: normal saline	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 557 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: onabotulinumtoxinA OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable).	Biological: onabotulinumtoxinA; OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable). Or, if placebo is administered at Day 1, onabotulinumtoxinA 100 U injected after a minimum of 12 weeks (if applicable).; Other Names: BOTOX® botulinum toxin Type A
Other: placebo/onabotulinumtoxinA Placebo (normal saline) injected into the detrusor at Day 1, followed by an injection of onabotulinumtoxinA (botulinum toxin Type A) 100 U after a minimum of 12 weeks (if applicable).	Biological: onabotulinumtoxinA; OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable). Or, if placebo is administered at Day 1, onabotulinumtoxinA 100 U injected after a minimum of 12 weeks (if applicable).; Other Names: BOTOX® botulinum toxin Type A ; Drug: normal saline; Normal saline (placebo) injected into the detrusor at Day 1.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Number of Daily Episodes of Urinary Incontinence [Baseline, Week 12]

   A urinary incontinence episode is defined as an incident of involuntary loss of urine as recorded in a patient bladder diary during the 3 days before the Baseline and Week 12 study visits. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).

Secondary Outcome Measures

1. Change From Baseline in Number of Daily Micturition Episodes [Baseline, Week 12]

   The number of micturition episodes (the number of times a patient urinates into the toilet) was recorded by the patient in a bladder diary during 3 consecutive days in the week prior to the Baseline and prior to the Week 12 study visit. A negative number change from baseline indicates a reduction in micturition episodes (improvement).

2. Change From Baseline in Volume Voided Per Micturition [Baseline, Week 12]

   The total volume voided was measured over one 24-hour period in the week prior to the Baseline and Week 12 study visit and recorded by the patient in the bladder diary. This was used to calculate volume voided per micturition. A positive number change from baseline indicates an increase in volume voided per micturition (improvement).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Symptoms of OAB (frequency/urgency) with urinary incontinence for at least 6 months

• Inadequate response or limiting side effects with anticholinergics for the treatment of OAB

Exclusion Criteria:

• Overactive Bladder caused by neurological condition

• Patient has predominance of stress incontinence

• History or evidence of pelvic or urological abnormality

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Newport Beach	California	United States
2		Victoria	British Columbia	Canada

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: NCT00910845
• Other Study ID Numbers: 191622-095
• First Posted: Jun 1, 2009
• Last Update Posted: Mar 5, 2013
• Last Verified: Jan 1, 2013

• Additional relevant MeSH terms: Urinary Bladder, Overactive; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA

Study Results

Participant Flow

Arm/Group Title	onabotulinumtoxinA	Placebo/onabotulinumtoxinA
Arm/Group Description	OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable).	Placebo (normal saline) injected into the detrusor at Day 1, followed by an injection of onabotulinumtoxinA (botulinum toxin Type A) 100 U after a minimum of 12 weeks (if applicable).
Period Title: Treatment Cycle 1
STARTED	280	277
COMPLETED	249	243
NOT COMPLETED	31	34
Period Title: Treatment Cycle 1
STARTED	141	212
COMPLETED	136	203
NOT COMPLETED	5	9

Baseline Characteristics

Arm/Group Title	onabotulinumtoxinA	Placebo/onabotulinumtoxinA	Total
Arm/Group Description	OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable).	Placebo (normal saline) injected into the detrusor at Day 1, followed by an injection of onabotulinumtoxinA (botulinum toxin Type A) 100 U after a minimum of 12 weeks (if applicable).	Total of all reporting groups
Overall Participants	280	277	557
Age, Customized (Number) [Number]
< 40 years	9 3.2%	17 6.1%	26 4.7%
Between 40 and 64 years	150 53.6%	143 51.6%	293 52.6%
Between 65 and 74 years	75 26.8%	73 26.4%	148 26.6%
≥ 75 years	46 16.4%	44 15.9%	90 16.2%
Sex: Female, Male (Count of Participants)
Female	252 90%	245 88.4%	497 89.2%
Male	28 10%	32 11.6%	60 10.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Number of Daily Episodes of Urinary Incontinence
Description	A urinary incontinence episode is defined as an incident of involuntary loss of urine as recorded in a patient bladder diary during the 3 days before the Baseline and Week 12 study visits. A negative number change from baseline indicates a reduction in incontinence episodes (improvement).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized patients.

Arm/Group Title	onabotulinumtoxinA	Placebo/onabotulinumtoxinA
Arm/Group Description	OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable).	Placebo (normal saline) injected into the detrusor at Day 1, followed by an injection of onabotulinumtoxinA (botulinum toxin Type A) 100 U after a minimum of 12 weeks (if applicable).
Measure Participants	280	277
Baseline	5.47 (3.621)	5.09 (3.204)
Change from Baseline at Week 12	-2.65 (3.333)	-0.87 (2.833)

2. Secondary Outcome

Title	Change From Baseline in Number of Daily Micturition Episodes
Description	The number of micturition episodes (the number of times a patient urinates into the toilet) was recorded by the patient in a bladder diary during 3 consecutive days in the week prior to the Baseline and prior to the Week 12 study visit. A negative number change from baseline indicates a reduction in micturition episodes (improvement).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized patients.

Arm/Group Title	onabotulinumtoxinA	Placebo/onabotulinumtoxinA
Arm/Group Description	OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable).	Placebo (normal saline) injected into the detrusor at Day 1, followed by an injection of onabotulinumtoxinA (botulinum toxin Type A) 100 U after a minimum of 12 weeks (if applicable).
Measure Participants	280	277
Baseline	11.98 (4.259)	11.20 (3.070)
Change from Baseline at Week 12	-2.15 (2.933)	-0.91 (2.577)

3. Secondary Outcome

Title	Change From Baseline in Volume Voided Per Micturition
Description	The total volume voided was measured over one 24-hour period in the week prior to the Baseline and Week 12 study visit and recorded by the patient in the bladder diary. This was used to calculate volume voided per micturition. A positive number change from baseline indicates an increase in volume voided per micturition (improvement).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intent-to-treat population included all randomized patients.

Arm/Group Title	onabotulinumtoxinA	Placebo/onabotulinumtoxinA
Arm/Group Description	OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable).	Placebo (normal saline) injected into the detrusor at Day 1, followed by an injection of onabotulinumtoxinA (botulinum toxin Type A) 100 U after a minimum of 12 weeks (if applicable).
Measure Participants	280	277
Baseline	156.4 (63.21)	161.1 (68.65)
Change from Baseline at Week 12	41.1 (87.58)	9.7 (59.02)

Adverse Events

Adverse Event Reporting Description	The safety population was used to calculate the number of participants at risk for Serious Adverse Events (SAEs) and Adverse Events (AEs) and is the total number of patients who were treated. S(AE)s are displayed for the placebo-controlled treatment Cycle 1.
Arm/Group Title	onabotulinumtoxinA		Placebo/onabotulinumtoxinA
Arm/Group Description	OnabotulinumtoxinA (botulinum toxin Type A) 100 U injected into the detrusor at Day 1, followed by a repeat injection of onabotulinumtoxinA 100 U after a minimum of 12 weeks (if applicable).		Placebo (normal saline) injected into the detrusor at Day 1, followed by an injection of onabotulinumtoxinA (botulinum toxin Type A) 100 U after a minimum of 12 weeks (if applicable).
All Cause Mortality
	onabotulinumtoxinA		Placebo/onabotulinumtoxinA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	onabotulinumtoxinA		Placebo/onabotulinumtoxinA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/278 (6.5%)		16/272 (5.9%)
Cardiac disorders
Coronary artery disease	1/278 (0.4%)		1/272 (0.4%)
Myocardial infarction	1/278 (0.4%)		0/272 (0%)
Angina pectoris	0/278 (0%)		1/272 (0.4%)
Congenital, familial and genetic disorders
Foramen magnum stenosis	1/278 (0.4%)		0/272 (0%)
Ear and labyrinth disorders
Vertigo	1/278 (0.4%)		0/272 (0%)
Gastrointestinal disorders
Colitis	1/278 (0.4%)		0/272 (0%)
Volvulus	1/278 (0.4%)		0/272 (0%)
Intestinal perforation	0/278 (0%)		1/272 (0.4%)
Infections and infestations
Pneumonia	2/278 (0.7%)		0/272 (0%)
Diverticulitis	1/278 (0.4%)		1/272 (0.4%)
Abscess limb	1/278 (0.4%)		0/272 (0%)
Appendiceal abscess	1/278 (0.4%)		0/272 (0%)
Folliculitis	1/278 (0.4%)		0/272 (0%)
Pneumocystis jiroveci pneumonia	1/278 (0.4%)		0/272 (0%)
Abscess	0/278 (0%)		1/272 (0.4%)
Injury, poisoning and procedural complications
Cervical vertebral fracture	1/278 (0.4%)		0/272 (0%)
Femur fracture	0/278 (0%)		1/272 (0.4%)
Procedural hypotension	0/278 (0%)		1/272 (0.4%)
Metabolism and nutrition disorders
Dehydration	1/278 (0.4%)		2/272 (0.7%)
Obesity	1/278 (0.4%)		1/272 (0.4%)
Electrolyte imbalance	0/278 (0%)		1/272 (0.4%)
Hypokalaemia	0/278 (0%)		1/272 (0.4%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/278 (0.4%)		3/272 (1.1%)
Arthritis	1/278 (0.4%)		1/272 (0.4%)
Spinal column stenosis	0/278 (0%)		1/272 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/278 (0%)		1/272 (0.4%)
Renal cell carcinoma	0/278 (0%)		1/272 (0.4%)
Psychiatric disorders
Depression	2/278 (0.7%)		0/272 (0%)
Bipolar disorder	1/278 (0.4%)		0/272 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/278 (0%)		1/272 (0.4%)
Pulmonary embolism	0/278 (0%)		1/272 (0.4%)
Pulmonary oedema	0/278 (0%)		1/272 (0.4%)
Other (Not Including Serious) Adverse Events
	onabotulinumtoxinA		Placebo/onabotulinumtoxinA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	155/278 (55.8%)		79/272 (29%)
Infections and infestations
Urinary tract infection	68/278 (24.5%)		25/272 (9.2%)
Bacteriuria	23/278 (8.3%)		10/272 (3.7%)
Renal and urinary disorders
Dysuria	40/278 (14.4%)		27/272 (9.9%)
Urinary retention	16/278 (5.8%)		1/272 (0.4%)
Haematuria	8/278 (2.9%)		16/272 (5.9%)

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.