Overactive Bladder, Urinary Incontinence
Conditions
Brief summary
The purpose of this study is to provide confirmatory evidence of the safety and efficacy of two Dysport® (AbobotulinumtoxinA) doses (600 units \[U\] and 800 U), compared to placebo in reducing urinary incontinence (UI) in adult subjects treated for neurogenic detrusor overactivity (NDO) due to spinal cord injury (SCI) or multiple sclerosis (MS).
Interventions
BIOLOGICALBotulinum toxin type A
600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points
DRUGPlacebo
AbobotulinumtoxinA Placebo 600 U intra detrusor injection in two treatment periods (Initial and Retreatment phase) delivered at 30 injection points
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Urinary Incontinence for at least 3 months prior to Screening as a result of Neurogenic Detrusor Overactivity due to Spinal Cord Injury or Multiple Sclerosis. * Subjects with Spinal Cord Injury must have a stable neurological injury at T1 level or below which occurred at least 6 months prior to Screening. * Subjects with Multiple Sclerosis must be clinically stable in the investigator's opinion, with no exacerbation (relapse) of MS for at least 3 months prior to Screening. * Subjects must have had an inadequate response after at least 4 weeks of oral medications used in the treatment of NDO (e.g. anticholinergics, beta-3 agonists) and/or have intolerable side-effects. * Routinely performing Clean Intermittent Catheterization (CIC) to ensure adequate bladder emptying. * An average of at least two episodes per day of Urinary Incontinence recorded on the screening bladder diary. Key
Exclusion criteria
* Any current condition (other than NDO) that may impact on bladder function. * Previous or current, tumour or malignancy affecting the spinal column or spinal cord, or any other unstable cause of SCI. * Any condition that will prevent cystoscopic treatment administration or CIC usage, e.g. urethral strictures. * Current indwelling bladder catheter, or removal of indwelling bladder catheter less than 4 weeks prior to Screening. * BTX-A treatment within 9 months prior to Screening for any urological condition (e.g. detrusor or urethral sphincter treatments). * Any neuromodulation/electrostimulation usage for urinary symptoms/incontinence within 4 weeks prior to Screening. Any implanted neuromodulation device must be switched off at least 4 weeks prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle | Baseline and Week 6 of DBPC Cycle | The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The least square (LS) mean of the change in weekly number of UI episodes at 6 weeks after the first study treatment was calculated using a mixed model repeated measures (MMRM) analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at Week 6 of DBPC Cycle | Baseline and Week 6 of DBPC Cycle | All subjects had a standardised urodynamic filling cystometry assessment at baseline (screening) and again at Week 6 to determine the MDP. The LS mean of the change in MDP at 6 weeks after the first study treatment was calculated using an ANCOVA. |
| Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle | Baseline and Week 6 of DBPC Cycle | All subjects had a standardised urodynamic (filling cystometry) assessment at baseline (screening) and again at Week 6 to determine the Vol@1stIDC which is the instilled volume when first IDC commences. Subjects who did not exhibit a post-treatment IDC at Week 6 had Vol@1stIDC imputed using the recorded corrected MCC volume at Week 6. The LS mean of the change in Vol@1stIDC at 6 weeks after the first study treatment was calculated using an ANCOVA. |
| Number of Subjects With No Episodes of UI at Week 6 of DBPC Cycle | Baseline and Week 6 of DBPC Cycle | The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of subjects with no UI episodes at 6 weeks after the first study treatment was recorded and the percentage of subjects was also calculated from the total number of subjects with any number of UI events at Week 6. |
| Number of Subjects With No IDCs During Storage at Week 6 of DBPC Cycle | Baseline and Week 6 of DBPC Cycle | All subjects had a standardised urodynamic filling cystometry assessment at baseline (screening) and again at Week 6 to determine the occurrence of IDCs. The number of subjects without IDCs at 6 weeks after the first study treatment was recorded and the percentage of subjects was also calculated from the total number of subjects with data available for analysis at Week 6. |
| Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle | Baseline and Week 6 of DBPC Cycle | All subjects had a standardised urodynamic (filling cystometry) assessment at baseline (screening) and again at Week 6 to determine the MCC. The LS mean of the change in MCC at 6 weeks after the first study treatment was calculated using an analysis of covariance (ANCOVA). |
| Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | Baseline and Week 6 of DBPC Cycle | The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of baseline UI episodes was compared with the number of UI episodes at Week 6 to determine the level of response each subject reached, i.e. a decrease of ≥30%, ≥50% or ≥75% . The number of subjects showing an improvement of ≥30%, ≥50% and ≥75% were recorded and the percentage of subjects was also calculated from the total number of subjects with any number of UI events at Week 6. |
| Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle | Baseline and Week 6 of DBPC Cycle | The volume per void was measured during one 24-hour period of the 7-day bladder diary. The LS mean of the change in volume per void at 6 weeks after the first study treatment was calculated using a MMRM analysis. |
| Median Time Between Treatments | Day of first treatment (baseline) and day of retreatment, up to 2 years | Duration of effect for time between treatments was calculated by: (the date of the first retreatment visit - date of first treatment administration in the DBPC cycle). The median number of days between treatments was determined based on the Kaplan-Meier method. Subjects with no retreatment were censored at the last visit. |
| Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC Cycle | Baseline and Week 6 of DBPC Cycle | The I-QoL questionnaire is a validated, disease-specific questionnaire designed to measure the effect of UI on subjects' QoL. It consists of 22 items in 3 domains (avoidance and limiting behaviour, psychosocial impact and social embarrassment). Subjects used a 5-point response scale for each of the 22 items with values ranging from 1 (extremely) to 5 (not at all). The total summary score was transformed to a 100 point scale ranging from 0 to 100, with higher scores indicating a better QoL. The LS mean of the change in the I-QoL total summary score at 6 weeks after the first study treatment was calculated using a MMRM analysis. |
Countries
Canada, Czechia, Italy, Netherlands, Poland, Portugal, Romania, South Korea, Turkey (Türkiye), United States
Participant flow
Recruitment details
A total of 227 subjects with urinary incontinence (UI) caused by neurogenic detrusor overactivity (NDO) due to spinal cord injury (SCI) or multiple sclerosis (MS) were randomised at 64 study sites worldwide. One randomised subject was not eligible for entry and did not receive treatment. Hence, 226 subjects were randomised and treated during the study. The study was terminated early by the sponsor due to lack of recruitment.
Pre-assignment details
Subjects were randomised to 1 of 4 sequences: A) placebo in a double blind placebo controlled (DBPC) cycle then Dysport® 600 Units (U) in subsequent double blind cycles: B) placebo in DBPC cycle then Dysport® 800 U in subsequent cycles: C) Dysport® 600 U in all cycles: D) Dysport® 800 U in all cycles. The minimum re-treatment interval was 12 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects were administered placebo on Day 1 of the DBPC cycle. All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each.
Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required. | 76 |
| Dysport® 600 U Subjects were administered Dysport® 600 U for the first study treatment administration on Day 1 of the DBPC cycle.
All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each.
Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required. | 75 |
| Dysport® 800 U Subjects were administered Dysport® 800 U for the first study treatment administration on Day 1 of the DBPC cycle.
All study treatments were injected into the detrusor muscle via cystoscopy in a total volume of 15 mL divided into 30 injection points of 0.5 mL each.
Subjects were followed-up by telephone at Week 1 and Week 4; and attended clinic visits at Week 2, Week 6 (primary study timepoint), and Week 12. Thereafter telephone visits were scheduled every 12 weeks until end of study, or until retreatment was required. | 75 |
| Total | 226 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 | 2 |
| Overall Study | Lack of Efficacy | 1 | 2 | 1 |
| Overall Study | Lost to Follow-up | 4 | 4 | 1 |
| Overall Study | Not treated | 0 | 1 | 0 |
| Overall Study | Other | 1 | 1 | 0 |
| Overall Study | Sponsor Decision to Terminate Study | 57 | 57 | 62 |
| Overall Study | Withdrawal by Subject | 7 | 6 | 6 |
Baseline characteristics
| Characteristic | Placebo | Dysport® 600 U | Dysport® 800 U | Total |
|---|---|---|---|---|
| Aetiology of NDO MS | 25 Participants | 26 Participants | 27 Participants | 78 Participants |
| Aetiology of NDO SCI | 51 Participants | 49 Participants | 48 Participants | 148 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 4 Participants | 9 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 68 Participants | 71 Participants | 66 Participants | 205 Participants |
| Age, Continuous | 45.9 years STANDARD_DEVIATION 13.15 | 43.0 years STANDARD_DEVIATION 12.38 | 46.8 years STANDARD_DEVIATION 13.58 | 45.3 years STANDARD_DEVIATION 13.09 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 65 Participants | 70 Participants | 64 Participants | 199 Participants |
| Sex: Female, Male Female | 38 Participants | 27 Participants | 30 Participants | 95 Participants |
| Sex: Female, Male Male | 38 Participants | 48 Participants | 45 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 73 | 0 / 77 |
| other Total, other adverse events | 23 / 76 | 20 / 73 | 23 / 77 |
| serious Total, serious adverse events | 8 / 76 | 9 / 73 | 6 / 77 |
Outcome results
Primary
Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle
The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The least square (LS) mean of the change in weekly number of UI episodes at 6 weeks after the first study treatment was calculated using a mixed model repeated measures (MMRM) analysis.
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle | -12.7 Weekly UI episodes | Standard Error 2.01 |
| Dysport® 600 U | Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle | -23.5 Weekly UI episodes | Standard Error 2.04 |
| Dysport® 800 U | Mean Change From Baseline in Weekly Number of UI Episodes at Week 6 of DBPC Cycle | -24.9 Weekly UI episodes | Standard Error 1.97 |
Comparison: Treatment group, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[Botulinum toxin \[BTX\]-naïve or BTX-non-naïve\]) and study baseline value (weekly number of UI episodes) as fixed effect variables, and subject as a random effect.p-value: 0.000195% CI: [-16.36, -5.31]MMRM
Comparison: Treatment group, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and study baseline value (weekly number of UI episodes) as fixed effect variables, and subject as a random effect.p-value: <0.000195% CI: [-17.65, -6.73]MMRM
Secondary
Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC Cycle
The I-QoL questionnaire is a validated, disease-specific questionnaire designed to measure the effect of UI on subjects' QoL. It consists of 22 items in 3 domains (avoidance and limiting behaviour, psychosocial impact and social embarrassment). Subjects used a 5-point response scale for each of the 22 items with values ranging from 1 (extremely) to 5 (not at all). The total summary score was transformed to a 100 point scale ranging from 0 to 100, with higher scores indicating a better QoL. The LS mean of the change in the I-QoL total summary score at 6 weeks after the first study treatment was calculated using a MMRM analysis.
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC Cycle | 5.8 score on a scale | Standard Error 2.52 |
| Dysport® 600 U | Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC Cycle | 19.1 score on a scale | Standard Error 2.63 |
| Dysport® 800 U | Mean Change From Baseline in Incontinence Quality of Life (I-QoL) Questionnaire Total Summary Score at Week 6 of DBPC Cycle | 23.0 score on a scale | Standard Error 2.51 |
Comparison: Treatment group, visit (Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and study baseline value (I-QoL summary total score) as fixed variables, and subject as a random effect.p-value: 0.000395% CI: [6.22, 20.37]MMRM
Comparison: Treatment group, visit (Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and study baseline value (I-QoL summary total score) as fixed variables, and subject as a random effect.p-value: <0.000195% CI: [10.36, 24.15]MMRM
Secondary
Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle
All subjects had a standardised urodynamic (filling cystometry) assessment at baseline (screening) and again at Week 6 to determine the MCC. The LS mean of the change in MCC at 6 weeks after the first study treatment was calculated using an analysis of covariance (ANCOVA).
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle | -8.5 mL | Standard Error 18.06 |
| Dysport® 600 U | Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle | 152.4 mL | Standard Error 19.1 |
| Dysport® 800 U | Mean Change From Baseline in Maximum Cystometric Capacity (MCC) at Week 6 of DBPC Cycle | 180.7 mL | Standard Error 17.7 |
Comparison: Treatment group, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and baseline value of MCC as covariates.p-value: <0.000195% CI: [109.9, 211.9]ANCOVA
Comparison: Treatment group, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and baseline value of MCC as covariates.p-value: <0.000195% CI: [140.1, 238.2]ANCOVA
Secondary
Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at Week 6 of DBPC Cycle
All subjects had a standardised urodynamic filling cystometry assessment at baseline (screening) and again at Week 6 to determine the MDP. The LS mean of the change in MDP at 6 weeks after the first study treatment was calculated using an ANCOVA.
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at Week 6 of DBPC Cycle | -5.4 centimetres of water | Standard Error 2.83 |
| Dysport® 600 U | Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at Week 6 of DBPC Cycle | -29.8 centimetres of water | Standard Error 2.96 |
| Dysport® 800 U | Mean Change From Baseline in Maximum Detrusor Pressure (MDP) at Week 6 of DBPC Cycle | -34.1 centimetres of water | Standard Error 2.71 |
Comparison: Treatment group, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and baseline value of MDP as covariates.p-value: <0.000195% CI: [-32.3, -16.4]ANCOVA
Comparison: Treatment group, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and baseline value of MDP as covariates.p-value: <0.000195% CI: [-36.2, -21.1]ANCOVA
Secondary
Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle
All subjects had a standardised urodynamic (filling cystometry) assessment at baseline (screening) and again at Week 6 to determine the Vol@1stIDC which is the instilled volume when first IDC commences. Subjects who did not exhibit a post-treatment IDC at Week 6 had Vol@1stIDC imputed using the recorded corrected MCC volume at Week 6. The LS mean of the change in Vol@1stIDC at 6 weeks after the first study treatment was calculated using an ANCOVA.
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle | 14.0 mL | Standard Error 19.45 |
| Dysport® 600 U | Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle | 169.4 mL | Standard Error 20.72 |
| Dysport® 800 U | Mean Change From Baseline in Volume at First Involuntary Detrusor Contraction (Vol@1stIDC) at Week 6 of DBPC Cycle | 195.7 mL | Standard Error 19.12 |
Comparison: Treatment group, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and baseline value of Vol@1stIDC as covariates.p-value: <0.000195% CI: [100.5, 210.4]ANCOVA
Comparison: Treatment group, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and baseline value of Vol@1stIDC as covariates.p-value: <0.000195% CI: [129.2, 234.3]ANCOVA
Secondary
Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle
The volume per void was measured during one 24-hour period of the 7-day bladder diary. The LS mean of the change in volume per void at 6 weeks after the first study treatment was calculated using a MMRM analysis.
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle | 2.3 mL | Standard Error 14.92 |
| Dysport® 600 U | Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle | 87.1 mL | Standard Error 15.1 |
| Dysport® 800 U | Mean Change From Baseline in Volume Per Void at Week 6 of DBPC Cycle | 112.8 mL | Standard Error 14.5 |
Comparison: Treatment group, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and study baseline value (total volume per void) as fixed effect variables, and subject as a random effect.p-value: <0.000195% CI: [43.73, 125.89]MMRM
Comparison: Treatment group, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, recorded stratification factors (aetiology of NDO \[SCI or MS\], prior intradetrusor \[BTX-naïve or BTX-non-naïve\]) and study baseline value (total volume per void) as fixed effect variables, and subject as a random effect.p-value: <0.000195% CI: [70.17, 150.98]MMRM
Secondary
Median Time Between Treatments
Duration of effect for time between treatments was calculated by: (the date of the first retreatment visit - date of first treatment administration in the DBPC cycle). The median number of days between treatments was determined based on the Kaplan-Meier method. Subjects with no retreatment were censored at the last visit.
Time frame: Day of first treatment (baseline) and day of retreatment, up to 2 years
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Median Time Between Treatments | 120.5 days |
| Dysport® 600 U | Median Time Between Treatments | 215.0 days |
| Dysport® 800 U | Median Time Between Treatments | 224.0 days |
Secondary
Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle
The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of baseline UI episodes was compared with the number of UI episodes at Week 6 to determine the level of response each subject reached, i.e. a decrease of ≥30%, ≥50% or ≥75% . The number of subjects showing an improvement of ≥30%, ≥50% and ≥75% were recorded and the percentage of subjects was also calculated from the total number of subjects with any number of UI events at Week 6.
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment . Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥50% Improvement | 19 Participants |
| Placebo | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥30% Improvement | 32 Participants |
| Placebo | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥75% Improvement | 9 Participants |
| Dysport® 600 U | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥50% Improvement | 47 Participants |
| Dysport® 600 U | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥30% Improvement | 50 Participants |
| Dysport® 600 U | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥75% Improvement | 39 Participants |
| Dysport® 800 U | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥30% Improvement | 52 Participants |
| Dysport® 800 U | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥75% Improvement | 44 Participants |
| Dysport® 800 U | Number of Subjects With a UI Response at Improvement Levels ≥30%, ≥50%, and ≥75% at Week 6 of the DBPC Cycle | ≥50% Improvement | 50 Participants |
Comparison: Treatment comparison at ≥30% Improvement Level: Dysport® 600 U versus Placebo.p-value: 0.000795% CI: [1.8, 8.86]GLMM
Comparison: Treatment comparison at ≥30% Improvement Level: Dysport® 800 U versus Placebop-value: 0.001295% CI: [1.68, 7.86]GLMM
Comparison: Treatment comparison at ≥50% Improvement Level: Dysport® 600 U versus Placebo.p-value: <0.000195% CI: [3.56, 18.09]GLMM
Comparison: Treatment comparison at ≥50% Improvement Level: Dysport® 800 U versus Placebop-value: <0.000195% CI: [3.66, 18.47]GLMM
Comparison: Treatment comparison at ≥75% Improvement Level: Dysport® 600 U versus Placebo.p-value: <0.000195% CI: [4.59, 24.95]GLMM
Comparison: Treatment comparison at ≥75% Improvement Level: Dysport® 800 U versus Placebo.p-value: <0.000195% CI: [5.4, 29.56]GLMM
Secondary
Number of Subjects With No Episodes of UI at Week 6 of DBPC Cycle
The weekly number of UI episodes was measured using a 7-day bladder diary. Bladder diaries that contained data recorded on at least 5 days were included in the analysis. The number of subjects with no UI episodes at 6 weeks after the first study treatment was recorded and the percentage of subjects was also calculated from the total number of subjects with any number of UI events at Week 6.
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment . Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Subjects With No Episodes of UI at Week 6 of DBPC Cycle | 3 Participants |
| Dysport® 600 U | Number of Subjects With No Episodes of UI at Week 6 of DBPC Cycle | 21 Participants |
| Dysport® 800 U | Number of Subjects With No Episodes of UI at Week 6 of DBPC Cycle | 21 Participants |
Comparison: Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.p-value: 0.000695% CI: [2.72, 35.6]Generalised linear mixed model (GLMM)
Comparison: Treatment group, recorded stratification factors, visit (Week 2, Week 6 and Week 12), treatment-by-visit interaction, study baseline-by-visit interaction and study baseline weekly number of UI episodes as fixed effect.p-value: 0.000395% CI: [3.05, 39.61]GLMM
Secondary
Number of Subjects With No IDCs During Storage at Week 6 of DBPC Cycle
All subjects had a standardised urodynamic filling cystometry assessment at baseline (screening) and again at Week 6 to determine the occurrence of IDCs. The number of subjects without IDCs at 6 weeks after the first study treatment was recorded and the percentage of subjects was also calculated from the total number of subjects with data available for analysis at Week 6.
Time frame: Baseline and Week 6 of DBPC Cycle
Population: mITT population: All randomised subjects who received at least 1 administration of study treatment. Subjects were analysed as randomised (planned treatment). Only subjects with data available for analysis at Week 6 of DBPC cycle are presented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Subjects With No IDCs During Storage at Week 6 of DBPC Cycle | 6 Participants |
| Dysport® 600 U | Number of Subjects With No IDCs During Storage at Week 6 of DBPC Cycle | 20 Participants |
| Dysport® 800 U | Number of Subjects With No IDCs During Storage at Week 6 of DBPC Cycle | 42 Participants |
Comparison: Treatment group, and recorded stratification factors (aetiology of NDO, previous BTX-A usage) and study baseline (prior intradetrusor BTX-A usage for UI) as explanatory variables.p-value: 0.00195% CI: [2.02, 16.24]Regression, Logistic
Comparison: Treatment group, and recorded stratification factors (aetiology of NDO, previous BTX-A usage) and study baseline (prior intradetrusor BTX-A usage for UI) as explanatory variables.p-value: <0.000195% CI: [5.82, 44.43]Regression, Logistic