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Study to Test the Long Term Safety and Efficacy of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder (TAURUS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00688688
First received: May 29, 2008
Last updated: March 19, 2013
Last verified: March 2013
Results First Received: July 23, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Urinary Bladder, Overactive
Interventions: Drug: Mirabegron
Drug: Tolterodine
Drug: Placebo to Mirabegron
Drug: Placebo to Tolterodine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients who completed the 12-week treatment and safety follow-up periods of studies 178-CL-046 (NCT00689104) or 178-CL-047 (NCT00662909), as well as patients that did not participate in these studies were enrolled into this study if they met all inclusion criteria and none of the exclusion criteria.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After screening, 2792 patients took placebo run-in study drug in a 2-week, single-blind, placebo run-in period. On completion of the run-in period, 2452 eligible patients were randomly assigned to receive mirabegron 50 mg, or mirabegron 100 mg or tolterodine ER 4 mg once daily for 12 months.

Reporting Groups
  Description
Mirabegron 50 mg Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Mirabegron 100 mg Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.
Tolterodine ER 4 mg Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.

Participant Flow:   Overall Study
    Mirabegron 50 mg     Mirabegron 100 mg     Tolterodine ER 4 mg  
STARTED     815     824     813  
Safety Analysis Set (SAF)     812 [1]   820 [1]   812 [1]
Full Analysis Set (FAS)     789 [2]   802 [2]   791 [2]
Full Analysis Set Incontinence (FAS-I)     479 [3]   483 [3]   488 [3]
COMPLETED     629     645     621  
NOT COMPLETED     186     179     192  
Eligibility criterion not met                 7                 7                 10  
Adverse Event                 52                 51                 50  
Lack of Efficacy                 34                 25                 45  
Withdrawal by Subject                 66                 75                 65  
Lost to Follow-up                 14                 7                 7  
Protocol Violation                 6                 9                 11  
Randomized but never received study drug                 1                 0                 0  
Non-compliance with study procedures                 5                 3                 4  
Taking exclusionary medications                 1                 0                 0  
Site closure                 0                 1                 0  
Violation of exclusion criterion                 0                 1                 0  
[1] All randomized patients who took at least 1 dose of double-blind study drug.
[2] All treated patients with a baseline and at least 1 post-baseline micturition measurement.
[3] All FAS patients who had at least 1 incontinence episode at Baseline.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Mirabegron 50 mg Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.
Mirabegron 100 mg Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.
Tolterodine ER 4 mg Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.
Total Total of all reporting groups

Baseline Measures
    Mirabegron 50 mg     Mirabegron 100 mg     Tolterodine ER 4 mg     Total  
Number of Participants  
[units: participants]
  812     820     812     2444  
Age [1]
[units: years]
Mean ± Standard Deviation
  59.2  ± 12.56     60.1  ± 11.92     59.6  ± 12.47     59.6  ± 12.32  
Gender  
[units: participants]
       
Female     602     608     600     1810  
Male     210     212     212     634  
Type of overactive bladder (OAB)  
[units: participants]
       
Urge incontinence     296     305     317     918  
Mixed     232     228     210     670  
Frequency     284     287     285     856  
Duration of OAB symptoms  
[units: months]
Mean ± Standard Deviation
  87.4  ± 96.28     87.9  ± 91.52     83.8  ± 87.34     86.4  ± 91.77  
Summary of previous treatment  
[units: participants]
       
Placebo     190     174     180     544  
Mirabegron 50 mg     170     180     171     521  
Mirabegron 100 mg     183     198     197     578  
Tolterodine ER 4 mg     130     107     108     345  
Naive     139     161     156     456  
Mean number of micturitions per 24 Hours [2]
[units: micturitions]
Mean ± Standard Deviation
  11.12  ± 2.809     11.16  ± 2.917     10.94  ± 2.668     11.08  ± 2.801  
Mean volume voided per micturition [3]
[units: mL]
Mean ± Standard Deviation
  160.4  ± 58.80     164.6  ± 58.62     160.8  ± 56.98     162.0  ± 58.15  
Mean number of urgency episodes (grade 3 or 4) per 24 hours [4]
[units: urgency episodes]
Mean ± Standard Deviation
  5.66  ± 3.601     5.61  ± 3.722     5.44  ± 3.453     5.57  ± 3.594  
Mean level of urgency [5]
[units: scores on a scale]
Mean ± Standard Deviation
  2.45  ± 0.544     2.44  ± 0.525     2.43  ± 0.519     2.44  ± 0.529  
Mean number of nocturia episodes per 24 hours [6]
[units: nocturia episodes]
Mean ± Standard Deviation
  1.83  ± 1.361     1.85  ± 1.404     1.77  ± 1.388     1.82  ± 1.384  
Mean number of pads used per 24 hours [3]
[units: pads]
Mean ± Standard Deviation
  1.06  ± 1.872     0.98  ± 1.769     0.98  ± 1.759     1.01  ± 1.800  
[1] Baseline Measure data are provided for all randomized patients who took at least 1 dose of double-blind study drug (Safety Analysis Set).
[2] The average number of micturitions (urinations) per 24 hours recorded by the patient in a micturition diary for 3 days prior to the Baseline visit.
[3] Recorded by the patient in a micturition diary for 3 days prior to the Baseline visit.
[4] Urgency episodes were those classified by the patient in a 3-day micturition diary as 3 or 4 on the Patient Perception of Intensity of Urgency (PPIUS) scale: 0: No urgency; 1: Mild urgency; 2: Moderate urgency, could delay voiding a short while; 3: Severe urgency, could not delay voiding; 4: Urge incontinence, leaked before arriving to the toilet.
[5] Average of patients’ ratings on the degree of associated urgency for each micturition and/or incontinence episode recorded in a 3-day micturition diary according to the following 5-point categorical scale (Patient Perception of Intensity of Urgency Scale): 0: No urgency; 1: Mild urgency; 2: Moderate urgency, could delay voiding a short while; 3: Severe urgency, could not delay voiding; 4: Urge incontinence, leaked before arriving to the toilet.
[6] The average number of times a patient woke at night to urinate (excluding incontinence only episodes) recorded for 3 days prior to the Baseline visit in the patient micturition diary.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs)   [ Time Frame: From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months. ]

2.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

3.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

4.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

5.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

6.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

7.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

8.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

9.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

10.  Secondary:   Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit   [ Time Frame: Months 1, 3, 6, 9 and 12 ]

11.  Secondary:   Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

12.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

13.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

14.  Secondary:   Change From Baseline to Month 12 and Final Visit in Patient Perception of Bladder Condition (PPBC)   [ Time Frame: Baseline and Month 12 ]

15.  Secondary:   Change From Baseline to Month 12 and Final Visit in Treatment Satisfaction-visual Analog Scale (TS-VAS)   [ Time Frame: Baseline and Month 12 ]

16.  Secondary:   Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed   [ Time Frame: Baseline and Months 3, 6 and 12 ]

17.  Secondary:   Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working   [ Time Frame: Baseline and Months 3, 6 and 12 ]

18.  Secondary:   Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment   [ Time Frame: Baseline and Months 3, 6 and 12 ]

19.  Secondary:   Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment   [ Time Frame: Baseline and Months 3, 6 and 12 ]

20.  Secondary:   Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score   [ Time Frame: Baseline and Month 12 ]

21.  Secondary:   Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score   [ Time Frame: Baseline and Month 12 ]

22.  Secondary:   Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score   [ Time Frame: Baseline and Month 12 ]

23.  Secondary:   Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score   [ Time Frame: Baseline and Month 12 ]

24.  Secondary:   Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score   [ Time Frame: Baseline and Month 12 ]

25.  Secondary:   Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)   [ Time Frame: Baseline and Months 1, 3, 6, 9 and 12 ]

26.  Secondary:   Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician   [ Time Frame: Baseline and Months 3, 6 and 12 ]

27.  Secondary:   Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC)   [ Time Frame: Baseline and Month 12 ]

28.  Secondary:   Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram   [ Time Frame: From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Director, Global Medical Sciences
Organization: Astellas Pharma Global Development, Inc.
e-mail: ClinicalTrials.Disclosure@us.astellas.com


Publications:

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00688688     History of Changes
Other Study ID Numbers: 178-CL-049, 2007-001452-39
Study First Received: May 29, 2008
Results First Received: July 23, 2012
Last Updated: March 19, 2013
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belarus: Ministry of Health
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Iceland: Icelandic Medicines Control Agency
Ireland: Irish Medicines Board
Italy: Ethics Committee
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Ukraine: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
Morocco: Ministry of Public Health