Detrusor Overactivity, Overactive Bladder
Conditions
Keywords
Vesicare, Solifenacin, Detrusor Overactivity, Urinary Nerve Growth Factor, Overactive Bladder, Bladder wall thickness
Brief summary
The purpose is to see if solifenacin has any effect on bladder wall thickness and urine inflammatory marker measurements after 12 weeks of treatment.
Detailed description
Participants satisfying all selection criteria at the end of the 2-week, single blind, placebo run-in period were randomized to receive 12-week double-blind treatment with solifenacin 5 mg or 10 mg once daily, or placebo.
Interventions
DRUGPlacebo
Matching solifenacin placebo tablet
DRUGsolifenacin
Tablet for oral administration
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Symptoms of overactive bladder (OAB), including urinary frequency, urgency or urge incontinence, for greater than or equal to 3 months * Urodynamic diagnosis of detrusor overactivity (DO) * Either naïve to anti-muscarinic treatment (i.e. no prior history of use of anti-muscarinic agents) or 6-months anti-muscarinic treatment free (i.e. have had no anti-muscarinic treatment within 6 months) prior to the screening visit * Bladder post-void residual volume of less than 30 ml * Available to complete the study
Exclusion criteria
* History of stress urinary incontinence, urethral sphincter incompetence or neurogenic detrusor overactivity * History, signs or symptoms suggestive of urinary tract infection (confirmed by positive urine analysis), obstruction or urogenital pro-lapse (greater than grade II) * History of urinary tract operation within 6 months prior to screening * Indwelling catheter or permanent catheter fitted * History of pelvic area radiotherapy treatment * Uncontrolled diabetes mellitus * History of fibromyalgia * Post-partum or breast-feeding within 3 months prior to screening visit * Either pregnant or intends to become pregnant during the study or sexually active, of childbearing potential and is unwilling to utilize a reliable method of birth control (note: reliable methods are contraceptive pills of combination type, hormonal implants or injectable contraceptives) * Positive pre-study hepatitis B surface antigen, hepatitis C antibody or human immunodeficiency virus (HIV) result at time of screening * History of drug and / or alcohol abuse at time of screening * History of urinary retention, severe gastrointestinal obstruction (including paralytic ileus or intestinal atony or toxic megacolon or severe ulcerative colitis), myasthenia gravis, uncontrolled narrow angle glaucoma or shallow anterior chamber or deemed to be at risk for these conditions * Undergoing hemodialysis or has severe renal impairment or moderate hepatic impairment or who are on treatment with a potent cytochrome p450 (CYP) 3A4 inhibitor, e.g. Ketoconazole * Currently dosing with medication(s) intended to treat overactive bladder symptoms or has a history of non-drug treatment, such as electrical therapy, magnetic field stimulation, pelvic floor treatment or bladder training intended to treat overactive bladder symptoms within 6 months prior to screening, as described in the list of prohibited medications * Currently receiving or has a history of treatment with alpha blockers, botulinum toxin (cosmetic use is acceptable), resiniferatoxin or pelvic floor muscle relaxants within 9 months prior to screening * Participated in any clinical study less than or equal to 3 months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Bladder Wall Thickness | Baseline and Week 12 | Bladder wall thickness (BWT) measurements were obtained using transvaginal ultrasound. The BWT was derived as one mean value per image pooled over measurements of 3 locations (anterior wall, dome and trigone), and performed by 2 central readers and 1 adjudicator. |
| Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | Week 12 | Free (neutralized) urinary nerve growth factor (uNGF) and creatinine (Cr) were measured from urine samples by the central laboratories. Free (neutralized) uNGF/Cr was derived by dividing free (neutralized) uNGF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Baseline, Week 6 and Week 12 | Bladder wall thickness (BWT) measurements were obtained using transvaginal ultrasound. The BWT was derived as one mean value per image pooled over measurements of 3 locations (anterior wall, dome and trigone), and performed by 2 central readers and 1 adjudicator. |
| Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Baseline, Week 6 and Week 12 | Free (neutralized) urinary nerve growth factor (uNGF) and creatinine (Cr) were measured from urine samples by the central laboratories. Free (neutralized) uNGF/Cr was derived by dividing free (neutralized) uNGF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant. |
| Change From Baseline to Week 12 in Mean Number of Events (Micturitions Plus Incontinence Episodes) Per 24 Hours | Baseline and Week 12 | The average number of micturitions (urinations) and incontinence episodes (any involuntary leakage of urine) per day was derived from the number of events recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits. |
| Change From Baseline to Week 12 in Mean Number of Urgency Events Per 24 Hours | 12 weeks | The intensity of urgency of each micturition (urination) and incontinence episode (any involuntary leakage of urine) was recorded by the participant in an electronic diary according to the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. An urgency event is defined as any micturition or incontinence episode classified by the participant as a grade 3 or 4 on the PPIUS scale. The average number of urgency events per day is derived from the diary data completed by participants on the 3 days prior to the Baseline and Week 12 visits. |
| Change From Baseline to Week 12 in Mean Number of Micturitions Per 24 Hours | Baseline and Week 12 | The average number of micturitions (urinations) per 24 hours was derived from the number of micturitions recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits. |
| Change From Baseline to Week 12 in Mean Number of Urgency Micturitions Per 24 Hours | Baseline and Week 12 | An urgency micturition is defined as any micturition classified by the participant as a grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The average number of urgency micturitions per 24 hours was derived from the number of urgency micturitions recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits. |
| Change From Baseline to Week 12 in Mean Number of Incontinence Episodes Per 24 Hours | Baseline and Week 12 | The average number of incontinence episodes (any involuntary leakage of urine) per 24 hours was calculated from the number of incontinence episodes recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits. |
| Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 3 or 4 Per 24 Hours | Baseline and Week 12 | An urgency incontinence episode is defined as any incontinence episode classified by the participant as a grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The average number of grade 3 or 4 urgency incontinence episodes per 24 hours was calculated from the number of urgency incontinence episodes recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits. |
| Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 4 Per 24 Hours | Baseline and Week 12 | An urgency incontinence episode is defined as any incontinence episode classified by the participant as a grade 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The average number of grade 4 urgency incontinence episodes per 24 hours was calculated from the number of urgency incontinence episodes recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits. |
| Change From Baseline to Week 12 in Mean Level of Urgency | Baseline and Week 12 | The intensity of urgency of each micturition (urination) and incontinence episode (any involuntary leakage of urine) was recorded by the participant in an electronic diary according to the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The mean level of urgency was calculated by adding the PPIUS grade for all events (micturition or incontinence) and dividing by the number of episodes recorded in the diary over 3 days prior to the Baseline and Week 12 visits. |
| Total Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | Week 12 | Total (acidified) urinary nerve growth factor (uNGF) and creatinine (Cr) were measured from urine samples by the central laboratories. Total uNGF/Cr was derived by dividing total uNGF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant. |
| Change From Baseline in Patient Perception of Bladder Condition (PPBC) | Baseline and Week 12 | The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 1: 'Does not cause me any problems at all'; 2: 'Causes me some very minor problems'; 3: 'Causes me some minor problems'; 4: 'Causes me (some) moderate problems'; 5: 'Causes me severe problems' and 6: 'Causes me many severe problems'. A negative change from Baseline score indicates improvement. |
| Change From Baseline in Patient Assessment of Urgency Bother | Baseline and Week 12 | The participants' perception and impression of bother associated with their condition were assessed using the Urgency Bother-Visual Analog Scale (UB-VAS). The participant was asked to place a vertical mark on a 100 mm line to indicate how much bother has urgency been for them in the past week, whereby 'no bother at all' is represented on the left end (score = 0) and 'worst possible bother' (score = 100) at the right end of the line. A negative change from Baseline indicates improvement. |
| Change From Baseline in Patient Assessment of Treatment Satisfaction | Baseline and Week 12 | The treatment satisfaction visual analog scale (TS\_VAS) asks patients to rate their satisfaction with treatment by placing a vertical mark on a 100 mm line where the endpoints are labeled 'No, not at all' on the left (score = 0) to 'Yes, completely satisfied' on the right (score = 100). A positive change from Baseline indicates improvement. |
| Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Baseline and Week 12 | The participants' quality of life was assessed using the EuroQoL 5 Dimension Questionnaire (EQ-5D). The EQ-5D is a standardized instrument for use as a measure of health outcome and is based on the following 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. For each dimension participants were asked to select the statement which best described their health that day, from level 1 (indicating no problems) to 3 (indicating extreme problems/unable to perform). Improvement was defined as a change from a state of being unable to perform or extreme problems at Baseline to no problems or to some or moderate problems at Week 12, and from some or moderate problems to no problems. Worsening was defined as a change from no problems at Baseline to some or moderate problems or to a state of being unable to perform or extreme problems at Week 12, and from some or moderate problems to a state of being unable to perform or extreme problems. |
| Change From Baseline in EuroQoL 5-Dimension Questionnaire Visual Analog Scale | Baseline and Week 12 | The participants' quality of life was assessed using the EuroQoL 5 Dimension Questionnaire (EQ-5D) visual analog scale (VAS). Health status is completed by the participant indicating their own health state today by drawing a line on a vertical scale from 0 to 100 where the endpoints are labeled 'Worst imaginable health state' (=0) and 'Best imaginable health state' (=100). On the EQ-5D VAS, a positive change from Baseline indicates improvement. |
| Change From Baseline in Symptom Bother Score | Baseline and Week 12 | Overactive bladder symptoms were assessed using the symptom bother scale of the Overactive Bladder Symptom and Health-Related Quality of Life Questionnaire (OAB-q). The OAB-q is a patient-administered instrument comprising an 8-item symptom bother scale and 25 health-related quality of life items (see next outcome measure). In the symptom bother scale participants were asked how much they had been bothered by selected bladder symptoms during the past 4 weeks. Each question has a 6-point Likert scale response ranging from 'not at all' (1) to 'a very great deal' (6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from Baseline in symptom bother score indicates improvement. |
| Change From Baseline in Health-Related Quality of Life (HRQL) | Baseline and Week 12 | Health-related quality of life was assessed by the Overactive Bladder Symptom and Health-Related Quality of Life Questionnaire (OAB-q). The OAB-q is a patient-administered instrument comprising of an 8-item symptom bother scale (see previous outcome measure) and 25 HRQL items comprising 4 subscales (concern, coping, social interaction and sleep) and a total HRQL score. Participants were asked how their overall bladder symptoms had affected their life in the past 4 weeks. Each of the 25 HRQL questions has a 6-point Likert scale response ranging from 'none of the time' (1) to 'all of the time' (6). The HRQL subscale scores were calculated by summing the responses of the items within each subscale.The HRQL total score was calculated by adding the 4 HRQL subscale scores,. All scores were transformed to a scale from 0 to 100 where higher scores indicate better quality of life. A positive change from Baseline in HRQL score indicates improvement. |
| Change From Baseline to Week 12 in Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) | Baseline and Week 12 | Brain derived neurotrophic factor (uBDNF) and creatinine (Cr) were measured from urine samples by the central laboratories. uBDNF/Cr was derived by dividing uBDNF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant. |
| Change From Baseline to Week 12 in Total Urinary Nerve Growth Factor Normalized by Urine Creatinine | Baseline and Week 12 | Total (acidified) urinary nerve growth factor (uNGF) and creatinine (Cr) were measured from urine samples by the central laboratories. Total uNGF/Cr was derived by dividing total uNGF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant. |
| Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Baseline and Week 12 | The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 1: 'Does not cause me any problems at all'; 2: 'Causes me some very minor problems'; 3: 'Causes me some minor problems'; 4: 'Causes me (some) moderate problems'; 5: 'Causes me severe problems' and 6: 'Causes me many severe problems'. Improvement: ≥ 1 point improvement compared to Baseline; Major Improvement: ≥ 2 point improvement compared to Baseline; Deterioration: ≥ 1 point deterioration compared to Baseline. |
| Change From Baseline to Week 12 in Total Urgency Score | Baseline and Week 12 | The intensity of urgency of each micturition (urination) and incontinence episode (any involuntary leakage of urine) was recorded by the participant in an electronic diary according to the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The total urgency score was calculated by adding all PPIUS scores over a 3-day period prior to the Baseline and Week 12 visits for each participant. |
| Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) at Week 12 | Week 12 | Brain derived neurotrophic factor (uBDNF) and creatinine (Cr) were measured from urine samples by the central laboratories. uBDNF/Cr was derived by dividing uBDNF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant. |
Countries
Austria, Belgium, Bulgaria, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Norway, Poland, Romania, Russia, Slovakia, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received 2 placebo tablets once daily for 12 weeks. | 186 |
| Solifenacin 5 mg Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks. | 182 |
| Solifenacin 10 mg Participants received two 5 mg solifenacin tablets once daily for 12 weeks. | 175 |
| Total | 543 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 | 2 |
| Overall Study | Lack of Efficacy | 2 | 1 | 1 |
| Overall Study | Other | 1 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 7 | 2 |
Baseline characteristics
| Characteristic | Solifenacin 5 mg | Total | Solifenacin 10 mg | Placebo |
|---|---|---|---|---|
| Age, Continuous | 55.5 years STANDARD_DEVIATION 13 | 54.9 years STANDARD_DEVIATION 13.1 | 55.5 years STANDARD_DEVIATION 13.3 | 53.7 years STANDARD_DEVIATION 13 |
| Race/Ethnicity, Customized Asian | 1 participants | 7 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 4 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Other | 3 participants | 13 participants | 6 participants | 4 participants |
| Race/Ethnicity, Customized White | 177 participants | 519 participants | 165 participants | 177 participants |
| Sex: Female, Male Female | 182 Participants | 543 Participants | 175 Participants | 186 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 186 | 21 / 182 | 34 / 175 |
| serious Total, serious adverse events | 1 / 186 | 1 / 182 | 4 / 175 |
Outcome results
Primary
Change From Baseline to Week 12 in Bladder Wall Thickness
Bladder wall thickness (BWT) measurements were obtained using transvaginal ultrasound. The BWT was derived as one mean value per image pooled over measurements of 3 locations (anterior wall, dome and trigone), and performed by 2 central readers and 1 adjudicator.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT): all randomized participants who received at least 1 dose of randomized study medication and who had a mean BWT measurement at Baseline. Analysis includes participants with available data; Last observation carried forward (LOCF) of post-baseline data was used for imputation of missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Bladder Wall Thickness | 0.00 mm | Standard Deviation 1.26 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Bladder Wall Thickness | -0.29 mm | Standard Deviation 1.37 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Bladder Wall Thickness | -0.18 mm | Standard Deviation 1.18 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Bladder Wall Thickness | -0.24 mm | Standard Deviation 1.28 |
Comparison: The null hypothesis was that the mean change from Baseline in BWT in the pooled solifenacin group and placebo was the same. Estimated as two-sided contrast with 95% confidence interval. Power was planned for 80% (assumption: mean difference = 0.5 mm, standard deviation=1.65, 314 and 157 participants, bonferroni adjustment for alpha =0.025)p-value: 0.09595% CI: [-0.368, 0.03]ANCOVA
Primary
Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12
Free (neutralized) urinary nerve growth factor (uNGF) and creatinine (Cr) were measured from urine samples by the central laboratories. Free (neutralized) uNGF/Cr was derived by dividing free (neutralized) uNGF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant.
Time frame: Week 12
Population: Full Analysis Set urinary Nerve Growth Factor subset (FAS\_uNGF0): all randomized participants who received at least 1 dose of randomized study medication and who had an uNGF/Cr measurement at Baseline and on at least 1 visit thereafter, excluding participants with Baseline uNGF below or equal to the laboratory quantification limit. LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | 30.359 pg/µmol | Standard Deviation 26.176 |
| Solifenacin 5 mg | Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | 31.855 pg/µmol | Standard Deviation 29.4371 |
| Solifenacin 10 mg | Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | 38.917 pg/µmol | Standard Deviation 60.3231 |
| Pooled Solifenacin | Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | 35.325 pg/µmol | Standard Deviation 47.2694 |
Comparison: The null hypothesis for the co-primary treatment comparison was that the mean free (neutralized) uNGF/Cr value in the pooled solifenacin group and placebo was the same. Wilcoxon rank-sum test was used instead of a contrast from analysis of covariance (ANCOVA), because data was not normally distributed. Power was planned for 80% (assumption: mean difference = 0.74 pg/μmol, standard deviation=2.0, 220 and 110 participants, bonferroni adjustment for alpha =0.025).p-value: 0.25Wilcoxon (Mann-Whitney)
Secondary
Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) at Week 12
Brain derived neurotrophic factor (uBDNF) and creatinine (Cr) were measured from urine samples by the central laboratories. uBDNF/Cr was derived by dividing uBDNF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant.
Time frame: Week 12
Population: Full Analysis Set urinary Brain Derived Neurotrophic Factor (FAS\_uBDNF): all randomized participants who received at least 1 dose of randomized study medication, who had given consent for additional analysis and who had an uBDNF/Cr measurement at baseline and on at least 1 visit thereafter. LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) at Week 12 | 116.9 pg/µmol | Standard Deviation 260.5 |
| Solifenacin 5 mg | Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) at Week 12 | 158.1 pg/µmol | Standard Deviation 483 |
| Solifenacin 10 mg | Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) at Week 12 | 160.4 pg/µmol | Standard Deviation 373 |
| Pooled Solifenacin | Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) at Week 12 | 159.2 pg/µmol | Standard Deviation 431.6 |
Secondary
Change From Baseline in EuroQoL 5-Dimension Questionnaire Visual Analog Scale
The participants' quality of life was assessed using the EuroQoL 5 Dimension Questionnaire (EQ-5D) visual analog scale (VAS). Health status is completed by the participant indicating their own health state today by drawing a line on a vertical scale from 0 to 100 where the endpoints are labeled 'Worst imaginable health state' (=0) and 'Best imaginable health state' (=100). On the EQ-5D VAS, a positive change from Baseline indicates improvement.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in EuroQoL 5-Dimension Questionnaire Visual Analog Scale | 3.60 units on a scale | Standard Deviation 16.86 |
| Solifenacin 5 mg | Change From Baseline in EuroQoL 5-Dimension Questionnaire Visual Analog Scale | 4.80 units on a scale | Standard Deviation 20.22 |
| Solifenacin 10 mg | Change From Baseline in EuroQoL 5-Dimension Questionnaire Visual Analog Scale | 5.10 units on a scale | Standard Deviation 17.86 |
| Pooled Solifenacin | Change From Baseline in EuroQoL 5-Dimension Questionnaire Visual Analog Scale | 4.90 units on a scale | Standard Deviation 19.12 |
Secondary
Change From Baseline in Health-Related Quality of Life (HRQL)
Health-related quality of life was assessed by the Overactive Bladder Symptom and Health-Related Quality of Life Questionnaire (OAB-q). The OAB-q is a patient-administered instrument comprising of an 8-item symptom bother scale (see previous outcome measure) and 25 HRQL items comprising 4 subscales (concern, coping, social interaction and sleep) and a total HRQL score. Participants were asked how their overall bladder symptoms had affected their life in the past 4 weeks. Each of the 25 HRQL questions has a 6-point Likert scale response ranging from 'none of the time' (1) to 'all of the time' (6). The HRQL subscale scores were calculated by summing the responses of the items within each subscale.The HRQL total score was calculated by adding the 4 HRQL subscale scores,. All scores were transformed to a scale from 0 to 100 where higher scores indicate better quality of life. A positive change from Baseline in HRQL score indicates improvement.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Health-Related Quality of Life (HRQL) | Sleep subscale | 10.80 units on a scale | Standard Deviation 19.31 |
| Placebo | Change From Baseline in Health-Related Quality of Life (HRQL) | Coping subscale | 12.40 units on a scale | Standard Deviation 18.85 |
| Placebo | Change From Baseline in Health-Related Quality of Life (HRQL) | Social interaction subscale | 8.70 units on a scale | Standard Deviation 16.95 |
| Placebo | Change From Baseline in Health-Related Quality of Life (HRQL) | Concern subscale | 13.80 units on a scale | Standard Deviation 18.64 |
| Placebo | Change From Baseline in Health-Related Quality of Life (HRQL) | Total score | 11.72 units on a scale | Standard Deviation 16.71 |
| Solifenacin 5 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Concern subscale | 20.35 units on a scale | Standard Deviation 22.52 |
| Solifenacin 5 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Sleep subscale | 15.50 units on a scale | Standard Deviation 21.33 |
| Solifenacin 5 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Social interaction subscale | 13.00 units on a scale | Standard Deviation 19.65 |
| Solifenacin 5 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Coping subscale | 18.26 units on a scale | Standard Deviation 20.89 |
| Solifenacin 5 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Total score | 17.25 units on a scale | Standard Deviation 19.74 |
| Solifenacin 10 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Concern subscale | 20.77 units on a scale | Standard Deviation 18.73 |
| Solifenacin 10 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Total score | 17.69 units on a scale | Standard Deviation 15.75 |
| Solifenacin 10 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Coping subscale | 20.21 units on a scale | Standard Deviation 19.42 |
| Solifenacin 10 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Sleep subscale | 15.10 units on a scale | Standard Deviation 15.95 |
| Solifenacin 10 mg | Change From Baseline in Health-Related Quality of Life (HRQL) | Social interaction subscale | 12.00 units on a scale | Standard Deviation 15.54 |
| Pooled Solifenacin | Change From Baseline in Health-Related Quality of Life (HRQL) | Sleep subscale | 15.30 units on a scale | Standard Deviation 18.95 |
| Pooled Solifenacin | Change From Baseline in Health-Related Quality of Life (HRQL) | Coping subscale | 19.18 units on a scale | Standard Deviation 20.2 |
| Pooled Solifenacin | Change From Baseline in Health-Related Quality of Life (HRQL) | Total score | 17.46 units on a scale | Standard Deviation 17.94 |
| Pooled Solifenacin | Change From Baseline in Health-Related Quality of Life (HRQL) | Concern subscale | 20.55 units on a scale | Standard Deviation 20.79 |
| Pooled Solifenacin | Change From Baseline in Health-Related Quality of Life (HRQL) | Social interaction subscale | 12.50 units on a scale | Standard Deviation 17.81 |
Secondary
Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 3 or 4 Per 24 Hours
An urgency incontinence episode is defined as any incontinence episode classified by the participant as a grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The average number of grade 3 or 4 urgency incontinence episodes per 24 hours was calculated from the number of urgency incontinence episodes recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits.
Time frame: Baseline and Week 12
Population: Full analysis set participants with grade 3 or 4 urgency incontinence events at Baseline and with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 3 or 4 Per 24 Hours | -0.71 urgency incontinence episodes | Standard Deviation 1.52 |
| Solifenacin 5 mg | Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 3 or 4 Per 24 Hours | -1.32 urgency incontinence episodes | Standard Deviation 1.63 |
| Solifenacin 10 mg | Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 3 or 4 Per 24 Hours | -0.90 urgency incontinence episodes | Standard Deviation 1.23 |
| Pooled Solifenacin | Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 3 or 4 Per 24 Hours | -1.09 urgency incontinence episodes | Standard Deviation 1.43 |
Secondary
Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 4 Per 24 Hours
An urgency incontinence episode is defined as any incontinence episode classified by the participant as a grade 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The average number of grade 4 urgency incontinence episodes per 24 hours was calculated from the number of urgency incontinence episodes recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits.
Time frame: Baseline and Week 12
Population: Full analysis set participants with grade 4 urgency incontinence events at Baseline and with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 4 Per 24 Hours | -0.70 urgency incontinence episodes | Standard Deviation 1.46 |
| Solifenacin 5 mg | Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 4 Per 24 Hours | -0.96 urgency incontinence episodes | Standard Deviation 0.91 |
| Solifenacin 10 mg | Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 4 Per 24 Hours | -0.70 urgency incontinence episodes | Standard Deviation 1.16 |
| Pooled Solifenacin | Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 4 Per 24 Hours | -0.82 urgency incontinence episodes | Standard Deviation 1.06 |
Secondary
Change From Baseline in Patient Assessment of Treatment Satisfaction
The treatment satisfaction visual analog scale (TS\_VAS) asks patients to rate their satisfaction with treatment by placing a vertical mark on a 100 mm line where the endpoints are labeled 'No, not at all' on the left (score = 0) to 'Yes, completely satisfied' on the right (score = 100). A positive change from Baseline indicates improvement.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient Assessment of Treatment Satisfaction | 18.90 units on a scale | Standard Deviation 42.18 |
| Solifenacin 5 mg | Change From Baseline in Patient Assessment of Treatment Satisfaction | 24.90 units on a scale | Standard Deviation 39.58 |
| Solifenacin 10 mg | Change From Baseline in Patient Assessment of Treatment Satisfaction | 31.90 units on a scale | Standard Deviation 41.02 |
| Pooled Solifenacin | Change From Baseline in Patient Assessment of Treatment Satisfaction | 28.20 units on a scale | Standard Deviation 40.36 |
Secondary
Change From Baseline in Patient Assessment of Urgency Bother
The participants' perception and impression of bother associated with their condition were assessed using the Urgency Bother-Visual Analog Scale (UB-VAS). The participant was asked to place a vertical mark on a 100 mm line to indicate how much bother has urgency been for them in the past week, whereby 'no bother at all' is represented on the left end (score = 0) and 'worst possible bother' (score = 100) at the right end of the line. A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient Assessment of Urgency Bother | -12.60 units on a scale | Standard Deviation 29.51 |
| Solifenacin 5 mg | Change From Baseline in Patient Assessment of Urgency Bother | -27.70 units on a scale | Standard Deviation 30.39 |
| Solifenacin 10 mg | Change From Baseline in Patient Assessment of Urgency Bother | -28.90 units on a scale | Standard Deviation 28.72 |
| Pooled Solifenacin | Change From Baseline in Patient Assessment of Urgency Bother | -28.20 units on a scale | Standard Deviation 29.57 |
Secondary
Change From Baseline in Patient Perception of Bladder Condition (PPBC)
The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 1: 'Does not cause me any problems at all'; 2: 'Causes me some very minor problems'; 3: 'Causes me some minor problems'; 4: 'Causes me (some) moderate problems'; 5: 'Causes me severe problems' and 6: 'Causes me many severe problems'. A negative change from Baseline score indicates improvement.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | -0.7 units on a scale | Standard Deviation 1.33 |
| Solifenacin 5 mg | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | -1.3 units on a scale | Standard Deviation 1.38 |
| Solifenacin 10 mg | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | -1.3 units on a scale | Standard Deviation 1.26 |
| Pooled Solifenacin | Change From Baseline in Patient Perception of Bladder Condition (PPBC) | -1.3 units on a scale | Standard Deviation 1.33 |
Secondary
Change From Baseline in Symptom Bother Score
Overactive bladder symptoms were assessed using the symptom bother scale of the Overactive Bladder Symptom and Health-Related Quality of Life Questionnaire (OAB-q). The OAB-q is a patient-administered instrument comprising an 8-item symptom bother scale and 25 health-related quality of life items (see next outcome measure). In the symptom bother scale participants were asked how much they had been bothered by selected bladder symptoms during the past 4 weeks. Each question has a 6-point Likert scale response ranging from 'not at all' (1) to 'a very great deal' (6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 to 100, with 100 indicating worst severity. A negative change from Baseline in symptom bother score indicates improvement.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Symptom Bother Score | -14.90 units on a scale | Standard Deviation 19.11 |
| Solifenacin 5 mg | Change From Baseline in Symptom Bother Score | -22.32 units on a scale | Standard Deviation 20.59 |
| Solifenacin 10 mg | Change From Baseline in Symptom Bother Score | -22.91 units on a scale | Standard Deviation 18.69 |
| Pooled Solifenacin | Change From Baseline in Symptom Bother Score | -22.60 units on a scale | Standard Deviation 19.69 |
Secondary
Change From Baseline to Week 12 in Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr)
Brain derived neurotrophic factor (uBDNF) and creatinine (Cr) were measured from urine samples by the central laboratories. uBDNF/Cr was derived by dividing uBDNF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant.
Time frame: Baseline and Week 12
Population: Full Analysis Set urinary Brain Derived Neurotrophic Factor (FAS\_uBDNF); LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) | -27.4 pg/µmol | Standard Deviation 317.6 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) | 31.1 pg/µmol | Standard Deviation 426.9 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) | -88.1 pg/µmol | Standard Deviation 980.6 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) | -27.8 pg/µmol | Standard Deviation 754.4 |
Secondary
Change From Baseline to Week 12 in Mean Level of Urgency
The intensity of urgency of each micturition (urination) and incontinence episode (any involuntary leakage of urine) was recorded by the participant in an electronic diary according to the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The mean level of urgency was calculated by adding the PPIUS grade for all events (micturition or incontinence) and dividing by the number of episodes recorded in the diary over 3 days prior to the Baseline and Week 12 visits.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Mean Level of Urgency | -0.15 units on a scale | Standard Deviation 0.525 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Mean Level of Urgency | -0.23 units on a scale | Standard Deviation 0.504 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Mean Level of Urgency | -0.24 units on a scale | Standard Deviation 0.578 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Mean Level of Urgency | -0.23 units on a scale | Standard Deviation 0.539 |
Secondary
Change From Baseline to Week 12 in Mean Number of Events (Micturitions Plus Incontinence Episodes) Per 24 Hours
The average number of micturitions (urinations) and incontinence episodes (any involuntary leakage of urine) per day was derived from the number of events recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Mean Number of Events (Micturitions Plus Incontinence Episodes) Per 24 Hours | -1.40 events | Standard Deviation 3 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Mean Number of Events (Micturitions Plus Incontinence Episodes) Per 24 Hours | -2.44 events | Standard Deviation 3.55 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Mean Number of Events (Micturitions Plus Incontinence Episodes) Per 24 Hours | -1.80 events | Standard Deviation 2.63 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Mean Number of Events (Micturitions Plus Incontinence Episodes) Per 24 Hours | -2.13 events | Standard Deviation 3.16 |
Secondary
Change From Baseline to Week 12 in Mean Number of Incontinence Episodes Per 24 Hours
The average number of incontinence episodes (any involuntary leakage of urine) per 24 hours was calculated from the number of incontinence episodes recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits.
Time frame: Baseline and Week 12
Population: Full analysis set participants with incontinence events at Baseline and with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Mean Number of Incontinence Episodes Per 24 Hours | -0.60 incontinence episodes | Standard Deviation 1.65 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Mean Number of Incontinence Episodes Per 24 Hours | -1.49 incontinence episodes | Standard Deviation 1.65 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Mean Number of Incontinence Episodes Per 24 Hours | -1.04 incontinence episodes | Standard Deviation 1.76 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Mean Number of Incontinence Episodes Per 24 Hours | -1.24 incontinence episodes | Standard Deviation 1.72 |
Secondary
Change From Baseline to Week 12 in Mean Number of Micturitions Per 24 Hours
The average number of micturitions (urinations) per 24 hours was derived from the number of micturitions recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Mean Number of Micturitions Per 24 Hours | -1.18 micturitions | Standard Deviation 3.03 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Mean Number of Micturitions Per 24 Hours | -1.80 micturitions | Standard Deviation 3.77 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Mean Number of Micturitions Per 24 Hours | -1.28 micturitions | Standard Deviation 2.61 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Mean Number of Micturitions Per 24 Hours | -1.55 micturitions | Standard Deviation 3.28 |
Secondary
Change From Baseline to Week 12 in Mean Number of Urgency Events Per 24 Hours
The intensity of urgency of each micturition (urination) and incontinence episode (any involuntary leakage of urine) was recorded by the participant in an electronic diary according to the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. An urgency event is defined as any micturition or incontinence episode classified by the participant as a grade 3 or 4 on the PPIUS scale. The average number of urgency events per day is derived from the diary data completed by participants on the 3 days prior to the Baseline and Week 12 visits.
Time frame: 12 weeks
Population: Full analysis set participants with events at Baseline and with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Mean Number of Urgency Events Per 24 Hours | -1.58 urgency events | Standard Deviation 3.04 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Mean Number of Urgency Events Per 24 Hours | -2.22 urgency events | Standard Deviation 3.09 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Mean Number of Urgency Events Per 24 Hours | -1.88 urgency events | Standard Deviation 2.71 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Mean Number of Urgency Events Per 24 Hours | -2.06 urgency events | Standard Deviation 2.91 |
Secondary
Change From Baseline to Week 12 in Mean Number of Urgency Micturitions Per 24 Hours
An urgency micturition is defined as any micturition classified by the participant as a grade 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The average number of urgency micturitions per 24 hours was derived from the number of urgency micturitions recorded by the participant in an electronic diary for 3 days before the Baseline and Week 12 clinic visits.
Time frame: Baseline and Week 12
Population: Full Analysis Set participants with urgency micturitions at Baseline and with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Mean Number of Urgency Micturitions Per 24 Hours | -1.35 urgency micturitions | Standard Deviation 2.86 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Mean Number of Urgency Micturitions Per 24 Hours | -1.77 urgency micturitions | Standard Deviation 2.99 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Mean Number of Urgency Micturitions Per 24 Hours | -1.60 urgency micturitions | Standard Deviation 2.45 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Mean Number of Urgency Micturitions Per 24 Hours | -1.69 urgency micturitions | Standard Deviation 2.75 |
Secondary
Change From Baseline to Week 12 in Total Urgency Score
The intensity of urgency of each micturition (urination) and incontinence episode (any involuntary leakage of urine) was recorded by the participant in an electronic diary according to the Patient Perception of Intensity of Urgency Scale (PPIUS) as follows: 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could postpone voiding a short while; 3 = Severe urgency, could not postpone voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The total urgency score was calculated by adding all PPIUS scores over a 3-day period prior to the Baseline and Week 12 visits for each participant.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Total Urgency Score | -13.61 units on a scale | Standard Deviation 25.98 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Total Urgency Score | -22.39 units on a scale | Standard Deviation 29.8 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Total Urgency Score | -16.91 units on a scale | Standard Deviation 22.57 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Total Urgency Score | -19.81 units on a scale | Standard Deviation 26.73 |
Secondary
Change From Baseline to Week 12 in Total Urinary Nerve Growth Factor Normalized by Urine Creatinine
Total (acidified) urinary nerve growth factor (uNGF) and creatinine (Cr) were measured from urine samples by the central laboratories. Total uNGF/Cr was derived by dividing total uNGF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant.
Time frame: Baseline and Week 12
Population: Full Analysis Set urinary Nerve Growth Factor subset (FAS\_uNGF0) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 12 in Total Urinary Nerve Growth Factor Normalized by Urine Creatinine | -0.962 pg/µmol | Standard Deviation 24.2241 |
| Solifenacin 5 mg | Change From Baseline to Week 12 in Total Urinary Nerve Growth Factor Normalized by Urine Creatinine | 2.758 pg/µmol | Standard Deviation 49.0191 |
| Solifenacin 10 mg | Change From Baseline to Week 12 in Total Urinary Nerve Growth Factor Normalized by Urine Creatinine | 3.858 pg/µmol | Standard Deviation 44.0421 |
| Pooled Solifenacin | Change From Baseline to Week 12 in Total Urinary Nerve Growth Factor Normalized by Urine Creatinine | 3.302 pg/µmol | Standard Deviation 46.5612 |
Secondary
Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness
Bladder wall thickness (BWT) measurements were obtained using transvaginal ultrasound. The BWT was derived as one mean value per image pooled over measurements of 3 locations (anterior wall, dome and trigone), and performed by 2 central readers and 1 adjudicator.
Time frame: Baseline, Week 6 and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data at each time point (indicated by n).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Week 6 (n=157, 145, 141, 286) | -0.01 mm | Standard Deviation 1.16 |
| Placebo | Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Week 12 (n=160, 143, 135, 278) | 0.02 mm | Standard Deviation 1.28 |
| Solifenacin 5 mg | Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Week 12 (n=160, 143, 135, 278) | -0.26 mm | Standard Deviation 1.37 |
| Solifenacin 5 mg | Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Week 6 (n=157, 145, 141, 286) | -0.04 mm | Standard Deviation 1.27 |
| Solifenacin 10 mg | Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Week 6 (n=157, 145, 141, 286) | -0.14 mm | Standard Deviation 1.15 |
| Solifenacin 10 mg | Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Week 12 (n=160, 143, 135, 278) | -0.22 mm | Standard Deviation 1.18 |
| Pooled Solifenacin | Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Week 6 (n=157, 145, 141, 286) | -0.09 mm | Standard Deviation 1.21 |
| Pooled Solifenacin | Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness | Week 12 (n=160, 143, 135, 278) | -0.24 mm | Standard Deviation 1.28 |
Secondary
Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine
Free (neutralized) urinary nerve growth factor (uNGF) and creatinine (Cr) were measured from urine samples by the central laboratories. Free (neutralized) uNGF/Cr was derived by dividing free (neutralized) uNGF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant.
Time frame: Baseline, Week 6 and Week 12
Population: Full Analysis Set urinary Nerve Growth Factor subset (FAS\_uNGF0) participants with available data at each time point (indicated by n).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Week 6 (n=168, 163, 160, 323) | -4.638 pg/µmol | Standard Deviation 30.7301 |
| Placebo | Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Week 12 (n=173, 171, 166, 337) | -1.318 pg/µmol | Standard Deviation 27.9927 |
| Solifenacin 5 mg | Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Week 12 (n=173, 171, 166, 337) | 0.801 pg/µmol | Standard Deviation 33.312 |
| Solifenacin 5 mg | Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Week 6 (n=168, 163, 160, 323) | 4.650 pg/µmol | Standard Deviation 38.3159 |
| Solifenacin 10 mg | Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Week 12 (n=173, 171, 166, 337) | 2.625 pg/µmol | Standard Deviation 44.0319 |
| Solifenacin 10 mg | Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Week 6 (n=168, 163, 160, 323) | 4.309 pg/µmol | Standard Deviation 89.1963 |
| Pooled Solifenacin | Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Week 12 (n=173, 171, 166, 337) | 1.699 pg/µmol | Standard Deviation 38.915 |
| Pooled Solifenacin | Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine | Week 6 (n=168, 163, 160, 323) | 4.481 pg/µmol | Standard Deviation 68.3171 |
Secondary
Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D
The participants' quality of life was assessed using the EuroQoL 5 Dimension Questionnaire (EQ-5D). The EQ-5D is a standardized instrument for use as a measure of health outcome and is based on the following 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. For each dimension participants were asked to select the statement which best described their health that day, from level 1 (indicating no problems) to 3 (indicating extreme problems/unable to perform). Improvement was defined as a change from a state of being unable to perform or extreme problems at Baseline to no problems or to some or moderate problems at Week 12, and from some or moderate problems to no problems. Worsening was defined as a change from no problems at Baseline to some or moderate problems or to a state of being unable to perform or extreme problems at Week 12, and from some or moderate problems to a state of being unable to perform or extreme problems.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Usual Activities: Worsening | 7.9 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Usual Activities: Improvement | 7.9 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Self-care: Worsening | 2.4 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Anxiety/Depression: Worsening | 10.3 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Anxiety/Depression: Improvement | 17.0 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Mobility: Worsening | 10.3 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Mobility: Improvement | 6.7 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Pain/Discomfort: Worsening | 10.3 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Pain/Discomfort: Improvement | 15.2 percentage of participants |
| Placebo | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Self-care: Improvement | 2.4 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Self-care: Improvement | 3.9 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Mobility: Improvement | 10.3 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Mobility: Worsening | 7.1 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Self-care: Worsening | 3.2 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Usual Activities: Improvement | 7.7 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Usual Activities: Worsening | 11.0 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Pain/Discomfort: Improvement | 19.4 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Pain/Discomfort: Worsening | 11.0 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Anxiety/Depression: Improvement | 17.4 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Anxiety/Depression: Worsening | 11.0 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Self-care: Improvement | 3.4 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Usual Activities: Worsening | 4.8 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Mobility: Improvement | 9.6 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Pain/Discomfort: Improvement | 18.5 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Mobility: Worsening | 3.4 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Pain/Discomfort: Worsening | 4.8 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Anxiety/Depression: Worsening | 13.7 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Self-care: Worsening | 4.1 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Anxiety/Depression: Improvement | 19.9 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Usual Activities: Improvement | 11.0 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Self-care: Worsening | 3.7 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Anxiety/Depression: Improvement | 18.6 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Pain/Discomfort: Worsening | 8.0 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Usual Activities: Worsening | 8.0 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Mobility: Worsening | 5.3 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Mobility: Improvement | 10.0 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Self-care: Improvement | 3.7 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Pain/Discomfort: Improvement | 18.9 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Usual Activities: Improvement | 9.3 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D | Anxiety/Depression: Worsening | 12.3 percentage of participants |
Secondary
Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC)
The PPBC scale is a global assessment tool that asks patients to rate their impression of their current bladder condition on a 6-point scale from 1: 'Does not cause me any problems at all'; 2: 'Causes me some very minor problems'; 3: 'Causes me some minor problems'; 4: 'Causes me (some) moderate problems'; 5: 'Causes me severe problems' and 6: 'Causes me many severe problems'. Improvement: ≥ 1 point improvement compared to Baseline; Major Improvement: ≥ 2 point improvement compared to Baseline; Deterioration: ≥ 1 point deterioration compared to Baseline.
Time frame: Baseline and Week 12
Population: Full Analysis Set Bladder Wall Thickness (FAS\_BWT) participants with available data; LOCF was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Major Improvement | 27.4 percentage of participants |
| Placebo | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | No change | 34.9 percentage of participants |
| Placebo | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Deterioration | 15.4 percentage of participants |
| Placebo | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Improvement | 49.7 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | No change | 21.6 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Improvement | 71.9 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Deterioration | 6.4 percentage of participants |
| Solifenacin 5 mg | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Major Improvement | 39.8 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Deterioration | 5.2 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | No change | 20.3 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Improvement | 74.5 percentage of participants |
| Solifenacin 10 mg | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Major Improvement | 44.4 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | No change | 21.0 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Deterioration | 5.9 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Major Improvement | 42.0 percentage of participants |
| Pooled Solifenacin | Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC) | Improvement | 73.1 percentage of participants |
Secondary
Total Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12
Total (acidified) urinary nerve growth factor (uNGF) and creatinine (Cr) were measured from urine samples by the central laboratories. Total uNGF/Cr was derived by dividing total uNGF concentrations \[pg/mL\] by the urine creatinine concentrations (µmol/mL) from the same participant.
Time frame: Week 12
Population: Full Analysis Set urinary Nerve Growth Factor subset (FAS\_uNGF0) participants with available data; LOCF was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | 26.564 pg/µmol | Standard Deviation 23.0347 |
| Solifenacin 5 mg | Total Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | 30.135 pg/µmol | Standard Deviation 47.4089 |
| Solifenacin 10 mg | Total Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | 34.199 pg/µmol | Standard Deviation 56.218 |
| Pooled Solifenacin | Total Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12 | 32.143 pg/µmol | Standard Deviation 51.9123 |