Multiple Sclerosis, Neurogenic Bladder, Urinary Incontinence
Conditions
Brief summary
This study will evaluate the safety and efficacy of OnabotulinumtoxinA (BOTOX®) for the treatment of urinary incontinence due to NDO in non-catheterizing patients with MS.
Interventions
BIOLOGICALOnabotulinumtoxinA
OnabotulinumtoxinA 100 U is administered into the detrusor at Day 1 in the onabotulinumtoxinA 100 U arm. After a minimum of 12 weeks, patients in both the onabotulinumtoxinA 100 U arm and the placebo arm could request/qualify for an onabotulinumtoxinA injection.
DRUGPlacebo (Normal Saline)
Placebo (normal saline) is administered into the detrusor at Day 1.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 3 episodes of urinary incontinence over a 3-day period * History of Multiple Sclerosis (MS) * Urinary incontinence not adequately controlled by anticholinergic medication
Exclusion criteria
* Current use of intermittent catheter or indwelling catheter to manage urinary incontinence * Previous or current botulinum toxin therapy of any serotype for any urological condition * Previous or current botulinum toxin therapy of any serotype for any non-urological condition within the last 12 weeks * Diagnosis of myasthenia gravis, Eaton-Lambert Syndrome, or Amyotrophic Lateral Sclerosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes | Baseline, Week 6 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline, Week 6 | 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. |
| Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) | Baseline, Week 6 | 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. |
| Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score | Baseline, Week 6 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of Treatment Effect Through Week 52 | Up to 52 Weeks | The duration of treatment effect is the time to patient request for retreatment. |
Countries
Belgium, Canada, Czechia, France, Poland, Portugal, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OnabotulinumtoxinA 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. | 66 |
| Placebo (Normal Saline) 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. | 78 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lack of Efficacy | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Other Reasons | 3 | 1 |
| Overall Study | Personal Reasons | 0 | 2 |
| Overall Study | Pregnancy | 1 | 0 |
Baseline characteristics
| Characteristic | OnabotulinumtoxinA | Placebo (Normal Saline) | Total |
|---|---|---|---|
| Age, Customized <65 years | 62 Participants | 71 Participants | 133 Participants |
| Age, Customized ≥65 years | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Female | 57 Participants | 70 Participants | 127 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 50 / 66 | 44 / 78 | 21 / 30 | 38 / 67 |
| serious Total, serious adverse events | 7 / 66 | 3 / 78 | 0 / 30 | 2 / 67 |
Outcome results
Primary
Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes
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
Population: Intent-to-Treat Population: all randomized patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes | Baseline | 4.18 Episodes | Standard Deviation 3.167 |
| OnabotulinumtoxinA | Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes | Change from Baseline at Week 6 | -3.34 Episodes | Standard Deviation 2.881 |
| Placebo (Normal Saline) | Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes | Baseline | 4.32 Episodes | Standard Deviation 2.422 |
| Placebo (Normal Saline) | Change From Baseline in Daily Average Frequency of Urinary Incontinence Episodes | Change from Baseline at Week 6 | -1.10 Episodes | Standard Deviation 2.083 |
Secondary
Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score
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
Population: Intent-to-Treat Population: all randomized patients with data at the time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score | Baseline | 32.43 Scores on a Scale | Standard Deviation 16.337 |
| OnabotulinumtoxinA | Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score | Change from Baseline at Week 6 (N=55,68) | 40.39 Scores on a Scale | Standard Deviation 26.499 |
| Placebo (Normal Saline) | Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score | Baseline | 34.24 Scores on a Scale | Standard Deviation 21.163 |
| Placebo (Normal Saline) | Change From Baseline in Incontinence Quality of Life Instrument (I-QOL) Total Summary Score | Change from Baseline at Week 6 (N=55,68) | 9.92 Scores on a Scale | Standard Deviation 15.863 |
Secondary
Change From Baseline in Maximum Cystometric Capacity (MCC)
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
Population: Intent-to-Treat Population: all randomized patients with data at the time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline | 246.4 Milliliters (mL) | Standard Deviation 138.49 |
| OnabotulinumtoxinA | Change From Baseline in Maximum Cystometric Capacity (MCC) | Change from Baseline at Week 6 (N=62,72) | 127.2 Milliliters (mL) | Standard Deviation 139.25 |
| Placebo (Normal Saline) | Change From Baseline in Maximum Cystometric Capacity (MCC) | Baseline | 245.7 Milliliters (mL) | Standard Deviation 133.9 |
| Placebo (Normal Saline) | Change From Baseline in Maximum Cystometric Capacity (MCC) | Change from Baseline at Week 6 (N=62,72) | -1.8 Milliliters (mL) | Standard Deviation 93.23 |
Secondary
Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC)
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
Population: Intent-to-Treat Population: all randomized patients with data at the time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OnabotulinumtoxinA | Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) | Baseline | 35.9 Centimeters of Water (cm H2O) | Standard Deviation 34.9 |
| OnabotulinumtoxinA | Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) | Change from Baseline at Week 6 (N=25,51) | -19.6 Centimeters of Water (cm H2O) | Standard Deviation 37.61 |
| Placebo (Normal Saline) | Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) | Baseline | 36.1 Centimeters of Water (cm H2O) | Standard Deviation 37.21 |
| Placebo (Normal Saline) | Change From Baseline in Maximum Detrusor Pressure During the First Involuntary Detrusor Contraction (IDC) | Change from Baseline at Week 6 (N=25,51) | 3.7 Centimeters of Water (cm H2O) | Standard Deviation 33.24 |
Other Pre-specified
Duration of Treatment Effect Through Week 52
The duration of treatment effect is the time to patient request for retreatment.
Time frame: Up to 52 Weeks
Population: Intent-to-Treat Population: all randomized patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| OnabotulinumtoxinA | Duration of Treatment Effect Through Week 52 | 51.7 Weeks |
| Placebo (Normal Saline) | Duration of Treatment Effect Through Week 52 | 12.6 Weeks |