A Study to Evaluate the Efficacy, Safety and Tolerability of Mirabegron and Solifenacin Succinate Alone and in Combination for the Treatment of Overactive Bladder

NCT ID: NCT01340027

Last Updated: 2024-10-31

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

1307 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-29

Study Completion Date

2012-06-28

Brief Summary

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The purpose of this study is to examine how well two medicines in combination (solifenacin succinate and mirabegron) work in the treatment of bladder problems over a 12-week period.

Detailed Description

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Conditions

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Urologic Diseases Urinary Bladder Diseases Urological Manifestations Signs and Symptoms Urinary Bladder, Overactive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Placebo

Participants received matching placebo tablets orally once a day for 12 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

oral

Mirabegron 25 mg

Participants received mirabegron 25 mg tablets orally once a day for 12 weeks

Group Type ACTIVE_COMPARATOR

Mirabegron

Intervention Type DRUG

oral

Mirabegron 50 mg

Participants received mirabegron 50 mg tablets orally once a day for 12 weeks

Group Type ACTIVE_COMPARATOR

Mirabegron

Intervention Type DRUG

oral

Solifenacin 2.5 mg

Participants received solifenacin 2.5 mg tablets orally once a day for 12 weeks

Group Type ACTIVE_COMPARATOR

Solifenacin succinate

Intervention Type DRUG

oral

Solifenacin 5 mg

Participants received solifenacin 5 mg tablets orally once a day for 12 weeks

Group Type ACTIVE_COMPARATOR

Solifenacin succinate

Intervention Type DRUG

oral

Solifenacin 10 mg

Participants received solifenacin 10 mg tablets orally once a day for 12 weeks

Group Type ACTIVE_COMPARATOR

Solifenacin succinate

Intervention Type DRUG

oral

Solifenacin 2.5 mg and Mirabegron 25 mg

Participants received solifenacin 2.5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks

Group Type EXPERIMENTAL

Mirabegron

Intervention Type DRUG

oral

Solifenacin succinate

Intervention Type DRUG

oral

Solifenacin 2.5 mg and Mirabegron 50 mg

Participants received solifenacin 2.5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks

Group Type EXPERIMENTAL

Mirabegron

Intervention Type DRUG

oral

Solifenacin succinate

Intervention Type DRUG

oral

Solifenacin 5 mg and Mirabegron 25 mg

Participants received solifenacin 5 mg and mirabegron 25 mg tablets orally once a day for 12 weeks

Group Type EXPERIMENTAL

Mirabegron

Intervention Type DRUG

oral

Solifenacin succinate

Intervention Type DRUG

oral

Solifenacin 5 mg and Mirabegron 50 mg

Participants received solifenacin 5 mg and mirabegron 50 mg tablets orally once a day for 12 weeks

Group Type EXPERIMENTAL

Mirabegron

Intervention Type DRUG

oral

Solifenacin succinate

Intervention Type DRUG

oral

Solifenacin 10 mg and Mirabegron 25 mg

Participants received solifenacin 10 mg and mirabegron 25 mg tablets orally once a day for 12 weeks

Group Type EXPERIMENTAL

Mirabegron

Intervention Type DRUG

oral

Solifenacin succinate

Intervention Type DRUG

oral

Solifenacin 10 mg and Mirabegron 50 mg

Participants received solifenacin 10 mg and mirabegron 50 mg tablets orally once a day for 12 weeks

Group Type EXPERIMENTAL

Mirabegron

Intervention Type DRUG

oral

Solifenacin succinate

Intervention Type DRUG

oral

Interventions

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Mirabegron

oral

Intervention Type DRUG

Solifenacin succinate

oral

Intervention Type DRUG

Placebo

oral

Intervention Type DRUG

Other Intervention Names

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Betmiga Myrbetric Myrbetriq Betanis YM178 Vesikur Vesicare

Eligibility Criteria

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Inclusion Criteria

* Subject has a Body Mass Index (BMI) of between 18 and 35 kg/m\^2 and a total body weight between 50 and 95 kg;
* Subject is willing and able to complete the micturition diary and questionnaires correctly and is willing 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 has symptoms of overactive bladder (OAB; urinary frequency, urgency and/or urgency incontinence) for at least 3 months.

* Subject has experienced frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period (incontinence episode should not be counted as a micturition);
* Subject must experience at least 1 episode of urgency (grade 3 or 4) per 24-hour period (with or without urgency incontinence) during the 3 day micturition diary period.

Exclusion Criteria

* Subject is breastfeeding, pregnant or intends to become pregnant during the study. The pregnancy test (Beta Human Chorionic Gonadotropin in serum) at Screening must be negative in women of childbearing potential;
* Female subjects of childbearing potential and not using a highly effective method of birth control during the study and for 30 days after final study drug administration.
* Male subjects (unless surgically sterile) with female spouses/partners who are of childbearing potential, and not using a barrier method of contraception during the study and for 30 days after final study drug administration. In addition, female spouses/partners of male subjects and who are of childbearing potential should also use a highly effective method of birth control during the study and for 30 days after final study drug administration. Highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.
* Subject has significant post-void residual (PVR) volume (\> 150 mL);
* Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the Investigator (for female subjects confirmed by the cough provocation test);
* Subject has a neurological cause for detrusor overactivity;
* Subject has an indwelling catheter or practices intermittent self-catheterization;
* Subject has diabetic neuropathy;
* Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
* Subject has had previous lower urinary tract or pelvic floor surgery (except cystoscopy);
* Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;
* Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis or Crohn's Disease, toxic megacolon, myasthenia gravis or any other condition which makes the use of anticholinergics contraindicated;
* Subject has clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to Screening, such as myocardial infarction, uncontrolled angina, significant ventricular arrhythmias, heart failure and stroke;
* Subject is receiving current non-drug treatment including electro-stimulation therapy (with the exception of a bladder training program or pelvic floor exercises which started more than 30 days prior to Screening);
* Subject is using medications intended to treat OAB or prohibited medications.
* Subject has known or suspected hypersensitivity to solifenacin succinate, mirabegron or any of their excipients;
* Subject has any significant neurological disease or defect affecting bladder function (e.g., neurogenic bladder, systemic or central neurological disease such as multiple sclerosis \[MS\] and Parkinson's disease);
* Subject has severe hypertension which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or an average diastolic blood pressure ≥ 110 mmHg;

* Subject has evidence of a urinary tract infection (UTI) (urine culture containing \> 100,000 cfu/mL). The subject can be enrolled into the study after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture). However, the subject must be re screened if the initial screening visit was \> 28 days;
* Subject has a QT interval \> 450 ms or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia) or is on drug treatment known to be associated with QT prolongation;
* Subject has clinically significant abnormalities on the 12 lead electrocardiogram (ECG);
* Subject has serum creatinine \> 150 µmol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2x upper limit of normal (ULN), gamma-glutamyltransferase (γ-GT) \> 3x ULN, or total bilirubin \> 2x ULN, as assessed in Screening samples;

* Subject had an average total daily urine volume \> 3000 mL as recorded in the micturition diary period;
* Subject has severe hypertension which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or an average diastolic blood pressure ≥ 110 mmHg.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Physician

Role: STUDY_DIRECTOR

Astellas Pharma Europe B.V.

Principal Investigator

Role: PRINCIPAL_INVESTIGATOR

Bristol Urological Institute

Locations

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BY37101

Minsk, , Belarus

Site Status

BY37102

Minsk, , Belarus

Site Status

BY37103

Minsk, , Belarus

Site Status

BY37104

Vitebsk, , Belarus

Site Status

BE32102

Brussels, , Belgium

Site Status

BE32104

Edegem, , Belgium

Site Status

BE32103

Ghent, , Belgium

Site Status

BE32101

Leuven, , Belgium

Site Status

CZ42005

Bohumín, , Czechia

Site Status

CZ42003

Hradec Králové, , Czechia

Site Status

CZ42011

Ostrava, , Czechia

Site Status

CZ42006

Pilsen, , Czechia

Site Status

CZ42001

Prague, , Czechia

Site Status

CZ42007

Prague, , Czechia

Site Status

CZ42009

Prague, , Czechia

Site Status

CZ42010

Roudnice nad Labem, , Czechia

Site Status

CZ42012

Sternberk, , Czechia

Site Status

CZ42002

Uherské Hradiště, , Czechia

Site Status

DK45101

Aarhus N, , Denmark

Site Status

DK45102

Herlev, , Denmark

Site Status

DK45104

Holstebro, , Denmark

Site Status

FI35803

Helsinki, , Finland

Site Status

FI35804

Kouvola, , Finland

Site Status

FI35801

Oulu, , Finland

Site Status

FI35802

Tampere, , Finland

Site Status

FR33104

Colmar, , France

Site Status

FR33108

Dijon, , France

Site Status

FR33103

Orléans, , France

Site Status

FR33111

Paris, , France

Site Status

FR33112

Paris, , France

Site Status

FR33106

Toulouse, , France

Site Status

FR33110

Tours, , France

Site Status

DE49109

Bad Ems, , Germany

Site Status

DE49103

Göttingen, , Germany

Site Status

DE49117

Hagenow, , Germany

Site Status

DE49105

Hettstedt, , Germany

Site Status

DE49108

Leipzig, , Germany

Site Status

DE49110

Neustadt in Sachsen, , Germany

Site Status

DE49118

Reutlingen, , Germany

Site Status

DE49101

Rostock, , Germany

Site Status

DE49111

Sangerhausen, , Germany

Site Status

DE49104

Wismar, , Germany

Site Status

HU36108

Csongrád, , Hungary

Site Status

HU36101

Győr, , Hungary

Site Status

HU36106

Körmend, , Hungary

Site Status

HU36110

Miskolc, , Hungary

Site Status

HU36104

Sopron, , Hungary

Site Status

HU36103

Szekszárd, , Hungary

Site Status

HU36107

Tatabánya, , Hungary

Site Status

IT39103

Avellino, , Italy

Site Status

IT39101

Catanzaro, , Italy

Site Status

IT39105

Florence, , Italy

Site Status

IT39102

Treviglio (BG), , Italy

Site Status

NL31104

Amsterdam, , Netherlands

Site Status

NL31106

Maastricht, , Netherlands

Site Status

NL31102

Sneek, , Netherlands

Site Status

NL31101

Winterswijk, , Netherlands

Site Status

NO47104

Elverum, , Norway

Site Status

NO47102

Hamar, , Norway

Site Status

PL48107

Krakow, , Poland

Site Status

PL48103

Lodz, , Poland

Site Status

PL48108

Lublin, , Poland

Site Status

PL48106

Piaseczno, , Poland

Site Status

PL48104

Puławy, , Poland

Site Status

PL48101

Warsaw, , Poland

Site Status

PL48105

Warsaw, , Poland

Site Status

PL48112

Więcbork, , Poland

Site Status

PL48111

Wroclaw, , Poland

Site Status

PT35102

Coimbra, , Portugal

Site Status

PT35105

Coimbra, , Portugal

Site Status

PT35104

Lisbon, , Portugal

Site Status

PT35107

Lisbon, , Portugal

Site Status

PT35110

Porto, , Portugal

Site Status

PT35101

Porto, , Portugal

Site Status

PT35106

Tomar, , Portugal

Site Status

RO40106

Brasov, , Romania

Site Status

RO40102

Bucharest, , Romania

Site Status

RO40104

Bucharest, , Romania

Site Status

RO40103

Bucharest, , Romania

Site Status

RO40108

Bucharest, , Romania

Site Status

RO40101

Craiova, , Romania

Site Status

RO40105

Craiova, , Romania

Site Status

RO40107

Sibiu, , Romania

Site Status

RU70112

Kazan', , Russia

Site Status

RU70108

Moscow, , Russia

Site Status

RU70110

Moscow, , Russia

Site Status

RU70102

Saint Petersburg, , Russia

Site Status

RU70103

Saint Petersburg, , Russia

Site Status

RU70106

Saint Petersburg, , Russia

Site Status

RU70101

Saint Petersburg, , Russia

Site Status

RU70107

Saint Petersburg, , Russia

Site Status

RU70109

Saint Petersburg, , Russia

Site Status

RU70113

Ufa, , Russia

Site Status

SK42109

Banská Bystrica, , Slovakia

Site Status

SK42112

Bratislava, , Slovakia

Site Status

SK42107

Košice, , Slovakia

Site Status

SK42113

Malacky, , Slovakia

Site Status

SK42104

Nitra, , Slovakia

Site Status

SK42105

Pieštany, , Slovakia

Site Status

SK42106

Piešťany, , Slovakia

Site Status

SK42102

Prešov, , Slovakia

Site Status

SK42108

Trenčín, , Slovakia

Site Status

SK42101

Trenčín, , Slovakia

Site Status

SK42103

Žilina, , Slovakia

Site Status

ES34103

Madrid, , Spain

Site Status

ES34101

Madrid, , Spain

Site Status

ES34109

Madrid, , Spain

Site Status

ES34102

Madrid, , Spain

Site Status

ES34105

Pamplona, , Spain

Site Status

ES34104

Sant Joan d'Alacant, , Spain

Site Status

ES34107

Seville, , Spain

Site Status

SE46101

Gothenburg, , Sweden

Site Status

SE46103

Karlshamn, , Sweden

Site Status

SE46104

Malmo, , Sweden

Site Status

SE46102

Stockholm, , Sweden

Site Status

SE46105

Tanumshede, , Sweden

Site Status

UA38104

Dnipro, , Ukraine

Site Status

UA38102

Donetsk, , Ukraine

Site Status

UA38111

Donetsk, , Ukraine

Site Status

UA38106

Kiev, , Ukraine

Site Status

UA38109

Kiev, , Ukraine

Site Status

UA38107

Lviv, , Ukraine

Site Status

UA38101

Odesa, , Ukraine

Site Status

UA38103

Zaporizhzhya, , Ukraine

Site Status

GB44103

Bristol, , United Kingdom

Site Status

GB44108

Cambridge, , United Kingdom

Site Status

GB44106

Garston, , United Kingdom

Site Status

GB44111

Glasgow, , United Kingdom

Site Status

GB44104

Nantwich, , United Kingdom

Site Status

GB44110

Northwood, , United Kingdom

Site Status

GB44107

Plymouth, , United Kingdom

Site Status

GB44101

Reading, , United Kingdom

Site Status

GB44105

Sandbach, , United Kingdom

Site Status

Countries

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Belarus Belgium Czechia Denmark Finland France Germany Hungary Italy Netherlands Norway Poland Portugal Romania Russia Slovakia Spain Sweden Ukraine United Kingdom

References

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Stoniute A, Madhuvrata P, Still M, Barron-Millar E, Nabi G, Omar MI. Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2023 May 9;5(5):CD003781. doi: 10.1002/14651858.CD003781.pub3.

Reference Type DERIVED
PMID: 37160401 (View on PubMed)

Abrams P, Kelleher C, Staskin D, Rechberger T, Kay R, Martina R, Newgreen D, Paireddy A, van Maanen R, Ridder A. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony). Eur Urol. 2015 Mar;67(3):577-88. doi: 10.1016/j.eururo.2014.02.012. Epub 2014 Feb 19.

Reference Type DERIVED
PMID: 24612659 (View on PubMed)

Related Links

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https://astellasclinicalstudyresults.com/study.aspx?ID=256

Link to results on the Astellas Clinical Study Results website

Other Identifiers

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2010-020601-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

178-CL-100

Identifier Type: -

Identifier Source: org_study_id

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