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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00912964
First received: June 1, 2009
Last updated: September 17, 2012
Last verified: September 2012
Results First Received: July 17, 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: Placebo

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After screening, 2030 patients took placebo run-in study drug in a 2-week, single-blind, placebo run-in period. On completion of the run-in period, 1306 eligible patients were randomly assigned to receive placebo, mirabegron 25 mg or mirabegron 50 mg for 12 weeks.

Reporting Groups
  Description
Placebo Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.
Mirabegron 25 mg Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.
Mirabegron 50 mg Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.

Participant Flow:   Overall Study
    Placebo     Mirabegron 25 mg     Mirabegron 50 mg  
STARTED     433     433     440  
Safety Analysis Set (SAF)     433 [1]   432 [1]   440 [1]
Full Analysis Set (FAS)     415 [2]   410 [2]   426 [2]
Full Analysis Set Incontinence (FAS-I)     262 [3]   254 [3]   257 [3]
COMPLETED     367     387     386  
NOT COMPLETED     66     46     54  
Eligibility criterion not met                 1                 1                 0  
Adverse Event                 15                 18                 12  
Lack of Efficacy                 11                 4                 3  
Withdrawal by Subject                 20                 12                 18  
Lost to Follow-up                 4                 3                 3  
Protocol Violation                 5                 3                 8  
Taking exclusionary medications                 7                 4                 8  
Medical History                 1                 0                 0  
Non-compliance with study procedures                 2                 0                 0  
Violation of exclusion criterion                 0                 0                 2  
Randomized but never received study drug                 0                 1                 0  
[1] All randomized patients who took at least 1 dose of double-blind study drug.
[2] Treated patients with a baseline and at least 1 post-baseline micturition measurement.
[3] Full analysis set 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
Placebo Participants received matching mirabegron placebo tablets orally once a day for 12 weeks.
Mirabegron 25 mg Participants received mirabegron 25 mg tablets orally once a day for 12 weeks.
Mirabegron 50 mg Participants received mirabegron 50 mg tablets orally once a day for 12 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo     Mirabegron 25 mg     Mirabegron 50 mg     Total  
Number of Participants  
[units: participants]
  433     432     440     1305  
Age [1]
[units: years]
Mean ± Standard Deviation
  58.2  ± 13.73     58.5  ± 12.85     60.3  ± 12.22     59.0  ± 12.97  
Gender  
[units: participants]
       
Female     301     293     303     897  
Male     132     139     137     408  
Race/Ethnicity, Customized  
[units: participants]
       
White     389     394     400     1183  
Black or African American     35     32     33     100  
Asian     7     5     5     17  
Other     2     1     2     5  
Type of overactive bladder (OAB)  
[units: participants]
       
Urge Incontinence     126     168     169     463  
Mixed     145     129     154     428  
Frequency     162     135     117     414  
Duration of OAB symptoms  
[units: months]
Mean ± Standard Deviation
  91.3  ± 96.82     96.3  ± 113.77     92.7  ± 97.88     93.4  ± 103.02  
Mean number of micturitions per 24 hours [2]
[units: micturitions]
Mean ± Standard Deviation
  11.54  ± 2.979     11.66  ± 3.117     11.69  ± 3.227     11.63  ± 3.108  
Mean volume voided per micturition [3]
[units: mL]
Mean ± Standard Deviation
  163.5  ± 56.39     165.4  ± 57.24     158.4  ± 52.17     162.4  ± 55.33  
Mean number of urgency episodes (grade 3 or 4) per 24 hours [4]
[units: urgency episodes]
Mean ± Standard Deviation
  5.43  ± 3.335     5.54  ± 3.622     5.81  ± 3.559     5.60  ± 3.508  
Mean level of urgency [5]
[units: scores on a scale]
Mean ± Standard Deviation
  2.36  ± 0.550     2.37  ± 0.573     2.41  ± 0.556     2.38  ± 0.560  
Mean number of nocturia episodes per 24 hours [6]
[units: nocturia episodes]
Mean ± Standard Deviation
  1.82  ± 1.332     1.94  ± 1.552     2.03  ± 1.528     1.93  ± 1.465  
Mean number of pads used per 24 hours [3]
[units: pads]
Mean ± Standard Deviation
  0.91  ± 1.786     0.79  ± 1.449     0.84  ± 1.700     0.85  ± 1.666  
[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) 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:   Change From Baseline to End of Treatment (Final Visit) in Mean Number of Incontinence Episodes Per 24 Hours   [ Time Frame: Baseline and Week 12 ]

2.  Primary:   Change From Baseline to End of Treatment (Final Visit) in Mean Number of Micturitions Per 24 Hours   [ Time Frame: Baseline and Week 12 ]

3.  Secondary:   Change From Baseline to End of Treatment (Final Visit) in Mean Volume Voided Per Micturition   [ Time Frame: Baseline and Week 12 ]

4.  Secondary:   Change From Baseline to Week 4 in Mean Number of Incontinence Episodes Per 24 Hours   [ Time Frame: Baseline and Week 4 ]

5.  Secondary:   Change From Baseline to Week 4 in Mean Number of Micturitions Per 24 Hours   [ Time Frame: Baseline and Week 4 ]

6.  Secondary:   Change From Baseline to End of Treatment (Final Visit) in Mean Level of Urgency   [ Time Frame: Baseline and Week 12 ]

7.  Secondary:   Change From Baseline to End of Treatment (Final Visit) in Mean Number of Urgency Incontinence Episodes Per 24 Hours   [ Time Frame: Baseline and Week 12 ]

8.  Secondary:   Change From Baseline to End of Treatment (Final Visit) in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours   [ Time Frame: Baseline and Week 12 ]

9.  Secondary:   Change From Baseline to Week 8 and Week 12 in Mean Number of Micturitions Per 24 Hours   [ Time Frame: Baseline and Weeks 8 and 12 ]

10.  Secondary:   Change From Baseline to Week 8 and Week 12 in Mean Number of Incontinence Episodes Per 24 Hours   [ Time Frame: Baseline and Weeks 8 and 12 ]

11.  Secondary:   Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

12.  Secondary:   Change From Baseline to Week 4, Week 8 and Week 12 in Mean Number of Urgency Incontinence Episodes Per 24 Hours   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

13.  Secondary:   Change From Baseline to Week 4, Week 8 and Week 12 in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

14.  Secondary:   Change From Baseline to Week 4, Week 8 and Week 12 in Mean Level of Urgency   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

15.  Secondary:   Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

16.  Secondary:   Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

17.  Secondary:   Percentage of Participants With Zero Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit   [ Time Frame: Weeks 4, 8 and 12 ]

18.  Secondary:   Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

19.  Secondary:   Percentage of Responders for Mean Level of Urgency   [ Time Frame: Baseline and Week 12 ]

20.  Secondary:   Percentage of Responders for Number of Grade 3 or 4 Urgency Episodes   [ Time Frame: Baseline and Week 12 ]

21.  Secondary:   Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

22.  Secondary:   Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

23.  Secondary:   Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed   [ Time Frame: Baseline and Week 12 ]

24.  Secondary:   Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working   [ Time Frame: Baseline and Week 12 ]

25.  Secondary:   Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment   [ Time Frame: Baseline and Week 12 ]

26.  Secondary:   Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment   [ Time Frame: Baseline and Week 12 ]

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

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

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

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

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

32.  Secondary:   Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

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

34.  Secondary:   Change From Baseline to Week 12 and Final Visit in Treatment Satisfaction on Visual Analog Scale (TS-VAS)   [ Time Frame: Baseline and Week 12 ]

35.  Secondary:   Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

36.  Secondary:   Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Clinician Global Impression Scale   [ Time Frame: Baseline and Week 12 ]

37.  Secondary:   Summary of Baseline, Week 12 and Final Visit Change in Bladder Symptoms on the Patient Global Impression Scale   [ Time Frame: Baseline and Week 12 ]

38.  Secondary:   Summary of Baseline, Week 12 and Final Visit Change in Overall Condition on the Patient Global Impression Scale   [ Time Frame: Baseline and Week 12 ]

39.  Secondary:   Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit   [ Time Frame: Baseline and Week 12 ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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.  


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


No publications provided by Astellas Pharma Inc

Publications automatically indexed to this study:

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00912964     History of Changes
Other Study ID Numbers: 178-CL-074, 2008-007087-42
Study First Received: June 1, 2009
Results First Received: July 17, 2012
Last Updated: September 17, 2012
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Canada: Health Canada