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

  Show 133 Study Locations
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 29, 2014