SHRINK: Study of 2 Doses of Solifenacin Succinate in Female Subjects With Overactive Bladder.

• Sponsor: Astellas Pharma Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01093534
• Collaborator: (none)
• Enrollment: 547
• Locations: 79
• Arms: 3
• Duration (Months): 17
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Detrusor Overactivity; Overactive Bladder	Drug: Placebo; Drug: solifenacin	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 547 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A Study to Evaluate the Overall Effect of Solifenacin 5mg and 10mg on Bladder Wall Thickness and Urinary Nerve Growth Factor in Female Subjects With Overactive Bladder and a Diagnosis of Detrusor Overactivity - A Double-blind, Randomised, Placebo-controlled, Parallel Group, Multi-centre Study.
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received 2 placebo tablets once daily for 12 weeks.	Drug: Placebo; Matching solifenacin placebo tablet
Experimental: Solifenacin 5 mg Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Drug: Placebo; Matching solifenacin placebo tablet; Drug: solifenacin; Tablet for oral administration; Other Names: YM905 Vesicare
Experimental: Solifenacin 10 mg Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Drug: solifenacin; Tablet for oral administration; Other Names: YM905 Vesicare

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		New York	New York	United States	11530
2		New York	New York	United States	12601
3		West Reading	Pennsylvania	United States	19611
4		Graz		Austria	A-8036
5		Linz		Austria	4020
6		Linz		Austria	A-4020
7		Edegem		Belgium	2650
8		Gent		Belgium	9000
9		Kortrijk		Belgium	8500
10		Sofia		Bulgaria	1431
11		Sofia		Bulgaria	1606
12		Varba		Bulgaria	9010
13		Victoria	British Columbia	Canada	V8T 5G1
14		Victoria	British Columbia	Canada	V8V 3N1
15		Barrie	Ontario	Canada	L4M 7G1
16		Brampton	Ontario	Canada	L6T 4S5
17		Brantford	Ontario	Canada	N3R 4N3
18		Kitchener	Ontario	Canada	N2N 2B9
19		Toronto	Ontario	Canada	M4N 3M5
20		Sherbrooke	Quebec	Canada	J1H 5N4
21		Brno		Czech Republic	625 00
22		Hradec Kralove		Czech Republic	500 05
23		Podoli		Czech Republic	147 00
24		Marseille		France	13285
25		Paris		France	75970
26		Aachen		Germany	52074
27		Berlin		Germany	10115
28		Hannover		Germany	30625
29		Munich		Germany	81679
30		Budapest		Hungary	1082
31		Budapest		Hungary	1115
32		Szeged		Hungary	6725
33		Szekesfehervar		Hungary	8000
34		Haifa		Israel	31096
35		Petah Tikva		Israel	49100
36		Ramat Gan		Israel	52621
37		Avellino		Italy	83100
38		Milan		Italy	20132
39		Milan		Italy	20153
40		Rome		Italy	00133
41		Varese		Italy	21100
42		Arendal		Norway	4809
43		Drammen		Norway	3004
44		Haugesund		Norway	5507
45		Tonsberg		Norway	3103
46		Bydgoszcz		Poland	85-094
47		Krakow		Poland	31-530
48		Warszawa		Poland	00-846
49		Warszawa		Poland	01-432
50		Warszawa		Poland	02-005
51		Warszawa		Poland	02-929
52		Timisoara		Romania	300376
53		Moscow		Russian Federation	101000
54		Moscow		Russian Federation	105425
55		Moscow		Russian Federation	115516
56		Moscow		Russian Federation	117815
57		Moscow		Russian Federation	117997
58		Moscow		Russian Federation	119435
59		Moscow		Russian Federation	123836
60		Moscow		Russian Federation	125206
61		Nizhniy Novgorod		Russian Federation	603018
62		Saint Peterburg		Russian Federation	197089
63		Saint Peterburg		Russian Federation	199044
64		Yaroslavl'		Russian Federation
65		Bardejov		Slovakia	085 01
66		Martin		Slovakia	036 59
67		Zilina		Slovakia	010 01
68		Barcelona		Spain	08036
69		Madrid		Spain	28031
70		Madrid		Spain	28046
71		Madrid		Spain	28905
72		Lund		Sweden	22185
73		Stockholm		Sweden	14186
74		Ankara		Turkey	06018
75		Istanbul		Turkey	34664
76		Kocaeli		Turkey	41380
77		Harrow		United Kingdom	HA1 3JU
78		London		United Kingdom	SE5 9RS
79		London		United Kingdom	W2 2YP

Sponsors and Collaborators

• Astellas Pharma Inc

Investigators

• Study Chair: Use Central Contact, Astellas Pharma Europe B.V.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Link to results on Astellas Clinical Study Results website

Publications

None provided.

• Responsible Party: Astellas Pharma Inc
• ClinicalTrials.gov Identifier: NCT01093534
• Other Study ID Numbers: 905-EC-007; 2008-005215-17
• First Posted: Mar 26, 2010
• Last Update Posted: Mar 21, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Astellas Pharma Inc: Vesicare; Solifenacin; Detrusor Overactivity; Urinary Nerve Growth Factor; Overactive Bladder; Bladder wall thickness
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Solifenacin Succinate

Study Results

Participant Flow

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.
Period Title: Overall Study
STARTED	186	183	178
Received Study Treatment	186	182	175
COMPLETED	176	167	169
NOT COMPLETED	10	16	9

Baseline Characteristics

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Total
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Total of all reporting groups
Overall Participants	186	182	175	543
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.7 (13.0)	55.5 (13.0)	55.5 (13.3)	54.9 (13.1)
Sex: Female, Male (Count of Participants)
Female	186 100%	182 100%	175 100%	543 100%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	177 95.2%	177 97.3%	165 94.3%	519 95.6%
Black or African American	1 0.5%	1 0.5%	2 1.1%	4 0.7%
Asian	4 2.2%	1 0.5%	2 1.1%	7 1.3%
Other	4 2.2%	3 1.6%	6 3.4%	13 2.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 12 in Bladder Wall Thickness
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	168	160	150	310
Mean (Standard Deviation) [mm]	0.00 (1.26)	-0.29 (1.37)	-0.18 (1.18)	-0.24 (1.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Solifenacin
	Comments	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)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments	Hochberg Method for controlling the overall risk of type I error of 5% was used to adjust for using two co-primary endpoints.
	Method	ANCOVA
	Comments	ANCOVA model with fixed effects for treatment and region and Baseline of least squares mean BWT as a covariate.
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.169
	Confidence Interval	(2-Sided) 95%; -0.368 to 0.030
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	176	175	169	344
Mean (Standard Deviation) [pg/µmol]	30.359 (26.1760)	31.855 (29.4371)	38.917 (60.3231)	35.325 (47.2694)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pooled Solifenacin
	Comments	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).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.250
	Comments	Hochberg Method for controlling the overall risk of type I error of 5% was used to adjust for using two co-primary endpoints.
	Method	Wilcoxon (Mann-Whitney)
	Comments	Nonparametric Wilcoxon rank-sum test does not adjust for other factors.

3. Secondary Outcome

Title	Total Urinary Nerve Growth Factor Normalized by Urine Creatinine at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set urinary Nerve Growth Factor subset (FAS_uNGF0) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	176	173	169	342
Mean (Standard Deviation) [pg/µmol]	26.564 (23.0347)	30.135 (47.4089)	34.199 (56.2180)	32.143 (51.9123)

4. Secondary Outcome

Title	Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr) at Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	170	170	166	336
Mean (Standard Deviation) [pg/µmol]	116.9 (260.5)	158.1 (483.0)	160.4 (373.0)	159.2 (431.6)

5. Secondary Outcome

Title	Change From Baseline to Week 6 and Week 12 in Bladder Wall Thickness
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data at each time point (indicated by n).

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	175	171	155	326
Week 6 (n=157, 145, 141, 286)	-0.01 (1.16)	-0.04 (1.27)	-0.14 (1.15)	-0.09 (1.21)
Week 12 (n=160, 143, 135, 278)	0.02 (1.28)	-0.26 (1.37)	-0.22 (1.18)	-0.24 (1.28)

6. Secondary Outcome

Title	Change From Baseline to Week 6 and Week 12 in Neutralized Urinary Nerve Growth Factor Normalized by Urine Creatinine
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set urinary Nerve Growth Factor subset (FAS_uNGF0) participants with available data at each time point (indicated by n).

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	176	175	169	344
Week 6 (n=168, 163, 160, 323)	-4.638 (30.7301)	4.650 (38.3159)	4.309 (89.1963)	4.481 (68.3171)
Week 12 (n=173, 171, 166, 337)	-1.318 (27.9927)	0.801 (33.3120)	2.625 (44.0319)	1.699 (38.9150)

7. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean Number of Events (Micturitions Plus Incontinence Episodes) Per 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	144	137	122	259
Mean (Standard Deviation) [events]	-1.40 (3.00)	-2.44 (3.55)	-1.80 (2.63)	-2.13 (3.16)

8. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean Number of Urgency Events Per 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set participants with events at Baseline and with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	139	133	124	257
Mean (Standard Deviation) [urgency events]	-1.58 (3.04)	-2.22 (3.09)	-1.88 (2.71)	-2.06 (2.91)

9. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean Number of Micturitions Per 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	144	137	122	259
Mean (Standard Deviation) [micturitions]	-1.18 (3.03)	-1.80 (3.77)	-1.28 (2.61)	-1.55 (3.28)

10. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean Number of Urgency Micturitions Per 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set participants with urgency micturitions at Baseline and with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	137	130	117	247
Mean (Standard Deviation) [urgency micturitions]	-1.35 (2.86)	-1.77 (2.99)	-1.60 (2.45)	-1.69 (2.75)

11. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean Number of Incontinence Episodes Per 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set participants with incontinence events at Baseline and with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	67	62	74	136
Mean (Standard Deviation) [incontinence episodes]	-0.60 (1.65)	-1.49 (1.65)	-1.04 (1.76)	-1.24 (1.72)

12. Secondary Outcome

Title	Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 3 or 4 Per 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set participants with grade 3 or 4 urgency incontinence events at Baseline and with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	59	56	69	125
Mean (Standard Deviation) [urgency incontinence episodes]	-0.71 (1.52)	-1.32 (1.63)	-0.90 (1.23)	-1.09 (1.43)

13. Secondary Outcome

Title	Change From Baseline in Mean Number of Urgency Incontinence Episodes With PPIUS Grade 4 Per 24 Hours
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set participants with grade 4 urgency incontinence events at Baseline and with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	50	49	61	110
Mean (Standard Deviation) [urgency incontinence episodes]	-0.70 (1.46)	-0.96 (0.91)	-0.70 (1.16)	-0.82 (1.06)

14. Secondary Outcome

Title	Change From Baseline to Week 12 in Mean Level of Urgency
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	144	137	122	259
Mean (Standard Deviation) [units on a scale]	-0.15 (0.525)	-0.23 (0.504)	-0.24 (0.578)	-0.23 (0.539)

15. Secondary Outcome

Title	Change From Baseline to Week 12 in Total Urgency Score
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	144	137	122	259
Mean (Standard Deviation) [units on a scale]	-13.61 (25.98)	-22.39 (29.80)	-16.91 (22.57)	-19.81 (26.73)

16. Secondary Outcome

Title	Change From Baseline in Patient Perception of Bladder Condition (PPBC)
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	175	171	153	324
Mean (Standard Deviation) [units on a scale]	-0.7 (1.33)	-1.3 (1.38)	-1.3 (1.26)	-1.3 (1.33)

17. Secondary Outcome

Title	Change From Baseline in Patient Assessment of Urgency Bother
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	175	171	153	324
Mean (Standard Deviation) [units on a scale]	-12.60 (29.51)	-27.70 (30.39)	-28.90 (28.72)	-28.20 (29.57)

18. Secondary Outcome

Title	Change From Baseline in Patient Assessment of Treatment Satisfaction
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	175	171	153	324
Mean (Standard Deviation) [units on a scale]	18.90 (42.18)	24.90 (39.58)	31.90 (41.02)	28.20 (40.36)

19. Secondary Outcome

Title	Percentage of Participants With Improvement and Worsening on the 5 Dimensions of the EQ-5D
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	165	155	146	301
Mobility: Improvement	6.7 3.6%	10.3 5.7%	9.6 5.5%	10.0 1.8%
Mobility: Worsening	10.3 5.5%	7.1 3.9%	3.4 1.9%	5.3 1%
Self-care: Improvement	2.4 1.3%	3.9 2.1%	3.4 1.9%	3.7 0.7%
Self-care: Worsening	2.4 1.3%	3.2 1.8%	4.1 2.3%	3.7 0.7%
Usual Activities: Improvement	7.9 4.2%	7.7 4.2%	11.0 6.3%	9.3 1.7%
Usual Activities: Worsening	7.9 4.2%	11.0 6%	4.8 2.7%	8.0 1.5%
Pain/Discomfort: Improvement	15.2 8.2%	19.4 10.7%	18.5 10.6%	18.9 3.5%
Pain/Discomfort: Worsening	10.3 5.5%	11.0 6%	4.8 2.7%	8.0 1.5%
Anxiety/Depression: Improvement	17.0 9.1%	17.4 9.6%	19.9 11.4%	18.6 3.4%
Anxiety/Depression: Worsening	10.3 5.5%	11.0 6%	13.7 7.8%	12.3 2.3%

20. Secondary Outcome

Title	Change From Baseline in EuroQoL 5-Dimension Questionnaire Visual Analog Scale
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	175	171	153	324
Mean (Standard Deviation) [units on a scale]	3.60 (16.86)	4.80 (20.22)	5.10 (17.86)	4.90 (19.12)

21. Secondary Outcome

Title	Change From Baseline in Symptom Bother Score
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	175	171	153	324
Mean (Standard Deviation) [units on a scale]	-14.90 (19.11)	-22.32 (20.59)	-22.91 (18.69)	-22.60 (19.69)

22. Secondary Outcome

Title	Change From Baseline in Health-Related Quality of Life (HRQL)
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	175	171	153	324
Total score	11.72 (16.71)	17.25 (19.74)	17.69 (15.75)	17.46 (17.94)
Coping subscale	12.40 (18.85)	18.26 (20.89)	20.21 (19.42)	19.18 (20.20)
Concern subscale	13.80 (18.64)	20.35 (22.52)	20.77 (18.73)	20.55 (20.79)
Sleep subscale	10.80 (19.31)	15.50 (21.33)	15.10 (15.95)	15.30 (18.95)
Social interaction subscale	8.70 (16.95)	13.00 (19.65)	12.00 (15.54)	12.50 (17.81)

23. Secondary Outcome

Title	Change From Baseline to Week 12 in Brain Derived Neurotrophic Factor Normalized by Urine Creatinine (uBDNF/Cr)
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set urinary Brain Derived Neurotrophic Factor (FAS_uBDNF); LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	170	170	166	336
Mean (Standard Deviation) [pg/µmol]	-27.4 (317.6)	31.1 (426.9)	-88.1 (980.6)	-27.8 (754.4)

24. Secondary Outcome

Title	Change From Baseline to Week 12 in Total Urinary Nerve Growth Factor Normalized by Urine Creatinine
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set urinary Nerve Growth Factor subset (FAS_uNGF0) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	176	173	169	342
Mean (Standard Deviation) [pg/µmol]	-0.962 (24.2241)	2.758 (49.0191)	3.858 (44.0421)	3.302 (46.5612)

25. Secondary Outcome

Title	Percentage of Participants With Improvement or Deterioration in Patient Perception of Bladder Condition (PPBC)
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set Bladder Wall Thickness (FAS_BWT) participants with available data; LOCF was used.

Arm/Group Title	Placebo	Solifenacin 5 mg	Solifenacin 10 mg	Pooled Solifenacin
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.	Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.	Participants received two 5 mg solifenacin tablets once daily for 12 weeks.	Participants received either 5 mg or 10 mg solifenacin once daily for 12 weeks.
Measure Participants	175	171	153	324
Deterioration	15.4 8.3%	6.4 3.5%	5.2 3%	5.9 1.1%
No change	34.9 18.8%	21.6 11.9%	20.3 11.6%	21.0 3.9%
Improvement	49.7 26.7%	71.9 39.5%	74.5 42.6%	73.1 13.5%
Major Improvement	27.4 14.7%	39.8 21.9%	44.4 25.4%	42.0 7.7%

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Placebo		Solifenacin 5 mg		Solifenacin 10 mg
Arm/Group Description	Participants received 2 placebo tablets once daily for 12 weeks.		Participants received one 5 mg solifenacin tablet and one placebo tablet, once daily for 12 weeks.		Participants received two 5 mg solifenacin tablets once daily for 12 weeks.
All Cause Mortality
	Placebo		Solifenacin 5 mg		Solifenacin 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Solifenacin 5 mg		Solifenacin 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/186 (0.5%)		1/182 (0.5%)		4/175 (2.3%)
Cardiac disorders
Cardiovascular insufficiency	0/186 (0%)		1/182 (0.5%)		0/175 (0%)
Gastrointestinal disorders
Mouth haemorrhage	0/186 (0%)		0/182 (0%)		1/175 (0.6%)
Pancreatitis necrotising	0/186 (0%)		1/182 (0.5%)		0/175 (0%)
Peritonitis	0/186 (0%)		1/182 (0.5%)		0/175 (0%)
Hepatobiliary disorders
Cholelithiasis	0/186 (0%)		1/182 (0.5%)		0/175 (0%)
Infections and infestations
Endotoxic shock	0/186 (0%)		1/182 (0.5%)		0/175 (0%)
Pyelonephritis	0/186 (0%)		0/182 (0%)		1/175 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric neoplasm	0/186 (0%)		0/182 (0%)		1/175 (0.6%)
Nervous system disorders
Sciatica	0/186 (0%)		0/182 (0%)		1/175 (0.6%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/186 (0%)		1/182 (0.5%)		0/175 (0%)
Chronic obstructive pulmonary disease	1/186 (0.5%)		0/182 (0%)		0/175 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Solifenacin 5 mg		Solifenacin 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/186 (4.8%)		21/182 (11.5%)		34/175 (19.4%)
Gastrointestinal disorders
Dry mouth	2/186 (1.1%)		16/182 (8.8%)		30/175 (17.1%)
Constipation	7/186 (3.8%)		8/182 (4.4%)		9/175 (5.1%)

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