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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01340027
First received: April 20, 2011
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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


Condition Intervention Phase
Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Drug: Solifenacin succinate and Mirabegron
Drug: Mirabegron
Drug: Solifenacin succinate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Factorial, Parallel-Group, Active and Placebo-Controlled, Multicenter Dose-Ranging Study to Evaluate the Efficacy, Safety and Tolerability of Six Dose Combinations of Solifenacin Succinate and Mirabegron Compared to Mirabegron and Solifenacin Succinate Monotherapies in the Treatment of Overactive Bladder.

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Change from baseline in mean volume voided per micturition [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in mean number of micturitions/24 hours [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean number of incontinence episodes/24 hours [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean volume voided per micturition at secondary time points [ Time Frame: Baseline, 2 weeks, 4 weeks, 8 weeks and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean number of urgency incontinence episodes/24 hours [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean number of urgency episodes (grade 3 and/or 4)/24 hours (using the Patient Perception of Intensity of Urgency Scale (PPIUS) scale) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean level of urgency [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Patient Perception of Bladder Condition (PPBC) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in symptom bother and health related quality of life scores as assessed by the Overactive Bladder Questionnaire (OAB-q) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in scores as assessed by European Quality of Life questionnaire in 5 Dimensions (EQ-5D) questionnaire [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in scores as assessed by the Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) questionnaire [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in the subject's assessment of Treatment Satisfaction (TS-VAS) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean number of incontinence pads used/24 hours [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean number of nocturia episodes/24 hours [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 2092
Study Start Date: March 2011
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1. Solifenacin low dose and Mirabegron low dose Drug: Solifenacin succinate and Mirabegron
oral
Experimental: 2. Solifenacin low dose and Mirabegron high dose Drug: Solifenacin succinate and Mirabegron
oral
Experimental: 3. Solifenacin medium dose and Mirabegron low dose Drug: Solifenacin succinate and Mirabegron
oral
Experimental: 4. Solifenacin medium dose and Mirabegron high dose Drug: Solifenacin succinate and Mirabegron
oral
Experimental: 5. Solifenacin medium dose Drug: Solifenacin succinate
oral
Other Name: Vesicare
Experimental: 6. Solifenacin high dose and Mirabegron low dose Drug: Solifenacin succinate and Mirabegron
oral
Experimental: 7. Solifenacin high dose and Mirabegron high dose Drug: Solifenacin succinate and Mirabegron
oral
Active Comparator: 8. Solifenacin low dose Drug: Solifenacin succinate
oral
Other Name: Vesicare
Active Comparator: 9. Solifenacin high dose Drug: Solifenacin succinate
oral
Other Name: Vesicare
Active Comparator: 10. Mirabegron low dose Drug: Mirabegron
oral
Other Name: YM178
Active Comparator: 11. Mirabegron high dose Drug: Mirabegron
oral
Other Name: YM178
Placebo Comparator: 12. Placebo Drug: Placebo
oral

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion Criteria at Visit 1/Screening:

    • Subject has a Body Mass Index (BMI) of between 18 and 35 kg/m2 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 OAB (urinary frequency, urgency and/or urgency incontinence) for at least 3 months.
  • Inclusion Criteria at Visit 3/Baseline:

    • 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:

  • Exclusion Criteria at Visit 1/Screening:

    • Subject is breastfeeding, pregnant or intends to become pregnant during the study. The pregnancy test (β-HCG 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 is excluded if using restricted medications under conditions different to those specified in the "Concomitant Medication" section;
    • 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;
  • Exclusion Criteria at Visit 2/Placebo Run-In:

    • 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 (Visit 1b) 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, AST and/or ALT > 2x upper limit of normal (ULN), γ-GT > 3x ULN, or total bilirubin > 2x ULN, as assessed in Screening samples;
  • Exclusion Criteria at Visit 3/Baseline:

    • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01340027

  Hide Study Locations
Locations
Belarus
BY37101
Minsk, Belarus, 220036
BY37102
Minsk, Belarus, 220119
BY37103
Minsk, Belarus, 223010
BY37104
Vitebsk, Belarus, 210037
Belgium
BE32102
Brussels, Belgium, 1090
BE32104
Edegem, Belgium, 2650
BE32103
Gent, Belgium, 9000
BE32101
Leuven, Belgium, 3000
Czech Republic
CZ42005
Bohumín, Czech Republic, 73581
CZ42003
Hradec Kralove, Czech Republic, 500 02
CZ42011
Ostrava, Czech Republic, 700 30
CZ42006
Plzen, Czech Republic, 301 24
CZ42001
Prague, Czech Republic, 128 51
CZ42009
Prague, Czech Republic, 15006
CZ42007
Prague 4, Czech Republic, 14000
CZ42010
Roudnice nad Labem, Czech Republic, 413 01
CZ42012
Sternberk, Czech Republic, 78501
CZ42002
Uherske Hradiste, Czech Republic, 68608
Denmark
DK45101
Aarhus N, Denmark, 8200
DK45102
Herlev, Denmark, 2730
DK45104
Holstebro, Denmark, 7500
Finland
FI35803
Helsinki, Finland, 00029
FI35804
Kouvola, Finland, 45200
FI35801
Oulu, Finland, 90220
FI35802
Tampere, Finland, 33521
France
FR33104
Colmar Cedex, France, 68024
FR33108
Dijon, France, 21079
FR33103
Orleans, France, 45067
FR33111
Paris Cedex 13, France, 75651
FR33112
Paris cedex 20, France, 75970
FR33106
Toulouse, France, 31059
FR33110
Tours, France, 37044
Germany
DE49109
Bad Ems, Germany, 56130
DE49103
Göttingen, Germany, 37075
DE49117
Hagenow, Germany, 19230
DE49105
Hettstedt, Germany, 06333
DE49108
Leipzig, Germany, 04105
DE49110
Neustadt i. Sachsen, Germany, 01844
DE49118
Reutlingen, Germany, 72764
DE49101
Rostock, Germany, 18107
DE49111
Sangerhausen, Germany, 06526
DE49104
Wismar, Germany, 23970
Hungary
HU36108
Csongrád, Hungary, 6640
HU36101
Gyor, Hungary, 9024
HU36106
Körmend, Hungary, 9900
HU36110
Miskolc, Hungary, 3526
HU36104
Sopron, Hungary, 9400
HU36103
Szekszárd, Hungary, 7100
HU36107
Tatabánya, Hungary, 2800
Italy
IT39103
Avellino, Italy, 83100
IT39101
Catanzaro, Italy, 88100
IT39105
Florence, Italy, 50139
IT39102
Treviglio (BG), Italy, 24047
Netherlands
NL31104
Amsterdam, Netherlands, 1100 AD
NL31106
Maastricht, Netherlands
NL31102
Sneek, Netherlands, 8601 ZK
NL31101
Winterswijk, Netherlands, 7101 BN
Norway
NO47104
Elverum, Norway, 2408
NO47102
Hamar, Norway, 2317
Poland
PL48107
Krakow, Poland, 31-530
PL48103
Lodz, Poland, 90-602
PL48108
Lublin, Poland, 20-954
PL48106
Piaseczno, Poland, 05-500
PL48104
Pulawy, Poland, 24-100
PL48105
Warsaw, Poland, 02-929
PL48101
Warsaw, Poland, 02-507
PL48112
Wiecbork, Poland, 89-410
PL48111
Wroclaw, Poland, 01-432
Portugal
PT35105
Coimbra, Portugal, 3041-801
PT35102
Coimbra, Portugal, 3000-075
PT35104
Lisbon, Portugal, 1050-199
PT35107
Lisbon, Portugal, 1649-035
PT35101
Porto, Portugal, 4200-319
PT35110
Porto, Portugal, 4099-001
PT35106
Tomar, Portugal, 2304-909
Romania
RO40106
Brasov, Romania, 500152
RO40108
Bucharest, Romania, 22328
RO40103
Bucharest, Romania, 200642
RO40104
Bucharest, Romania, 050659
RO40102
Bucharest, Romania, 042122
RO40101
Craiova, Romania, 20116
RO40105
Craiova, Romania, 20116
RO40107
Sibiu, Romania, 550245
Russian Federation
RU70112
Kazan, Russian Federation, 420012
RU70110
Moscow, Russian Federation, 115682
RU70108
Moscow, Russian Federation, 105425
RU70101
Saint Petersburg, Russian Federation, 197136
RU70102
Saint Petersburg, Russian Federation, 191015
RU70103
Saint Petersburg, Russian Federation, 194178
RU70107
Saint Petersburg, Russian Federation, 198013
RU70106
St. Petersburg, Russian Federation, 197089
RU70109
St. Petersburg, Russian Federation, 198103
RU70113
Ufa, Russian Federation, 450096
Slovakia
SK42109
Banska Bystrica, Slovakia, 975 01
SK42112
Bratislava, Slovakia, 832 63
SK42107
Kosice, Slovakia, 04011
SK42113
Malacky, Slovakia, 90101
SK42104
Nitra, Slovakia, 949 01
SK42106
Piestany, Slovakia, 921 01
SK42105
Pieštany, Slovakia, 921 01
SK42102
Presov, Slovakia, 08001
SK42108
Trencin, Slovakia, 911 01
SK42101
Trenčín, Slovakia, 91101
SK42103
Zilina, Slovakia
Spain
ES34101
Madrid, Spain, 28041
ES34102
Madrid, Spain, 28905
ES34103
Madrid, Spain, 28031
ES34109
Madrid, Spain, 28046
ES34105
Pamplona, Spain, 31008
ES34104
San Juan de Alicante, Spain, 03550
ES34107
Sevilla, Spain, 41014
Sweden
SE46101
Gothenburg, Sweden, 41263
SE46103
Karlshamn, Sweden, 37435
SE46104
Malmo, Sweden, 21152
SE46102
Stockholm, Sweden, 14186
SE46105
Tanumshede, Sweden, 45781
Ukraine
UA38104
Dnepropetrovsk, Ukraine, 49005
UA38102
Donetsk, Ukraine, 83003
UA38111
Donetsk, Ukraine, 83114
UA38109
Kiev, Ukraine, 04053
UA38106
Kiev, Ukraine, 01023
UA38107
Lviv, Ukraine, 79044
UA38101
Odessa, Ukraine
UA38103
Zaporizhzhya, Ukraine, 69600
United Kingdom
GB44103
Bristol, United Kingdom, BS10 5NB
GB44108
Cambridge, United Kingdom, CB2 2QQ
GB44106
Garston, United Kingdom, WD25 0EA
GB44111
Glasgow, United Kingdom, G20 0XA
GB44104
Nantwich, United Kingdom, CW5 5NX
GB44110
Northwood, United Kingdom, HA6 2RN
GB44107
Plymouth, United Kingdom, PL6 8DH
GB44101
Reading, United Kingdom, RG1 5AN
GB44105
Sandbach, United Kingdom, CW11 1EQ
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Director: Study Physician Astellas Pharma Europe B.V.
Principal Investigator: Principal Investigator Bristol Urological Institute
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT01340027     History of Changes
Other Study ID Numbers: 178-CL-100, 2010-020601-32
Study First Received: April 20, 2011
Last Updated: June 17, 2013
Health Authority: Austria : Federal Ministry for Labour, Health, and Social Affairs
Belarus: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
Denmark: The Ministry of the Interior and Health
Finland: Finnish Medicines Agency
France: Ministry of Health
Germany: Ministry of Health
Hungary: Research Ethics Medical Committee
Italy: Ministry of Health
Netherlands: Ministry of Health, Welfare and Sport
Norway: Ministry of Health and Care Services
Poland: Ministry of Health
Portugal: Ethics Committee for Clinical Research
Romania: Ministry of Public Health
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
Spain: Ministry of Health
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ukraine: Ministry of Health

Keywords provided by Astellas Pharma Inc:
Overactive bladder (OAB)
Frequency
Micturition
Urgency
Urinary incontinence
Urgency incontinence
YM178

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Signs and Symptoms
Urologic Diseases
Urinary Bladder Diseases
Urological Manifestations
Lower Urinary Tract Symptoms
Solifenacin
Mirabegron
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014