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
SYNERGY II
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
2 other identifiers
interventional
1,829
30 countries
239
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2014
239 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 23, 2014
CompletedFirst Posted
Study publicly available on registry
January 27, 2014
CompletedStudy Start
First participant enrolled
March 17, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 8, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
September 8, 2016
CompletedResults Posted
Study results publicly available
June 6, 2018
CompletedOctober 31, 2024
October 1, 2024
2.5 years
January 23, 2014
May 2, 2018
October 20, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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)
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
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 Outcomes (55)
Change From Baseline to EoT in Mean Volume Voided Per Micturition
Baseline and Week 52
Change From Baseline to EoT in Overactive Bladder Questionnaire (OAB-q) Symptom Bother Score
Baseline and Week 52
Change From Baseline to EoT in the Patient's Assessment of Treatment Satisfaction-Visual Analogue Scale (TS-VAS)
Baseline and Week 52
Change From Baseline to Months 1, 3, 6, 9 and 12 in Mean Number of Incontinence Episodes Per 24 Hours
Baseline and Months 1, 3, 6, 9, 12
Number of Incontinence Episodes During the 7-Day Micturition Diary Period Prior to Each Visit
Months 1, 3, 6, 9, 12
- +50 more secondary outcomes
Study Arms (3)
Mirabegron 50 mg
ACTIVE COMPARATORParticipants received mirabegron 50 mg once a day for 52 weeks.
Solifenacin 5 mg
ACTIVE COMPARATORParticipants received solifenacin 5 mg once a day for 52 weeks.
Solifenacin 5 mg + Mirabegron 50 mg
EXPERIMENTALParticipants received solifenacin 5 mg and mirabegron 50 mg once a day for 52 weeks.
Interventions
Participants received solifenacin 5 mg orally once a day at the same time each day.
Participants received mirabegron 50 mg orally once a day at the same time each day.
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.
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.
Eligibility Criteria
You may qualify if:
- 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;
- 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.
You may not qualify if:
- 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;
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (251)
Site US10049
Mobile, Alabama, 36608, United States
Site US10112
Mobile, Alabama, 36608, United States
Site US10104
Chandler, Arizona, 85224, United States
Site US10021
Phoenix, Arizona, 85051, United States
Site US10122
Anaheim, California, 92801, United States
Site US10082
Hawaiian Gardens, California, 90716, United States
Site US10132
Los Angeles, California, 90017, United States
Site US10133
Los Angeles, California, 90036, United States
Site US10149
Paramount, California, 90723, United States
Site US10003
San Diego, California, 92120, United States
Site US10106
Tarzana, California, 91356, United States
Site US10595
Valley Village, California, 91607, United States
Site US10053
Wheat Ridge, Colorado, 80033, United States
Site US10060
Bradenton, Florida, 34208, United States
Site US10097
Hialeah, Florida, 33012, United States
Site US10148
Hialeah, Florida, 33016, United States
Site US10153
Hialeah, Florida, 33016, United States
Site US10091
Jupiter, Florida, 33458, United States
Site US10150
New Port Richey, Florida, 34652, United States
Site US10124
Orlando, Florida, 32803, United States
Site US10134
Orlando, Florida, 32806, United States
Site US10009
Pembroke Pines, Florida, 33027, United States
Site US10554
Plantation, Florida, 33317, United States
Site US10037
Alpharetta, Georgia, 30005, United States
Site US10127
Roswell, Georgia, 30076, United States
Site US10120
Sandy Springs, Georgia, 30328, United States
Site US10078
Wichita, Kansas, 67205, United States
Site US10088
Lake Charles, Louisiana, 70601, United States
Site US10025
Shreveport, Louisiana, 71106, United States
Site US10558
Hanover, Maryland, 21076, United States
Site US10282
Boston, Massachusetts, 02131, United States
Site US10114
Watertown, Massachusetts, 02472, United States
Site US10110
Billings, Montana, 59102, United States
Site US10154
Missoula, Montana, 59801, United States
Site US10553
Lincoln, Nebraska, 68510, United States
Site US10002
Englewood, New Jersey, 07631, United States
Site US10047
Lawrenceville, New Jersey, 08648, United States
Site US10011
Albuquerque, New Mexico, 87102, United States
Site US10015
Albuquerque, New Mexico, 87109, United States
Site US10026
Garden City, New York, 11530, United States
Site US10040
Kingston, New York, 12401, United States
Site US10168
New York, New York, 10065, United States
Site US10126
Newburgh, New York, 12550, United States
Site US10028
Poughkeepsie, New York, 12601, United States
Site US10076
Concord, North Carolina, 28025, United States
Site US10129
Raleigh, North Carolina, 27609, United States
Site US10062
Winston-Salem, North Carolina, 27103, United States
Site US10050
Cleveland, Ohio, 44122, United States
Site US10067
Wadsworth, Ohio, 44281, United States
Site US10109
Oklahoma City, Oklahoma, 73112, United States
Site US10541
Medford, Oregon, 97504, United States
Site US10008
Bala-Cynwyd, Pennsylvania, 19004, United States
Site US10017
Philadelphia, Pennsylvania, 19114, United States
Site US10167
Pittsburgh, Pennsylvania, 15213, United States
Site US10250
Pittsburgh, Pennsylvania, 15236, United States
Site US10248
Pittsburgh, Pennsylvania, 15243, United States
Site US10063
Uniontown, Pennsylvania, 15401, United States
Site US10012
West Reading, Pennsylvania, 19611, United States
Site US10166
Charleston, South Carolina, 29425, United States
Site US10079
Mt. Pleasant, South Carolina, 29464, United States
Site US10023
Simpsonville, South Carolina, 29681, United States
Site US10101
Summerville, South Carolina, 29485, United States
Site US10006
Kingsport, Tennessee, 37660, United States
Site US10065
Corpus Christi, Texas, 78414, United States
Site US10085
Houston, Texas, 77058, United States
Site US10219
Houston, Texas, 77094, United States
Site US10093
Houston, Texas, 77099, United States
Site US10090
Hurst, Texas, 76054, United States
Site US10105
San Antonio, Texas, 78229, United States
Site US10111
San Antonio, Texas, 78229, United States
Site US10083
Virginia Beach, Virginia, 23462, United States
Site US10013
Burien, Washington, 98166, United States
Site US10004
Mountlake Terrace, Washington, 98043, United States
Site US10155
Seattle, Washington, 98105, United States
Site US10135
Walla Walla, Washington, 99362, United States
Site AU61005
Broadmeadow, New South Wales, 2292, Australia
Site AU61007
Randwick, New South Wales, 2031, Australia
Site AU61021
Randwick, New South Wales, 2031, Australia
Site AU61011
Wollongong, New South Wales, 2522, Australia
Site AU61022
Brisbane, Queensland, 4152, Australia
Site AU61010
Nambour, Queensland, 4560, Australia
Site AU61019
Sherwood, Queensland, 4075, Australia
Site AU61015
Daw Park, South Australia, 5041, Australia
Site AU61025
Footscray, Victoria, 3011, Australia
Site AU61002
Parkville, Victoria, 3052, Australia
Site AU61004
Perth, Western Australia, 6009, Australia
Site BE32004
Ghent, 9000, Belgium
Site BE32014
Roeselare, 8800, Belgium
Site BE32012
Sint-Truiden, 3800, Belgium
Site BG35908
Plovdiv, 4003, Bulgaria
Site BG35902
Rousse, 7000, Bulgaria
Site BG35905
Sofia, 1431, Bulgaria
Site BG35903
Sofia, 1606, Bulgaria
Site CA15035
Edmonton, Alberta, T5G 0B7, Canada
Site CA15033
Vancouver, British Columbia, V5Z 4E1, Canada
Site CA15008
Saint John, New Brunswick, E2L 3J8, Canada
Site CA15001
Barrie, Ontario, L4M 7G1, Canada
Site CA15006
Brampton, Ontario, L6T 4S5, Canada
Site CA15003
Brantford, Ontario, N3S 6T6, Canada
Site CA15007
Kitchener, Ontario, N2N 2B9, Canada
Site CA15013
Toronto, Ontario, M4N 3M5, Canada
Site CA15004
Toronto, Ontario, M4S 1Y2, Canada
Site CA15026
Drummondville, Quebec, J2B 7T1, Canada
Site CA15039
Lévis, Quebec, G6W 5M6, Canada
Site CA15020
Montreal, Quebec, H4N 3C5, Canada
Site CA15025
Québec, Quebec, G1S 2L6, Canada
Site CA15027
Sherbrooke, Quebec, J1H 1Z1, Canada
Site CA15040
Montreal, H2R 1V6, Canada
Site CZ42015
Brno, 602 00, Czechia
Site CZ42003
Hradec Králové, 500 02, Czechia
Site CZ42001
Hradec Králové, 50005, Czechia
Site CZ42010
Olomouc, 772 00, Czechia
Site CZ42014
Ostrava, 700 30, Czechia
Site CZ42005
Pilsen, 32600, Czechia
Site CZ42008
Prague, 12808, Czechia
Site CZ42007
Prague, 140 00, Czechia
Site CZ42013
Sternberk, 78501, Czechia
Site CZ42009
Uherské Hradiště, 686 08, Czechia
Site CZ42006
Ústí nad Labem, 40001, Czechia
Site DK45013
Aarhus, 8200, Denmark
Site EE37201
Pärnu, 80010, Estonia
Site FI35801
Kouvola, 45200, Finland
Site DE49034
Munich, Bavaria, 81377, Germany
Site DE49032
Duisburg, North Rhine-Westphalia, 47179, Germany
Site DE49031
Bergisch Gladbach, Northwest, 51427, Germany
Site DE49013
Leipzig, Saxony, 04105, Germany
Site DE49003
Eisleben Lutherstadt, Saxony-Anhalt, 06295, Germany
Site DE49008
Bad Ems, 56130, Germany
Site DE49002
Duisburg, 47051, Germany
Site DE49010
Ganderkesee, 27777, Germany
Site DE49011
Halle, 06132, Germany
Site DE49001
Neustadt in Sachsen, 01844, Germany
Site DE49026
Rostock, 18107, Germany
Site DE49014
Sangerhausen, 06526, Germany
Site HU36007
Kecskemét, Bacs-Kiskun Megye, 6000, Hungary
Site HU36005
Pécs, Baranya, 7621, Hungary
Site HU36003
Csongrád, Csongrád megye, 6640, Hungary
Site HU36001
Szentes, Csongrád megye, 6600, Hungary
Site HU36013
Sopron, Győr-Moson-Sopron, 9400, Hungary
Site HU36012
Veszprém, Veszprém megye, 8200, Hungary
Site IT39022
Ancona, 60126, Italy
Site IT39007
Avellino, 83100, Italy
Site IT39001
Latina, 04100, Italy
Site IT39020
Milan, 20100, Italy
Site LV37102
Liepāja, LV-3401, Latvia
Site LV37103
Olaine, LV-2114, Latvia
Site LV37105
Riga, LV-1002, Latvia
Site LT37008
Kaunas, 47144, Lithuania
Site LT37004
Kaunas, 50009, Lithuania
Site LT37011
Kaunas, LT49449, Lithuania
Site LT37012
Klaipėda, LT-92288, Lithuania
Site LT37010
Vilnius, 10207, Lithuania
Site LT37003
Vilnius, LT-01118, Lithuania
Site LT37007
Vilnius, LT-08661, Lithuania
Site LT37009
Vilnius, LT-09108, Lithuania
Site MY60002
Petaling Jaya, 47500, Malaysia
Site MX52003
Mexico City, Mexico City, 06700, Mexico
Site NL31006
Enschede, NL, 7513ER, Netherlands
Site NL31002
Amsterdam, 1105 AZ, Netherlands
Site NL31005
Nijmegen, 6532 SZ, Netherlands
Site NL31010
Sneek, 8601 ZK, Netherlands
Site NZ64001
Christchurch, Canterbury, 8013, New Zealand
Site NZ64002
Nelson, 7010, New Zealand
Site NZ64003
Tauranga, 3140, New Zealand
Site NZ64006
Whangarei, 0112, New Zealand
Site NO47007
Ålesund, 6003, Norway
Site NO47006
Hamar, 2317, Norway
Site NO47008
Lierskogen, 3420, Norway
Site PL48018
Bialystok, 15-351, Poland
Site PL48013
Chorzów, 41-500, Poland
Site PL48014
Gdynia, 81-384, Poland
Site PL48004
Lodz, 90-302, Poland
Site PL48010
Lublin, 20-632, Poland
Site PL48011
Mysłowice, 41-400, Poland
Site PL48016
Opole, 45-086, Poland
Site PL48005
Piaseczno, 05-500, Poland
Site PL48012
Warsaw, 00-909, Poland
Site PL48003
Warsaw, 02-507, Poland
Site PL48001
Warsaw, 02-929, Poland
Site PL48019
Wroclaw, 50-088, Poland
Site RO40014
Cluj-Napoca, Cluj, 400046, Romania
Site RO40004
Bucharest, 042122, Romania
Site RO40001
Bucharest, 50659, Romania
Site RO40005
Bucharest, 50659, Romania
Site RO40010
Sibiu, 550245, Romania
Site RO40002
Timișoara, 300736, Romania
Site RU70015
Kazan', 420097, Russia
Site RU70023
Penza, 440026, Russia
Site RU70019
Saint Petersburg, 194354, Russia
Site RU70002
Saint Petersburg, 197089, Russia
Site RU70022
Saint Petersburg, 198103, Russia
Site RU70014
Saint Petersburg, 199178, Russia
Site RU70018
Ufa, 450096, Russia
Site SG65002
Singapore, 169608, Singapore
Site SG65003
Singapore, 229899, Singapore
Site SK42105
Bratislava, 82101, Slovakia
Site SK42107
Košice, 04001, Slovakia
Site SK42101
Košice, 04013, Slovakia
Site SK42103
Nitra, 949 01, Slovakia
Site SK42108
Poprad, 05801, Slovakia
Site SK42104
Prešov, 080 01, Slovakia
Site SK42102
Trenčín, 91101, Slovakia
Site SK42106
Trenčín, 91101, Slovakia
Site SI38604
Murska Sobota, 9000, Slovenia
Site ZA27001
Centurion, Gauteng, 0157, South Africa
Site ZA27002
Roodepoort, Gauteng, 1709, South Africa
Site ZA27006
Durban, KwaZulu-Natal, 4001, South Africa
Site ZA27013
Meyerspark, Pretoria, 0184, South Africa
Site ZA27007
Paarl, Western Cape, 7646, South Africa
Site KR82004
Suwon, Gyeonggi-do, 443-721, South Korea
Site KR82014
Bucheon-si, Gyunggido, 420-767, South Korea
Site KR82012
Seoul, Gyunggido, 143-729, South Korea
Site KR82010
Jeonju, Jeollabuk-do South Korea, 561-712, South Korea
Site KR82006
Busan, 602-715, South Korea
Site KR82016
Busan, 602-739, South Korea
Site KR82005
Daegu, 705-717, South Korea
Site KR82029
Daegu, 705-718, South Korea
Site KR82019
Daejeon, 301-721, South Korea
Site KR82023
Incheon, 405760, South Korea
Site KR82003
Seoul, 05505, South Korea
Site KR82021
Seoul, 100-380, South Korea
Site KR82020
Seoul, 110-744, South Korea
Site KR82030
Seoul, 120-752, South Korea
Site KR82013
Seoul, 134-701, South Korea
Site KR82017
Seoul, 134-872, South Korea
Site KR82002
Seoul, 135-710, South Korea
Site KR82008
Seoul, 135-720, South Korea
Site KR82015
Seoul, 136-075, South Korea
Site KR82001
Seoul, 137-701, South Korea
Site ES34004
Madrid, 28031, Spain
Site ES34015
Madrid, 28044, Spain
Site ES34009
Madrid, 28046, Spain
Site ES34002
Valencia, 46026, Spain
Site SE46007
Borås, 506 30, Sweden
Site SE46005
Malmo, 211 52, Sweden
Site SE46016
Stockholm, 111 57, Sweden
Site SE46012
Stockholm, 141 86, Sweden
Site SE46003
Stockholm, 182 88, Sweden
Site SE46009
Uppsala, 753 19, Sweden
Site TH66008
Bangkok, 10400, Thailand
Site TH66009
Khon Kaen, 40002, Thailand
Site UA38002
Cherenigiv, 14034, Ukraine
Site UA38015
Chernivtsi, 58002, Ukraine
Site UA38013
Dnipro, 49005, Ukraine
Site UA38007
Kiev, 02232, Ukraine
Site UA38003
Kyiv, 02660, Ukraine
Site UA38010
Kyiv, 04053, Ukraine
Site UA38008
Zaporizhzhya, 69600, Ukraine
Site GB44001
Sheffield, South Yorkshire, S10 2JF, United Kingdom
Site GB44006
Plymouth, PL6 8DH, United Kingdom
Site GB44009
Watford, WD25 7NL, United Kingdom
Related Publications (1)
Gratzke C, van Maanen R, Chapple C, Abrams P, Herschorn S, Robinson D, Ridder A, Stoelzel M, Paireddy A, Yoon SJ, Al-Shukri S, Rechberger T, Mueller ER. Long-term Safety and Efficacy of Mirabegron and Solifenacin in Combination Compared with Monotherapy in Patients with Overactive Bladder: A Randomised, Multicentre Phase 3 Study (SYNERGY II). Eur Urol. 2018 Oct;74(4):501-509. doi: 10.1016/j.eururo.2018.05.005. Epub 2018 Jun 1.
PMID: 29866467DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Due to lack of data integrity, one site's data were not included in the efficacy and safety analysis, and another site's data for 5 patients were not included in the efficacy analysis.
Results Point of Contact
- Title
- Clinical Trial Disclosure
- Organization
- Astellas Pharma Europe B.V.
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Europe B.V.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 23, 2014
First Posted
January 27, 2014
Study Start
March 17, 2014
Primary Completion
September 8, 2016
Study Completion
September 8, 2016
Last Updated
October 31, 2024
Results First Posted
June 6, 2018
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.