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Safety and Efficacy Study of OnabotulinumtoxinA for the Treatment of Urinary Incontinence Due to Neurogenic Detrusor Overactivity (NDO) in Non-Catheterizing Patients With Multiple Sclerosis (MS)

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ClinicalTrials.gov Identifier: NCT01600716
Recruitment Status : Completed
First Posted : May 17, 2012
Results First Posted : March 22, 2016
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
Allergan

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Urinary Incontinence
Multiple Sclerosis
Neurogenic Bladder
Interventions Biological: OnabotulinumtoxinA
Drug: Placebo (Normal Saline)
Enrollment 144
Recruitment Details  
Pre-assignment Details  
Arm/Group Title OnabotulinumtoxinA Placebo (Normal Saline)
Hide Arm/Group Description OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection. Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Period Title: Overall Study
Started 66 78
Completed 59 71
Not Completed 7 7
Reason Not Completed
Other Reasons             3             1
Personal Reasons             0             2
Lost to Follow-up             0             2
Pregnancy             1             0
Lack of Efficacy             2             1
Adverse Event             1             1
Arm/Group Title OnabotulinumtoxinA Placebo (Normal Saline) Total
Hide Arm/Group Description OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection. Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection. Total of all reporting groups
Overall Number of Baseline Participants 66 78 144
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 78 participants 144 participants
<65 years
62
  93.9%
71
  91.0%
133
  92.4%
≥65 years
4
   6.1%
7
   9.0%
11
   7.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 78 participants 144 participants
Female
57
  86.4%
70
  89.7%
127
  88.2%
Male
9
  13.6%
8
  10.3%
17
  11.8%
1.Primary Outcome
Title Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes
Hide Description Incontinence is defined as involuntary loss of urine as recorded in a patient bladder diary. The number of episodes of urinary incontinence is recorded over a 3-day period the week of the study visit. A negative number change from baseline indicates a reduction in incontinence episodes (improvement) and a positive number change indicates an increase in incontinence episodes (worsening).
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population: all randomized patients
Arm/Group Title OnabotulinumtoxinA Placebo (Normal Saline)
Hide Arm/Group Description:
OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.
Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Overall Number of Participants Analyzed 66 78
Mean (Standard Deviation)
Unit of Measure: Episodes
Baseline 4.18  (3.167) 4.32  (2.422)
Change from Baseline at Week 6 -3.34  (2.881) -1.10  (2.083)
2.Secondary Outcome
Title Change From Baseline in Maximum Cystometric Capacity (MCC)
Hide Description MCC represents the maximum volume of urine the bladder holds. A positive number change from baseline represents an improvement (increase) in the maximum volume of urine the bladder holds and a negative number change from baseline represents a worsening (decrease) in the maximum volume of urine the bladder holds.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population: all randomized patients with data at the time points
Arm/Group Title OnabotulinumtoxinA Placebo (Normal Saline)
Hide Arm/Group Description:
OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.
Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Overall Number of Participants Analyzed 65 78
Mean (Standard Deviation)
Unit of Measure: Milliliters (mL)
Baseline 246.4  (138.49) 245.7  (133.90)
Change from Baseline at Week 6 (N=62,72) 127.2  (139.25) -1.8  (93.23)
3.Secondary Outcome
Title Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC)
Hide Description Maximum detrusor pressure represents the maximum pressure (peak amplitude) in the bladder during the first involuntary contraction of the bladder muscle. A negative number change from baseline indicates an improvement in pressure and a positive number change from baseline indicates a worsening in pressure.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population: all randomized patients with data at the time points
Arm/Group Title OnabotulinumtoxinA Placebo (Normal Saline)
Hide Arm/Group Description:
OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.
Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Overall Number of Participants Analyzed 57 69
Mean (Standard Deviation)
Unit of Measure: Centimeters of Water (cm H2O)
Baseline 35.9  (34.90) 36.1  (37.21)
Change from Baseline at Week 6 (N=25,51) -19.6  (37.61) 3.7  (33.24)
4.Secondary Outcome
Title Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score
Hide Description 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 and a negative change from baseline represents a worsening.
Time Frame Baseline, Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population: all randomized patients with data at the time points
Arm/Group Title OnabotulinumtoxinA Placebo (Normal Saline)
Hide Arm/Group Description:
OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.
Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Overall Number of Participants Analyzed 58 74
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
Baseline 32.43  (16.337) 34.24  (21.163)
Change from Baseline at Week 6 (N=55,68) 40.39  (26.499) 9.92  (15.863)
5.Other Pre-specified Outcome
Title Duration of Treatment Effect Through Week 52
Hide Description The duration of treatment effect is the time to patient request for retreatment.
Time Frame Up to 52 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population: all randomized patients
Arm/Group Title OnabotulinumtoxinA Placebo (Normal Saline)
Hide Arm/Group Description:
OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for a second onabotulinumtoxinA injection.
Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, patients could request/qualify for an onabotulinumtoxinA injection.
Overall Number of Participants Analyzed 66 78
Median (95% Confidence Interval)
Unit of Measure: Weeks
51.7 [1] 
(36.9 to NA)
12.6
(12.3 to 13.0)
[1]
The upper confidence limit was not estimable since too few patients had requested retreatment prior to the end of the study.
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events and serious adverse events are analyzed by treatment cycle (cycle 1 and cycle 2).
 
Arm/Group Title OnabotulinumtoxinA Treatment Cycle 1 Placebo (Normal Saline) OnabotulinumtoxinA/OnabotulinumtoxinA Treatment Cycle 2 Placebo (Normal Saline)/OnabotulinumtoxinA
Hide Arm/Group Description OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. Median duration of exposure is 50.7 weeks. Placebo (normal saline) is administered into the detrusor at Day 1. Median duration of exposure is 15.2 weeks. OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1. After a minimum of 12 weeks, a second onabotulinumtoxinA injection is given. Median duration of exposure is 12.5 weeks. Placebo (normal saline) is administered into the detrusor at Day 1. After a minimum of 12 weeks, an onabotulinumtoxinA injection is given. Median duration of exposure is 12.2 weeks.
All-Cause Mortality
OnabotulinumtoxinA Treatment Cycle 1 Placebo (Normal Saline) OnabotulinumtoxinA/OnabotulinumtoxinA Treatment Cycle 2 Placebo (Normal Saline)/OnabotulinumtoxinA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
OnabotulinumtoxinA Treatment Cycle 1 Placebo (Normal Saline) OnabotulinumtoxinA/OnabotulinumtoxinA Treatment Cycle 2 Placebo (Normal Saline)/OnabotulinumtoxinA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/66 (10.61%)   3/78 (3.85%)   0/30 (0.00%)   2/67 (2.99%) 
Cardiac disorders         
Acute Coronary Syndrome  1  1/66 (1.52%)  0/78 (0.00%)  0/30 (0.00%)  0/67 (0.00%) 
General disorders         
Pyrexia * 1  1/66 (1.52%)  0/78 (0.00%)  0/30 (0.00%)  0/67 (0.00%) 
Infections and infestations         
Urinary Tract Infection  1  3/66 (4.55%)  0/78 (0.00%)  0/30 (0.00%)  0/67 (0.00%) 
Infectious Colitis  1  0/66 (0.00%)  1/78 (1.28%)  0/30 (0.00%)  0/67 (0.00%) 
Injury, poisoning and procedural complications         
Spinal Compression Fracture  1  1/66 (1.52%)  1/78 (1.28%)  0/30 (0.00%)  0/67 (0.00%) 
Fall * 1  1/66 (1.52%)  0/78 (0.00%)  0/30 (0.00%)  1/67 (1.49%) 
Musculoskeletal and connective tissue disorders         
Muscular Weakness * 1 [1]  1/66 (1.52%)  0/78 (0.00%)  0/30 (0.00%)  0/67 (0.00%) 
Nervous system disorders         
Multiple Sclerosis Relapse * 1  0/66 (0.00%)  1/78 (1.28%)  0/30 (0.00%)  0/67 (0.00%) 
Multiple sclerosis  1  0/66 (0.00%)  0/78 (0.00%)  0/30 (0.00%)  1/67 (1.49%) 
Renal and urinary disorders         
Dysuria * 1  1/66 (1.52%)  0/78 (0.00%)  0/30 (0.00%)  0/67 (0.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 17.1
[1]
Onset date was 135 days after administration of onabotulinumtoxinA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
OnabotulinumtoxinA Treatment Cycle 1 Placebo (Normal Saline) OnabotulinumtoxinA/OnabotulinumtoxinA Treatment Cycle 2 Placebo (Normal Saline)/OnabotulinumtoxinA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   50/66 (75.76%)   44/78 (56.41%)   21/30 (70.00%)   38/67 (56.72%) 
Gastrointestinal disorders         
Diarrhoea * 1  1/66 (1.52%)  4/78 (5.13%)  1/30 (3.33%)  0/67 (0.00%) 
Infections and infestations         
Urinary tract infection  1  26/66 (39.39%)  9/78 (11.54%)  9/30 (30.00%)  17/67 (25.37%) 
Bacteriuria  1  12/66 (18.18%)  6/78 (7.69%)  3/30 (10.00%)  6/67 (8.96%) 
Nasopharyngitis * 1  4/66 (6.06%)  1/78 (1.28%)  0/30 (0.00%)  0/67 (0.00%) 
Investigations         
Residual Urine Volume  1  11/66 (16.67%)  2/78 (2.56%)  1/30 (3.33%)  5/67 (7.46%) 
Nervous system disorders         
Multiple Sclerosis Relapse  1  0/66 (0.00%)  2/78 (2.56%)  2/30 (6.67%)  0/67 (0.00%) 
Psychiatric disorders         
Insomnia * 1  0/66 (0.00%)  1/78 (1.28%)  2/30 (6.67%)  0/67 (0.00%) 
Renal and urinary disorders         
Urinary Retention * 1  11/66 (16.67%)  3/78 (3.85%)  6/30 (20.00%)  9/67 (13.43%) 
Leukocyturia  1  4/66 (6.06%)  6/78 (7.69%)  1/30 (3.33%)  2/67 (2.99%) 
Dysuria  1  6/66 (9.09%)  1/78 (1.28%)  3/30 (10.00%)  1/67 (1.49%) 
Haematuria  1  3/66 (4.55%)  6/78 (7.69%)  0/30 (0.00%)  2/67 (2.99%) 
Renal Cyst  1  3/66 (4.55%)  3/78 (3.85%)  3/30 (10.00%)  1/67 (1.49%) 
Micturition Urgency * 1  2/66 (3.03%)  0/78 (0.00%)  2/30 (6.67%)  0/67 (0.00%) 
Pollakiuria * 1  2/66 (3.03%)  0/78 (0.00%)  2/30 (6.67%)  0/67 (0.00%) 
Urine Abnormality  1  1/66 (1.52%)  0/78 (0.00%)  2/30 (6.67%)  0/67 (0.00%) 
Urine Odour Abnormal * 1  1/66 (1.52%)  0/78 (0.00%)  2/30 (6.67%)  0/67 (0.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head,
Organization: Allergan, Inc
Phone: 714-246-4500
EMail: clinicaltrials@allergan.com
Layout table for additonal information
Responsible Party: Allergan
ClinicalTrials.gov Identifier: NCT01600716    
Other Study ID Numbers: 191622-117
First Submitted: May 15, 2012
First Posted: May 17, 2012
Results First Submitted: February 17, 2016
Results First Posted: March 22, 2016
Last Update Posted: April 30, 2019