Clinical trial NCT01908829: A Trial Comparing Combination Treatment (Solifenacin Plus Mirabegron) With One Treatment Alone (Solifenacin)
Official title: A Randomized, Double-Blind, Multi-Centre Study to Evaluate the Efficacy and Safety of Adding Mirabegron to Solifenacin in Incontinent OAB Subjects Who Have Received Solifenacin for 4 Weeks and Warrant Additional Relief for Their OAB Symptoms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urinary Bladder Diseases
Urinary Bladder Overactive
Urologic Diseases
Keywords: Vesitrim
Betanis
Urgency
Frequency
Mirabegron
YM178
Betmiga
Vesicare
Micturition
YM905
Solifenacin
Urinary incontinence
Overactive Bladder (OAB)
Myrbetriq
Vesikur
Urgency incontinence
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2013-07-26
Enrollment: 2174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to see if adding a new type of medication recently approved to treat overactive bladder (mirabegron) to an antimuscarinic treatment (solifenacin) would be more effective in controlling incontinence than when using the antimuscarinic treatment alone.


Eligibility criteria: Inclusion Criteria:

* Main Inclusion at Screening:

  1. Subject has symptoms of OAB (urinary frequency and urgency with urgency incontinence) for \>= 3 months prior to the screening visit
  2. Subject is willing and able to complete the micturition diary and questionnaires correctly, including collection and measurement of urine output for 3 days prior to each visit;
  3. Subject has symptoms of "wet" OAB (urinary frequency and urgency with incontinence or mixed incontinence with predominant urgency incontinence), and reports an average of at least 2 incontinence episodes per day.
* Main Inclusion at Run-in (Visit 2):

  1. Subject experiences on average at least 1 episode of urgency (grade 3 or 4) with or without incontinence per 24-hour period during the 3-day micturition diary period.
  2. Subject experiences on average at least 2 incontinence episodes per 24-hour period during the 3-day micturition diary period.
  3. Subject experiences on average at least 8 micturitions (excluding incontinence episodes) per 24-hour period during the 3-day micturition diary period.
* Main Inclusion at Randomization (Visit 3):

  1. Subject experiences at least 1 incontinence episode during the 3-day micturition diary period and wishes to increase their treatment for OAB symptoms.

Exclusion Criteria:

* Main Exclusion at Screening:

  1. Subject in the opinion of the investigator has clinically significant Bladder Outlet Obstruction (BOO).
  2. Subject has significant Post-void residual (PVR) volume (PVR \> 150 ml).
  3. Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator
  4. Subject has an indwelling catheter or practices intermittent self catheterization.
  5. Subject has evidence of a UTI.
  6. Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs
  7. Subject has moderate to severe hepatic impairment
  8. Subject has severe renal impairment or End Stage Renal disease
  9. Subject has a clinically significant abnormal Electrocardiogram (ECG)
  10. Subject has a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
  11. Subject has a QTcF interval \> 450 ms for males or \> 470 ms for females or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia).
  12. Subject has received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
  13. Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
* Main Exclusion at Randomization (visit 3):

  1. Subject has achieved 100% continence from Visit 2 to Visit 3 (no incontinence episodes are recorded in the 3 day diary administered for 3 days prior to Visit 3).
  2. Subject does not desire an increase in study medication.
  3. Subject has an average total daily urine volume \> 3000ml as recorded in the micturition diary.
  4. Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.
  5. Subject has a clinically significant abnormal ECG

Primary outcomes:
measure: Change From Baseline to End of Treatment (EoT) in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and end of treatment (up to 12 weeks)
Secondary outcomes:
measure: Change From Baseline to Weeks 4, 8 & 12 in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and weeks 4, 8 & 12
measure: Number of Incontinence Episodes Reported During the 3-Day Diary
timeFrame: Weeks 4, 8 and 12
measure: Change From Baseline in Mean Volume Voided (MVV) Per Micturition
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline to EoT in Corrected Micturition Frequency (CMF)
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline in Mean Number of Urgency Incontinence (UI) Episodes Per 24 Hours
timeFrame: Baseline and weeks 4, 8 & 12
measure: Number of UI Episodes Reported During the 3-Day Diary
timeFrame: Weeks 4, 8 and 12
measure: Change From Baseline in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in Mean Number of Pads Per 24 Hours
timeFrame: Baseline and weeks 4, 8 & 12
measure: Number of Pads Used During the 3-Day Diary
timeFrame: Weeks 4, 8 and 12
measure: Change From Baseline in Mean Number of Nocturia Episodes
timeFrame: Baseline and weeks 4, 8 & 12
measure: Number of Nocturia Episodes Reported Over 3-Day Diary
timeFrame: Weeks 4, 8 and 12
measure: Number of Participants With Change From Baseline to EoT in Euroqol European Quality of Life-5 Dimensions (EQ-5D) Subscale Score: Mobility
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Self-care
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Usual Activities
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Pain/Discomfort
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Number of Participants With Change From Baseline to EoT in EQ-5D Subscale Score: Anxiety/Depression
timeFrame: Baseline and EoT (up to 12 weeks)
measure: Change From Baseline in Overactive Bladder Symptom (OAB-q) Symptom Bother Score
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in OAB-q Health-Related Quality of Life (HRQL) Total Score
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in OAB-q HRQL Subscale Score: Coping
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in OAB-q HRQL Subscale Score: Concern
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in OAB-q HRQL Subscale Score: Sleep
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in OAB-q HRQL Subscale Score: Social Interaction
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in Treatment Satisfaction - Visual Analogue Scale (TS-VAS) Score
timeFrame: Baseline and weeks 4, 8 & 12
measure: Change From Baseline in Patient Perception Bladder Control (PPBC) Score
timeFrame: Baseline and weeks 4, 8 & 12
measure: Number of Participants in Each Category of Patient and Clinician Global Impression of Change Scales (PGIC and CGIC)
timeFrame: End of treatment (up to 12 weeks)
measure: Percentage of Participants With at Least a 50% Decrease From Baseline in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With Zero Incontinence Episodes Postbaseline
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With a Mean of at Least 8 Micturitions Per 24 Hours at Baseline and Less Than 8 Micturitions Per 24 Hours Postbaseline
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With at Least a 10-Point Improvement From Baseline in OAB-q Symptom Bother Score
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With at Least a 10-Point Improvement From Baseline in HRQL Total Score
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With at Least a 1-Point Improvement From Baseline in PPBC
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With Major (at Least 2-Point) Improvement From Baseline in PPBC
timeFrame: Weeks 4, 8 and 12
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose of double blind treatment until 30 days after last dose (up to 16 weeks)
measure: Change From Baseline in Post Void Residual (PVR) Volume
timeFrame: Baseline and weeks 4, 8 & 12
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Genova Clinical Research
state: Arizona
city: Buena Park
country: United States
facility: Associated Pharmaceutical Research Center, Inc.
state: California
city: Los Angeles
country: United States
facility: The American Institute of Research
state: California
city: Valley Village
country: United States
facility: Bayview Research Group
state: California
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Clearwater
country: United States
facility: Innovative Research of West FL
state: Florida
city: Hialeah
country: United States
facility: Best Quality Research Inc.
state: Florida
city: Hialeah
country: United States
facility: Palmetto Professional Research
state: Florida
city: Kissimmee
country: United States
facility: Urology Center of Central Florida
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: West Palm Beach
country: United States
facility: Private Practice
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research, LLC
state: Georgia
city: Suwanee
country: United States
facility: Herman Clinical Research
state: Georgia
city: Coeur d'Alene
country: United States
facility: North Idaho Urology
state: Idaho
city: Jeffersonville
country: United States
facility: First Urology, PSC
state: Indiana
city: Newburgh
country: United States
facility: Deaconess Gateway Health Center
state: Indiana
city: Hyattsville
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Watertown
country: United States
facility: Bay State Clinical Trials, Inc.
state: Massachusetts
city: Kalamazoo
country: United States
facility: Beyer Research
state: Michigan
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Brooklyn
country: United States
facility: Brooklyn Urology Research Group
state: New York
city: Garden City
country: United States
facility: Advanced Urology Centers of New York
state: New York
city: Kingston
country: United States
facility: Premier Medical Group of the Hudson Valley PC
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley PC
state: New York
city: Cary
country: United States
facility: PMG Research of Raleigh, dba PMG Research of Cary
state: North Carolina
city: Greensboro
country: United States
facility: Alliance Urology Specialists
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Dayton
country: United States
facility: Providence Health Partners
state: Ohio
city: Jenkintown
country: United States
facility: The Clinical Trial Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Salt Lake City
country: United States
facility: Jean Brown Research
state: Utah
city: Alexandria
country: United States
facility: Alexandria Clinical Research
state: Virginia
city: Yerevan
country: Armenia
facility: Site: 37402
city: Yerevan
country: Armenia
facility: Site: 37403
city: Yerevan
country: Armenia
facility: Site: 37405
city: Adelaide
country: Australia
facility: Site: 61006
city: Kogarah, Sydney
country: Australia
facility: Site: 61001
city: Victoria
country: Australia
facility: Site: 61016
city: Graz
country: Austria
facility: Site: 43008
city: Innsbruck
country: Austria
facility: Site: 43001
city: Innsbruck
country: Austria
facility: Site: 43006
city: Linz
country: Austria
facility: Site: 43007
city: Vienna
country: Austria
facility: Site: 43002
city: Vienna
country: Austria
facility: Site: 43004
city: Vienna
country: Austria
facility: Site: 43005
city: Vienna
country: Austria
facility: Site: 43010
city: Vienna
country: Austria
facility: Site: 43011
city: Vienna
country: Austria
facility: Site: 43012
city: Wels
country: Austria
facility: Site: 43003
city: Anderlecht
country: Belgium
facility: Site: 32007
city: Deurne
country: Belgium
facility: Site: 32013
city: Edegem
country: Belgium
facility: Site: 32009
city: Gent
country: Belgium
facility: Site: 32003
city: Gent
country: Belgium
facility: Site: 32005
city: Kortrijk
country: Belgium
facility: Site: 32015
city: Liege
country: Belgium
facility: Site: 32008
city: Roeselare
country: Belgium
facility: Site: 32014
city: Barrie
country: Canada
facility: Site: 15001
city: Bathurst
country: Canada
facility: Site: 15009
city: Brampton
country: Canada
facility: Site: 15006
city: Granby
country: Canada
facility: Site: 15015
city: Kelowna
country: Canada
facility: Site: 15014
city: Kitchener
country: Canada
facility: Site: 15007
city: Sherbrooke
country: Canada
facility: Site: 15019
city: Toronto
country: Canada
facility: Site: 15012
city: Toronto
country: Canada
facility: Site: 15013
city: Victoriaville
country: Canada
facility: Site: 15018
city: Victoria
country: Canada
facility: Site: 15016
city: Victoria
country: Canada
facility: Site: 15047
city: Brno
country: Czechia
facility: Site: 42015
city: Melnik
country: Czechia
facility: Site: 42020
city: Nachod
country: Czechia
facility: Site: 42018
city: Plzen
country: Czechia
facility: Site: 42004
city: Plzen
country: Czechia
facility: Site: 42021
city: Prague 1
country: Czechia
facility: Site: 42016
city: Prague
country: Czechia
facility: Site: 42008
city: Praha 2
country: Czechia
facility: Site: 42017
city: Praha 4
country: Czechia
facility: Site: 42007
city: Praha 4
country: Czechia
facility: Site: 42022
city: Aarhus N
country: Denmark
facility: Site: 45008
city: Frederiksberg
country: Denmark
facility: Site: 45003
city: Herlev
country: Denmark
facility: Site: 45009
city: Odense C
country: Denmark
facility: Site: 45011
city: Helsinki (hus)
country: Finland
facility: Site: 35804
city: Tampere
country: Finland
facility: Site: 35805
city: Bordeaux Cedex
country: France
facility: Site: 33018
city: Marseille
country: France
facility: Site: 33017
city: T'bilisi
country: Georgia
facility: Site: 99502
city: Bad Ems
country: Germany
facility: Site: 49008
city: Berlin
country: Germany
facility: Site: 49022
city: Hagenow
country: Germany
facility: Site: 49021
city: Halle (Saale)
country: Germany
facility: Site: 49011
city: Hamburg
country: Germany
facility: Site: 49004
city: Henningsdorf
country: Germany
facility: Site: 49018
city: Hettstedt
country: Germany
facility: Site: 49009
city: Koblenz
country: Germany
facility: Site: 49017
city: Lutherstadt Eisleben
country: Germany
facility: Site: 49003
city: Reutlingen
country: Germany
facility: Site: 49020
city: Sangerhausen
country: Germany
facility: Site: 49014
city: Athens
country: Greece
facility: Site: 30001
city: Heraklion, Crete
country: Greece
facility: Site: 30005
city: Patras
country: Greece
facility: Site: 30002
city: Csongrad
country: Hungary
facility: Site: 36003
city: Hajduszoboszlo
country: Hungary
facility: Site: 36011
city: Nyiregyhaza
country: Hungary
facility: Site: 36002
city: Salgotarjan
country: Hungary
facility: Site: 36008
city: Szekszard
country: Hungary
facility: Site: 36009
city: Cork
country: Ireland
facility: Site: 35303
city: Dublin
country: Ireland
facility: Site: 35301
city: Dublin
country: Ireland
facility: Site: 35309
city: Dublin
country: Ireland
facility: Site: 35310
city: Limerick
country: Ireland
facility: Site: 35306
city: Mullingar
country: Ireland
facility: Site: 35313
city: Tralee
country: Ireland
facility: Site: 35304
city: Waterford
country: Ireland
facility: Site: 35305
city: Haifa
country: Israel
facility: Site: 97201
city: Jerusalem
country: Israel
facility: Site: 97202
city: Kfar Saba
country: Israel
facility: Site: 97207
city: Petach Tikva
country: Israel
facility: Site: 97203
city: Petach Tikva
country: Israel
facility: Site: 97205
city: Tel Hashomer
country: Israel
facility: Site: 97206
city: Avellino
country: Italy
facility: Site: 39007
city: Cantanzaro
country: Italy
facility: Site: 39002
city: Firenze
country: Italy
facility: Site: 39010
city: Perugia
country: Italy
facility: Site: 39006
city: Treviglio (BG)
country: Italy
facility: Site: 39013
city: Varese
country: Italy
facility: Site: 39009
city: Beirut
country: Lebanon
facility: Site: 96101
city: Amsterdam
country: Netherlands
facility: Site: 31008
city: Bekkestua
country: Norway
facility: Site: 47005
city: Tonsberg
country: Norway
facility: Site: 47002
city: Trondheim
country: Norway
facility: Site: 47003
city: Kolbuszowa Dolna
country: Poland
facility: Site: 48002
city: Krakow
country: Poland
facility: Site: 48006
city: Lublin
country: Poland
facility: Site: 48010
city: Piaseczno
country: Poland
facility: Site: 48005
city: Warszawa
country: Poland
facility: Site: 48001
city: Warszawa
country: Poland
facility: Site: 48008
city: Lisbon
country: Portugal
facility: Site: 35104
city: Lisbon
country: Portugal
facility: Site: 35105
city: Matosinhos
country: Portugal
facility: Site: 35102
city: Porto
country: Portugal
facility: Site: 35103
city: Setubal
country: Portugal
facility: Site: 35101
city: Tomar
country: Portugal
facility: Site: 35106
city: Bucharest
country: Romania
facility: Site: 40016
city: Bucharest
country: Romania
facility: Site: 40018
city: Craiova
country: Romania
facility: Site: 40012
city: Craiova
country: Romania
facility: Site: 40019
city: Judetul Ilfov
country: Romania
facility: Site: 40003
city: Oradea
country: Romania
facility: Site: 40017
city: Timisoara
country: Romania
facility: Site: 40020
city: Moscow
country: Russian Federation
facility: Site: 70003
city: Moscow
country: Russian Federation
facility: Site: 70004
city: Moscow
country: Russian Federation
facility: Site: 70005
city: Moscow
country: Russian Federation
facility: Site: 70008
city: Moscow
country: Russian Federation
facility: Site: 70010
city: Moscow
country: Russian Federation
facility: Site: 70011
city: Moscow
country: Russian Federation
facility: Site: 70012
city: Moscow
country: Russian Federation
facility: Site: 70024
city: Rostove-on-Don
country: Russian Federation
facility: Site: 70013
city: Saint Petersburg
country: Russian Federation
facility: Site: 70002
city: Saint Petersburg
country: Russian Federation
facility: Site: 70006
city: Saint Petersburg
country: Russian Federation
facility: Site: 70007
city: Saint Petersburg
country: Russian Federation
facility: Site: 70009
city: Saratov
country: Russian Federation
facility: Site: 70025
city: Bratislava
country: Slovakia
facility: Site: 42110
city: Kosice
country: Slovakia
facility: Site: 42114
city: Michalovce
country: Slovakia
facility: Site: 42113
city: Nove Zamky
country: Slovakia
facility: Site: 42111
city: Piestany
country: Slovakia
facility: Site: 42112
city: Poprad
country: Slovakia
facility: Site: 42108
city: Zilina
country: Slovakia
facility: Site: 42109
city: Ljubljana
country: Slovenia
facility: Site: 38601
city: Maribor
country: Slovenia
facility: Site: 38606
city: Maribor
country: Slovenia
facility: Site: 38607
city: Ptuj
country: Slovenia
facility: Site: 38610
city: Barcelona
country: Spain
facility: Site: 34012
city: Bilbao
country: Spain
facility: Site: 34016
city: Getafe (Madrid)
country: Spain
facility: Site: 34001
city: Madrid
country: Spain
facility: Site: 34004
city: Madrid
country: Spain
facility: Site: 34015
city: Mendaro
country: Spain
facility: Site: 34023
city: Miranda de Ebro
country: Spain
facility: Site: 34021
city: San Sebastian de los Reyes
country: Spain
facility: Site: 34018
city: San Sebastian
country: Spain
facility: Site: 34013
city: Sevilla
country: Spain
facility: Site: 34007
city: Sevilla
country: Spain
facility: Site: 34020
city: Vigo
country: Spain
facility: Site: 34014
city: Halmstad
country: Sweden
facility: Site: 46004
city: Lund
country: Sweden
facility: Site: 46013
city: Norrtalje
country: Sweden
facility: Site: 46014
city: Stockholm
country: Sweden
facility: Site: 46001
city: Stockholm
country: Sweden
facility: Site: 46012
city: Umea
country: Sweden
facility: Site: 46015
city: Baden
country: Switzerland
facility: Site: 41008
city: Frauenfeld
country: Switzerland
facility: Site: 41001
city: Ankara
country: Turkey
facility: Site: 90005
city: Ankara
country: Turkey
facility: Site: 90008
city: Izmir
country: Turkey
facility: Site: 90002
city: Izmir
country: Turkey
facility: Site: 90003
city: Kocaeli
country: Turkey
facility: Site: 90007
city: Manisa
country: Turkey
facility: Site: 90004
city: Sivas
country: Turkey
facility: Site: 90006
city: Bristol
country: United Kingdom
facility: Site: 44007
city: Cambridge
country: United Kingdom
facility: Site: 44012
city: Cheltenham
country: United Kingdom
facility: Site: 44015
city: Coventry
country: United Kingdom
facility: Site: 44019
city: Garston
country: United Kingdom
facility: Site: 44009
city: Kings Lynn
country: United Kingdom
facility: Site: 44016
city: London
country: United Kingdom
facility: Site: 44017
city: Northampton
country: United Kingdom
facility: Site: 44018
city: Nottingham
country: United Kingdom
facility: Site: 44010
city: Plymouth
country: United Kingdom
facility: Site: 44008
city: Taunton
country: United Kingdom
facility: Site: 44013
city: West Yorkshire
country: United Kingdom
facility: Site: 44011
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Clinical Study Manager
role: STUDY_DIRECTOR
References:
citation: Gibson W, MacDiarmid S, Huang M, Siddiqui E, Stolzel M, Choudhury N, Drake MJ. Treating Overactive Bladder in Older Patients with a Combination of Mirabegron and Solifenacin: A Prespecified Analysis from the BESIDE Study. Eur Urol Focus. 2017 Dec;3(6):629-638. doi: 10.1016/j.euf.2017.08.008. Epub 2017 Sep 12.
citation: Drake MJ, Chapple C, Esen AA, Athanasiou S, Cambronero J, Mitcheson D, Herschorn S, Saleem T, Huang M, Siddiqui E, Stolzel M, Herholdt C, MacDiarmid S; BESIDE study investigators. Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE). Eur Urol. 2016 Jul;70(1):136-145. doi: 10.1016/j.eururo.2016.02.030. Epub 2016 Mar 8.