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

History of Changes

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
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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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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

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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 ]

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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 ]

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3. Secondary:

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

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4. Secondary:

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

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5. Secondary:

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

Show Outcome Measure 5

6. Secondary:

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

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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 ]

Show Outcome Measure 7

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 ]

Show Outcome Measure 8

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 ]

Show Outcome Measure 9

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 ]

Show Outcome Measure 10

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 ]

Show Outcome Measure 11

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 ]

Show Outcome Measure 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 ]

Show Outcome Measure 13

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 ]

Show Outcome Measure 14

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 ]

Show Outcome Measure 15

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 ]

Show Outcome Measure 16

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 ]

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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 ]

Show Outcome Measure 18

19. Secondary:

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

Show Outcome Measure 19

20. Secondary:

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

Show Outcome Measure 20

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 ]

Show Outcome Measure 21

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 ]

Show Outcome Measure 22

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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

Show Outcome Measure 28

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 ]

Show Outcome Measure 29

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 ]

Show Outcome Measure 30

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 ]

Show Outcome Measure 31

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 ]

Show Outcome Measure 32

33. Secondary:

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

Show Outcome Measure 33

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 ]

Show Outcome Measure 34

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 ]

Show Outcome Measure 35

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 ]

Show Outcome Measure 36

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 ]

Show Outcome Measure 37

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 ]

Show Outcome Measure 38

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 ]

Show Outcome Measure 39

Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site’s manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication for an additional 60 days to seek patent protection.

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

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

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