A Multinational Study Comparing the Long-term Efficacy and Safety of Two Medicines, Solifenacin Succinate and Mirabegron Taken Together, or Separately, in Subjects With Symptoms of Overactive Bladder

Overactive Bladder Clinical Trial

— SYNERGY II  

Official title:

A Randomized, Double-Blind, Parallel-Group, Active-Controlled, Multi-center Study to Evaluate the Long-Term Safety and Efficacy of Combination of Solifenacin Succinate With Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in Subjects With Overactive Bladder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02045862
• Other study ID #: 178-CL-102
• Secondary ID: 2012-005736-29
• Status: Completed
• Phase: Phase 3
• Start date: March 17, 2014
• Est. completion date: September 8, 2016

Study information

• Verified date: August 2018
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to examine how well the combination of two medicines (solifenacin succinate and mirabegron) worked compared to each medicine alone in the treatment of bladder problems, and how safe they were for long term use.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1829
• Est. completion date: September 8, 2016
• Est. primary completion date: September 8, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Main Inclusion at Screening (Visit 1):

• Subject had completed study 178-CL-101 or study 905-EC-012 (This inclusion criterion would no longer apply once the recruitment for study 178-CL-101 and study 905-EC-012 had been completed. In that case the subject had to have symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months);

• Subject was willing and able to complete the micturition diary and questionnaires correctly and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings;

Main Inclusion at Randomization (Visit 2):

• Subject had a micturition frequency of on average = 8 times per 24-hour period during the last 7 days of the micturition diary period (incontinence episode should not be counted as a micturition).

• Subject had experienced at least 3 incontinence episodes during the last 7 days of the micturition diary period.

• Subject had experienced on average at least 1 urgency episode (grade 3 or 4 on Patient Perception of Intensity of Urgency Scale [PPIUS]) per 24-hour period during the 7-day micturition diary period.

Exclusion Criteria:

Main Exclusion at Screening (Visit 1):

• Subject had clinically significant bladder outflow obstruction at risk of urinary retention;

• Subject had significant PVR volume (> 150 mL);

• Subject had significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor;

• Subject has an indwelling catheter or practices intermittent self-catheterization;

• Subject had evidence of a UTI (urine culture containing > 100,000 cfu/mL), chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;

• Subject had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;

Main Exclusion at Randomization (Visit 2):

• Subject had evidence of a urinary tract infection (UTI) (urine culture containing > 100,000 cfu/mL) as assessed in the Screening visit (V1) samples. The subject could be rescreened after successful treatment of the UTI (confirmed by a dipstick negative for nitrite).

• Subject had an average total daily urine volume > 3000 mL as recorded in the micturition diary period.

Related Conditions & MeSH terms

• Overactive Bladder
• Urgency Incontinence
• Urinary Bladder Diseases
• Urinary Bladder Diseases\Urologic Diseases
• Urinary Bladder Overactive
• Urinary Bladder, Overactive
• Urologic Diseases

Intervention

Drug:
• Solifenacin succinate
Participants received solifenacin 5 mg orally once a day at the same time each day.
• Mirabegron
Participants received mirabegron 50 mg orally once a day at the same time each day.
• Placebo to match solifenacin
Participants received placebo to match solifenacin 5 mg orally once a day at the same time each day. This intervention was given to maintain the blind during the study.
• Placebo to match mirabegron
Participants received placebo to match mirabegron 50 mg orally once a day at the same time each day. This intervention was given to maintain the blind during the study.

Locations

Country	Name	City	State
Australia	Site AU61022	Brisbane	Queensland
Australia	Site AU61005	Broadmeadow	New South Wales
Australia	Site AU61015	Daw Park	South Australia
Australia	Site AU61025	Footscray	Victoria
Australia	Site AU61010	Nambour	Queensland
Australia	Site AU61002	Parkville	Victoria
Australia	Site AU61004	Perth	Western Australia
Australia	Site AU61007	Randwick	New South Wales
Australia	Site AU61021	Randwick	New South Wales
Australia	Site AU61019	Sherwood	Queensland
Australia	Site AU61011	Wollongong	New South Wales
Belgium	Site BE32004	Gent
Belgium	Site BE32014	Roeselare
Belgium	Site BE32012	Sint-Truiden
Bulgaria	Site BG35908	Plovdiv
Bulgaria	Site BG35902	Ruse
Bulgaria	Site BG35903	Sofia
Bulgaria	Site BG35905	Sofia
Canada	Site CA15001	Barrie	Ontario
Canada	Site CA15006	Brampton	Ontario
Canada	Site CA15003	Brantford	Ontario
Canada	Site CA15026	Drummondville	Quebec
Canada	Site CA15035	Edmonton	Alberta
Canada	Site CA15007	Kitchener	Ontario
Canada	Site CA15039	Levis	Quebec
Canada	Site CA15020	Montreal	Quebec
Canada	Site CA15040	Montreal
Canada	Site CA15025	Quebec
Canada	Site CA15008	Saint John	New Brunswick
Canada	Site CA15027	Sherbrooke	Quebec
Canada	Site CA15004	Toronto	Ontario
Canada	Site CA15013	Toronto	Ontario
Canada	Site CA15033	Vancouver	British Columbia
Czechia	Site CZ42015	Brno
Czechia	Site CZ42001	Hradec Kralove
Czechia	Site CZ42003	Hradec Kralove
Czechia	Site CZ42010	Olomouc
Czechia	Site CZ42014	Ostrava
Czechia	Site CZ42005	Plzen
Czechia	Site CZ42008	Praha 2
Czechia	Site CZ42007	Praha 4
Czechia	Site CZ42013	Sternberk
Czechia	Site CZ42009	Uherske Hradiste
Czechia	Site CZ42006	Usti nad Labem
Denmark	Site DK45013	Aarhus
Estonia	Site EE37201	Parnu
Finland	Site FI35801	Kouvola
Germany	Site DE49008	Bad Ems
Germany	Site DE49031	Bergisch Gladbach	Northwest
Germany	Site DE49002	Duisburg
Germany	Site DE49032	Duisburg	NRW
Germany	Site DE49010	Ganderkesee
Germany	Site DE49011	Halle (Saale)
Germany	Site DE49013	Leipzig	Sachsen
Germany	Site DE49003	Lutherstadt Eisleben	Sachsen Anhalt
Germany	Site DE49034	Munich	Bavaria
Germany	Site DE49001	Neustadt I. Sachsen
Germany	Site DE49026	Rostock
Germany	Site DE49014	Sangerhausen
Hungary	Site HU36003	Csongrad	Csongrad Megye
Hungary	Site HU36007	Kecskemet	Bacs-Kiskun Megye
Hungary	Site HU36005	Pecs	Baranya Megye
Hungary	Site HU36013	Sopron	Gyor-Moson Sopron
Hungary	Site HU36001	Szentes	Csongrad Megye
Hungary	Site HU36012	Veszprem	Veszprem Megye
Italy	Site IT39022	Ancona
Italy	Site IT39007	Avellino
Italy	Site IT39001	Latina
Italy	Site IT39020	Milano
Korea, Republic of	Site KR82014	Bucheon-Si	Gyunggido
Korea, Republic of	Site KR82006	Busan
Korea, Republic of	Site KR82016	Busan
Korea, Republic of	Site KR82005	Daegu
Korea, Republic of	Site KR82029	Daegu
Korea, Republic of	Site KR82019	Daejeon
Korea, Republic of	Site KR82023	Incheon
Korea, Republic of	Site KR82010	Jeonju-si	Jeollabuk-do South Korea
Korea, Republic of	Site KR82001	Seoul
Korea, Republic of	Site KR82002	Seoul
Korea, Republic of	Site KR82003	Seoul
Korea, Republic of	Site KR82008	Seoul
Korea, Republic of	Site KR82012	Seoul	Gyunggido
Korea, Republic of	Site KR82013	Seoul
Korea, Republic of	Site KR82015	Seoul
Korea, Republic of	Site KR82017	Seoul
Korea, Republic of	Site KR82020	Seoul
Korea, Republic of	Site KR82021	Seoul
Korea, Republic of	Site KR82030	Seoul
Korea, Republic of	Site KR82004	Suwon-si	Gyeonggi-do
Latvia	Site LV37102	Liepaja
Latvia	Site LV37103	Olaine
Latvia	Site LV37105	Riga
Lithuania	Site LT37004	Kaunas
Lithuania	Site LT37008	Kaunas
Lithuania	Site LT37011	Kaunas
Lithuania	Site LT37012	Klaipeda
Lithuania	Site LT37003	Vilnius
Lithuania	Site LT37007	Vilnius
Lithuania	Site LT37009	Vilnius
Lithuania	Site LT37010	Vilnius
Malaysia	Site MY60002	Petaling Jaya
Mexico	Site MX52003	Mexico City	DF
Netherlands	Site NL31002	Amsterdam
Netherlands	Site NL31006	Enschede	NL
Netherlands	Site NL31005	Nijmegen
Netherlands	Site NL31010	Sneek
New Zealand	Site NZ64001	Christchurch	Canterbury
New Zealand	Site NZ64002	Nelson
New Zealand	Site NZ64003	Tauranga
New Zealand	Site NZ64006	Whangarei
Norway	Site NO47007	Alesund
Norway	Site NO47006	Hamar
Norway	Site NO47008	Lierskogen
Poland	Site PL48018	Bialystok
Poland	Site PL48013	Chorzow
Poland	Site PL48014	Gdynia
Poland	Site PL48004	Lodz
Poland	Site PL48010	Lublin
Poland	Site PL48011	Myslowice
Poland	Site PL48016	Opole
Poland	Site PL48005	Piaseczno
Poland	Site PL48012	Warsaw
Poland	Site PL48001	Warszawa
Poland	Site PL48003	Warszawa
Poland	Site PL48019	Wroclaw
Romania	Site RO40001	Bucuresti
Romania	Site RO40004	Bucuresti
Romania	Site RO40005	Bucuresti
Romania	Site RO40014	Cluj-Napoca	Cluj
Romania	Site RO40010	Sibiu
Romania	Site RO40002	Timisoara
Russian Federation	Site RU70015	Kazan
Russian Federation	Site RU70023	Penza
Russian Federation	Site RU70002	Saint Petersburg
Russian Federation	Site RU70019	Saint Petersburg
Russian Federation	Site RU70022	Saint Petersburg
Russian Federation	Site RU70014	St. Petersburg
Russian Federation	Site RU70018	Ufa
Singapore	Site SG65002	Singapore
Singapore	Site SG65003	Singapore
Slovakia	Site SK42105	Bratislava
Slovakia	Site SK42101	Kosice
Slovakia	Site SK42107	Kosice
Slovakia	Site SK42103	Nitra
Slovakia	Site SK42108	Poprad
Slovakia	Site SK42104	Prešov
Slovakia	Site SK42102	Trencin
Slovakia	Site SK42106	Trencin
Slovenia	Site SI38604	Murska Sobota
South Africa	Site ZA27001	Centurion	Gauteng
South Africa	Site ZA27006	Durban	Kwa Zulu Natal
South Africa	Site ZA27013	Meyerspark	Pretoria
South Africa	Site ZA27007	Paarl	Western Cape
South Africa	Site ZA27002	Roodepoort	Gauteng
Spain	Site ES34004	Madrid
Spain	Site ES34009	Madrid
Spain	Site ES34015	Madrid
Spain	Site ES34002	Valencia
Sweden	Site SE46007	Boras
Sweden	Site SE46005	Malmo
Sweden	Site SE46003	Stockholm
Sweden	Site SE46012	Stockholm
Sweden	Site SE46016	Stockholm
Sweden	Site SE46009	Uppsala
Thailand	Site TH66008	Bangkok
Thailand	Site TH66009	Khon Kaen
Ukraine	Site UA38002	Cherenigiv
Ukraine	Site UA38015	Chernivtsi
Ukraine	Site UA38013	Dnepropetrovsk
Ukraine	Site UA38007	Kiev
Ukraine	Site UA38003	Kyiv
Ukraine	Site UA38010	Kyiv
Ukraine	Site UA38008	Zaporizhzhya
United Kingdom	Site GB44006	Plymouth
United Kingdom	Site GB44001	Sheffield	South Yorkshire
United Kingdom	Site GB44009	Watford
United States	Site US10011	Albuquerque	New Mexico
United States	Site US10015	Albuquerque	New Mexico
United States	Site US10037	Alpharetta	Georgia
United States	Site US10122	Anaheim	California
United States	Site US10008	Bala-Cynwyd	Pennsylvania
United States	Site US10110	Billings	Montana
United States	Site US10282	Boston	Massachusetts
United States	Site US10060	Bradenton	Florida
United States	Site US10013	Burien	Washington
United States	Site US10104	Chandler	Arizona
United States	Site US10166	Charleston	South Carolina
United States	Site US10050	Cleveland	Ohio
United States	Site US10076	Concord	North Carolina
United States	Site US10065	Corpus Christi	Texas
United States	Site US10002	Englewood	New Jersey
United States	Site US10026	Garden City	New York
United States	Site US10558	Hanover	Maryland
United States	Site US10082	Hawaiian Gardens	California
United States	Site US10097	Hialeah	Florida
United States	Site US10148	Hialeah	Florida
United States	Site US10153	Hialeah	Florida
United States	Site US10085	Houston	Texas
United States	Site US10093	Houston	Texas
United States	Site US10219	Houston	Texas
United States	Site US10090	Hurst	Texas
United States	Site US10091	Jupiter	Florida
United States	Site US10006	Kingsport	Tennessee
United States	Site US10040	Kingston	New York
United States	Site US10088	Lake Charles	Louisiana
United States	Site US10047	Lawrenceville	New Jersey
United States	Site US10553	Lincoln	Nebraska
United States	Site US10132	Los Angeles	California
United States	Site US10133	Los Angeles	California
United States	Site US10541	Medford	Oregon
United States	Site US10154	Missoula	Montana
United States	Site US10049	Mobile	Alabama
United States	Site US10112	Mobile	Alabama
United States	Site US10079	Mount Pleasant	South Carolina
United States	Site US10004	Mountlake Terrace	Washington
United States	Site US10150	New Port Richey	Florida
United States	Site US10168	New York	New York
United States	Site US10126	Newburgh	New York
United States	Site US10109	Oklahoma City	Oklahoma
United States	Site US10124	Orlando	Florida
United States	Site US10134	Orlando	Florida
United States	Site US10149	Paramount	California
United States	Site US10009	Pembroke Pines	Florida
United States	Site US10017	Philadelphia	Pennsylvania
United States	Site US10021	Phoenix	Arizona
United States	Site US10167	Pittsburgh	Pennsylvania
United States	Site US10248	Pittsburgh	Pennsylvania
United States	Site US10250	Pittsburgh	Pennsylvania
United States	Site US10554	Plantation	Florida
United States	Site US10028	Poughkeepsie	New York
United States	Site US10129	Raleigh	North Carolina
United States	Site US10127	Roswell	Georgia
United States	Site US10105	San Antonio	Texas
United States	Site US10111	San Antonio	Texas
United States	Site US10003	San Diego	California
United States	Site US10120	Sandy Springs	Georgia
United States	Site US10155	Seattle	Washington
United States	Site US10025	Shreveport	Louisiana
United States	Site US10023	Simpsonville	South Carolina
United States	Site US10101	Summerville	South Carolina
United States	Site US10106	Tarzana	California
United States	Site US10063	Uniontown	Pennsylvania
United States	Site US10595	Valley Village	California
United States	Site US10083	Virginia Beach	Virginia
United States	Site US10067	Wadsworth	Ohio
United States	Site US10135	Walla Walla	Washington
United States	Site US10114	Watertown	Massachusetts
United States	Site US10012	West Reading	Pennsylvania
United States	Site US10053	Wheat Ridge	Colorado
United States	Site US10078	Wichita	Kansas
United States	Site US10062	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  Estonia,  Finland,  Germany,  Hungary,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Poland,  Romania,  Russian Federation,  Singapore,  Slovakia,  Slovenia,  South Africa,  Spain,  Sweden,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	A TEAE was defined as an adverse event (AE) observed after taking the first dose of double-blind treatment until 14 days after taking the last dose of double-blind treatment for non-serious AEs and until 30 days after taking the last dose of double-blind treatment for serious adverse events (SAEs). This included abnormal laboratory tests, vital signs or electrocardiogram data that were defined as AEs if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study drug or was clinically significant in the investigator's opinion. The severity of each AE was defined according to the following: Mild (No disruption of normal daily activities); Moderate (Affected normal daily activities) and Severe (Inability to perform daily activities).	From first dose of double-blind study drug up to 30 days after last dose of double-blind study drug (up to 56 weeks)
Primary	Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to the baseline and week 52 clinic visits.	Baseline and Week 52
Primary	Change From Baseline to EoT in Mean Number of Micturitions Per 24 Hours	A micturition was defined as any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7-days before the baseline and week 52 clinic visits.	Baseline and Week 52
Secondary	Change From Baseline to EoT in Mean Volume Voided Per Micturition	The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period.	Baseline and Week 52
Secondary	Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score	The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.	Baseline and Week 52
Secondary	Change From Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)	The TS-VAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement.	Baseline and Week 52
Secondary	Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes Per 24 Hours	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to the baseline and prior to each visit.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit.	Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes was the total number of times a participant records an incontinence episode during the 7-day micturition diary period prior to each visit.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Number of Incontinence-Free Days During the 7-Day Micturition Diary Period Prior to Each Visit	The number of incontinence-free days was the number of valid diary days during the 7-day micturition diary period prior to each visit with no incontinence episodes recorded.	Months 1, 3, 6, 9, 12
Secondary	Number of Incontinence-Free Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit	The number of incontinence-free days with < 8 micturitions per day was the number of valid diary days during the 7-day micturition diary period with no incontinence episodes recorded and with < 8 micturitions per day.	Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Incontinence Episodes Per 24 Hours	An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency incontinence episodes was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit	An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceeded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7-day micturition diary period prior to each visit.	Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Urgency Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit	An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The number of urgency incontinence episodes was the total number of urgency incontinence episodes recorded by the participant during the 7-day micturition diary period prior to each visit.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Micturitions Per 24 Hours	A micturition was defined as any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated from data recorded by the participant in a micturition diary for 7-days before the baseline and prior to each visit.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Number of Days With < 8 Micturitions Per Day During the 7-Day Micturition Diary Period Prior to Each Visit (at Months 1, 3, 6, 9, 12 and EoT)	The number of days with < 8 micturitions was the number of valid diary days during the 7-day micturition diary period with with less than 8 micturitions per day.	Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to EoT in Corrected Micturition Frequency	Corrected micturition frequency was defined as the mean number of micturitions per 24 hours that participants had at end of treatment if their fluid intake had remained unchanged since baseline. Corrected micturition frequency was calculated as the baseline mean volume voided per micturition multiplied by the baseline mean number of micturitions per 24 hours divided by the mean volume voided per micturition at EoT.	Baseline and Month 12
Secondary	Change From Baseline to Months 3, 6 and 12 in Mean Volume Voided Per Micturition	The mean volume voided per micturition was calculated from the data recorded by the participant during 3 consecutive days with volume measurements during the 7-day micturition diary period prior to each visit.	Baseline and Months 3, 6, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours	Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode recorded by the participant in the micturition diary for 7 days prior to each visit as 3 or 4 on the Patient Perception of Intensity of Urgency Scale (PPIUS), where 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Nocturia Episodes Per 24 Hours	A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The mean number of nocturia episodes was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit."	Baseline and Months 1, 3, 6, 9, 12
Secondary	Number of Nocturia Episodes Reported During the 7-Day Micturition Diary Period Prior to Each Visit	A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit.	Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Nocturia Episodes During the 7-Day Micturition Diary Period Prior to Each Visit	A nocturia episode was defined as waking at night 1 or more times to void (i.e., any voiding associated with sleep disturbance between the time the participant goes to bed with the intention to sleep until the time the participant gets up in the morning with the intention to stay awake). The number of nocturia episodes was the number of times a participant recorded a nocturia episode during the 7-day micturition diary period prior to each visit	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Mean Number of Pads Used Per 24 Hours	The mean number of pads used per 24 hours was calculated from data recorded by the participant in the micturition diary for 7 days prior to each visit.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit	The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.	Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Number of Pads Used During the 7-Day Micturition Diary Period Prior to Each Visit	The number of pads used was the number of times a participant recorded a new pad used during the 7-day micturition diary period prior to each visit.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9 and 12 in the OAB-q Symptom Bother Score	The OAB-q is a self-reported questionnaire with items relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Health-Related Quality of Life Questionnaire (HRQoL): Total Score	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Coping	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Concern	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQoL Subscale Score: Sleep	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consisted of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each time was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in HRQL Subscale Score: Social	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. HRQoL subscales (coping, concern, sleep and social) and total score were transformed to range from 0 (worst quality of life) to 100 (best quality of life), with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9 and 12 in the Patient's Assessment of TS-VAS	The TS-VAS is a visual analogue scale which asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) on the left to 10 (Yes, completely) on the right. A positive change from baseline indicated improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Patient Perception of Bladder Condition (PPBC)	The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants in Each Category of Patient's Global Impression of Change (PGIC) Scale: Impression in Bladder Symptoms at Month 12 and EoT	The PGIC is a 2-part questionnaire, assessing both the change in the patient's overall condition and change in bladder condition since the start of the study (from very much worse to very much improved).	Month 12
Secondary	Percentage of Participants in Each Category of PGIC Scale: Impression in General Health at Month 12 and EoT	The PGIC is a 2-part questionnaire, assessing both the change in the patient's overall condition and change in bladder condition since the start of the study (from very much worse to very much improved).	Month 12
Secondary	Number of Participants With Change From Baseline to EoT in European Quality of Llife in 5 Dimensions (EQ-5D) Questionnaire Subscale Score: Mobility	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).	Baseline and 12 Months
Secondary	Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Self-care	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).	Baseline and Month 12
Secondary	Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Usual Activities	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and has 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).	Baseline and Month 12
Secondary	Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Pain/Discomfort	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).	Baseline and Month 12
Secondary	Number of Participants With Change From Baseline to EoT in EQ-5D Questionnaire Subscale Score: Anxiety/Depression	The EQ-5D questionnaire is an international, standardized, nondisease specific instrument for describing and valuing health status, and had 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity).	Baseline and Month 12
Secondary	Change From Baseline to Months 6, 12 and EoT in Work Productivity and Activity Impairment: Specific Health Problem Questionnaire (WPAI:SHP) Score: Percent Work Time Missed	The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.	Baseline and Months 6,12
Secondary	Change From Baseline to Months 6, 12 and EoT in WPAI:SHP Score: Percent Impairment While Working	The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.	Baseline and Months 6, 12
Secondary	Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Overall Work Impairment	The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes arre expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.	Baseline and Months 6, 12
Secondary	Change From Baseline to Months 6, 12 in WPAI:SHP Score: Percent Activity Impairment	The WPAI:SHP is a self-administered questionnaire with 6 questions (Q1=Employment status; Q2=Hours absent from work due to the bladder condition; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the bladder condition on productivity while working; Q6=Impact of the bladder condition on productivity while doing regular daily activities other than work) and a 1-week recall period. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. A negative change from baseline indicated improvement.	Baseline and Months 6, 12
Secondary	Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 3 Diary Days at Months 1, 3, 6, 9, 12 and EoT	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the last 3 days of the 7-day micturition diary is reported.	Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants With = 10 Points Improvement From Baseline in the OAB-q Symptom Bother Score at Months 1, 3, 6, 9, 12 and EoT	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants With = 10 Points Improvement From Baseline in HRQoL Total Score at Months 1, 3, 6, 9, 12 and EoT	The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours at Months 1, 3, 6, 9, 12 and EoT	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants With Zero Incontinence Episodes Per 24 Hours Using the Last 7 Diary Days at Months 1, 3, 6, 9, 12 and EoT	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The percentage of participants with no incontinence episodes recorded during the 7-day micturition diary is reported.	Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants With Micturition Frequency Normalization at Months 1, 3, 6, 9, 12 and EoT	The percentage of participants with micturition frequency normalization was defined as participants who had = 8 micturitions/24 hours at baseline and < 8 micturitions/24 hours postbaseline at months 1, 3, 6, 9, 12 and EoT.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants With = 1 Point Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT	The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants With Major (= 2 Points) Improvement From Baseline in PPBC at Months 1, 3, 6, 9, 12 and EoT	The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants Who Were Double Responders (= 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q Symptom Bother Scale) at Months 1, 3, 6, 9, 12 and EoT	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The symptom bother portion consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants Who Were Double Responders (= 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 10 Points Improvement on OAB-q HRQL Total Score) at Months 1, 3, 6, 9, 12 and EoT	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The OAB-q is a self-reported questionnaire with items relating to symptom bother and HRQoL. The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants Who Were Double Responders (= 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours and at Least 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT	An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Percentage of Participants Who Were Triple Responders (= 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, = 10 Points Improvement on OAB-q Symptom Bother Scale and =1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT	The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The symptom bother portion of the OAB-q consists of 8 items, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Participants Who Were Triple Responders (= 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours, = 10 Points Improvement on OAB-q HRQL Total Score and = 1 Point Improvement on PPBC) at Months 1, 3, 6, 9, 12 and EoT	The mean number of incontinence episodes per 24 hours was calculated from data recorded by the participant in a micturition diary for 7 days prior to each visit. The HRQoL portion of the OAB-q consists of 25 HRQoL items comprising 4 HRQoL subscales, each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.The PPBC is a validated, global assessment tool using a 6-point Likert scale on which participants rated their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 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; 6. Causes me many severe problems.	Baseline and Months 1, 3, 6, 9, 12
Secondary	Change From Baseline to Months 1, 3, 6, 9, 12 and EoT in Postvoid Residual (PVR) Volume	PVR volume was assessed by ultrasonography or a bladder scanner.	Baseline and Months 1, 3, 6, 9, 12

External Links

•   Link to results on the Astellas Clinical Study Results website