Back to resultsA Study to Evaluate the Effect of Mirabegron + Solifenacin in Overactive Bladder Patients
Primary Purpose
Overactive Bladder
Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
mirabegron
solifenacin
Sponsored by
About this trial
This is an interventional treatment trial for Overactive Bladder focused on measuring mirabegron, solifenacin
Eligibility Criteria
Inclusion Criteria:
- Female: postmenopausal OAB outpatient
- Male: OAB outpatient who did not wish to have children at all
- Patient had been treated with solifenacin at a stable dose once daily for at least 4 weeks prior to the study
- Patient had a total OAB symptom score (OABSS ) score of ≥3 points and a Question 3 score ≥2 points
Exclusion Criteria:
- Patient had a residual urine volume of ≥100 mL or a maximum flow rate <5 mL/s, or patients with benign prostatic hyperplasia, or lower urinary tract obstruction
- Patient had serious heart disease (myocardial infarction, cardiac failure, uncontrolled angina pectoris, serious arrhythmia, use of pacemaker, etc.), liver disease, kidney disease, immunological disease, lung disease, etc. or patient had malignant tumor (except for malignant tumor that has not been treated for at least 5 y before the start of the screening period with no risk of recurrence)
- Patient had received surgical therapy that may affect the urinary tract function within 24 weeks before the start of the screening period
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Concomitant Group
Arm Description
concomitant administration of mirabegron to solifenacin treated patients
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAEs were defined as AEs observed after the first administration of the study drugs for the treatment period. The investigator assessed the severity of AEs, including abnormal clinical laboratory values, Electrocardiogram (ECG), vital signs, as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A drug-related TEAE was a TEAE with at least a possible relationship to the study drug as assessed by the investigator.
Secondary Outcome Measures
Change From Baseline in OABSS Total Score
The OABSS questionnaire was a questionnaire completed by participants with 4 questions regarding their OAB symptoms. For each participant, the OABSS total score was calculated from the sum total of the score of each question. The total score ranges from 0 to 15 with higher score indicating more symptoms. The OABSS data obtained at week 0 were used as baseline.
Number of Participants Who Achieved Normalization for OABSS Total Score
Normalization for OABSS Total Score was defined as OABSS total score ≤ 2 or OABSS Question 3 score ≤ 1.
Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score
The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Severity Symptom and the Health-related Quality of Life (HRQL). The Severity Symptom section included 6 questions. For each participant, the symptom severity score was derived as a sum of scores for Questions 1 to 6. The total score ranges from 6 to 36 with higher symptom severity score indicating greater symptom bother. OAB-q SF data obtained at week 0 visit were used as baseline.
Change From Baseline in OAB-q SF Total HRQL Score
The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Severity Symptom and the HRQL. The HRQL section included 13 questions. For each participant, the total HRQL score was derived as a sum of scores for Questions 7 to 19. The total score ranges from 13 to 78 with higher total HRQL score indicating greater HRQL. OAB-q SF data obtained at week 0 visit were used as baseline.
Change From Baseline in the Number of Micturitions Per 24 Hours
Participants completed the patient diary (paper document) for 3 days immediately before each visit. The mean number of micturitions per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable "urinated" was indicated, divided by the number of days on which episodes were recorded.
Number for Participants Who Achieved Normalization of the Number of Micturitions Per 24 Hours
Normalization for the mean number of micturitions per 24 hours was defined as < 8 micturitions per 24 hours.
Change From Baseline in the Number of Urgency Episodes Per 24 Hours
Participants completed the patient diary (paper document) for 3 days immediately before each visit. An urgency episode was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable "urgency" was indicated, divided by the number of days on which episodes were recorded. Only participants who had an urgency episode at baseline was included in the analysis.
Number for Participants Who Achieved Normalization of the Number of Urgency Episodes Per 24 Hours
Normalization for the mean number of urgency episodes per 24 hours was defined as no urgency episode per 24 hours.
Change From Baseline in the Number of Incontinence Episodes Per 24 Hours
Participants completed the patient diary (paper document) for 3 days immediately before each visit. An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable "urinary incontinence'" was indicated, divided by the number of days on which episodes were recorded. Only participants who had an incontinence episode at baseline was included in the analysis.
Number for Participants Who Achieved Normalization of the Number of Incontinence Episodes Per 24 Hours
Normalization for the mean number of incontinence episodes per 24 hours was defined as no incontinence episode per 24 hours.
Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours
Participants completed the patient diary (paper document) for 3 days immediately before each visit. An urge incontinence episode was defined as any episode when both urgency and incontinence occurred concurrently. The mean number of incontinence episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable "urgency" and "urinary incontinence'" were indicated, divided by the number of days on which episodes were recorded. Only participants who had an urge incontinence episode at baseline was included in the analysis.
Change From Baseline in the Volume Voided Per Micturition
Participants completed the patient diary (paper document) for 3 days immediately before each visit. The mean volume per micturition was calculated by taking the sum of the urinary volumes where the volume voided was > 0 and where "urinary incontinence" was not indicated in the patient diary, divided by the number of micturitions where the volume voided was > 0 and where "urinary incontinence" was not indicated. Only participants who had volume voided was > 0 at baseline was included in the analysis.
Change From Baseline in the Number of Nocturia Episodes Per Night
Participants completed the patient diary (paper document) for 3 days immediately before each visit. A nocturia episode was defined as waking at night 1 or more times to void. Night time was defined as the period between bedtime and the wake-up time the following day (micturitions at the same time as the wake-up time were excluded). The mean number of nocturia episodes per night was calculated by taking the sum of nocturia episodes in the patient diary where the variable "urinated" was indicated during the night time, divided by the number of nights. Only participants who had a nocturia episode at baseline was included in the analysis.
Change From Baseline in Postvoid Residual (PVR) Volume
Measurement of PVR volume was made using either ultrasonography or urethral catheterization, provided that the same method was used for the same participant throughout the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01745094
Brief Title
A Study to Evaluate the Effect of Mirabegron + Solifenacin in Overactive Bladder Patients
Official Title
Safety and Efficacy of Mirabegron as Add-on Therapy in Patients With Overactive Bladder Treated With Solifenacin: A Postmarketing Open-label Study in Japan
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
October 1, 2012 (Actual)
Primary Completion Date
July 23, 2013 (Actual)
Study Completion Date
July 23, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study was to evaluate the safety and efficacy of mirabegron as add-on therapy in patients with OAB treated with solifenacin.
Detailed Description
The total duration of the study was 18 weeks, comprising a 2-week screening period and a 16-week treatment period. Patients meeting the eligibility criteria for provisional enrollment received the study drug for the screening period (solifenacin) at the same dose as that before the start of the study (2.5 or 5 mg), once daily after breakfast orally for 2 weeks. After the screening period, patients meeting the eligibility criteria for formal enrollment received the study drugs for the treatment period (solifenacin 2.5 or 5 mg and mirabegron 25 mg), once daily after breakfast orally for 16 weeks. Mirabegron dose could be increased to 50 mg at week 8 visit if the patients met all of the following criteria: (1) had an inadequate response to mirabegron at the dose of 25 mg; (2) was judged by the investigator or coinvestigator to have no safety concerns; and (3) agreed to increase the dose.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overactive Bladder
Keywords
mirabegron, solifenacin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
223 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Concomitant Group
Arm Type
Experimental
Arm Description
concomitant administration of mirabegron to solifenacin treated patients
Intervention Type
Drug
Intervention Name(s)
mirabegron
Other Intervention Name(s)
YM178, Betanis
Intervention Description
oral
Intervention Type
Drug
Intervention Name(s)
solifenacin
Other Intervention Name(s)
Vesicare, YM905
Intervention Description
oral
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
TEAEs were defined as AEs observed after the first administration of the study drugs for the treatment period. The investigator assessed the severity of AEs, including abnormal clinical laboratory values, Electrocardiogram (ECG), vital signs, as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A drug-related TEAE was a TEAE with at least a possible relationship to the study drug as assessed by the investigator.
Time Frame
From first dose of study drug up to weeks 16
Secondary Outcome Measure Information:
Title
Change From Baseline in OABSS Total Score
Description
The OABSS questionnaire was a questionnaire completed by participants with 4 questions regarding their OAB symptoms. For each participant, the OABSS total score was calculated from the sum total of the score of each question. The total score ranges from 0 to 15 with higher score indicating more symptoms. The OABSS data obtained at week 0 were used as baseline.
Time Frame
Baseline and week 8, 16
Title
Number of Participants Who Achieved Normalization for OABSS Total Score
Description
Normalization for OABSS Total Score was defined as OABSS total score ≤ 2 or OABSS Question 3 score ≤ 1.
Time Frame
Week 8 and 16
Title
Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Severity Score
Description
The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Severity Symptom and the Health-related Quality of Life (HRQL). The Severity Symptom section included 6 questions. For each participant, the symptom severity score was derived as a sum of scores for Questions 1 to 6. The total score ranges from 6 to 36 with higher symptom severity score indicating greater symptom bother. OAB-q SF data obtained at week 0 visit were used as baseline.
Time Frame
Baseline and week 8, 16
Title
Change From Baseline in OAB-q SF Total HRQL Score
Description
The OAB-q SF questionnaire was a questionnaire completed by participants composed of 2 sections: Severity Symptom and the HRQL. The HRQL section included 13 questions. For each participant, the total HRQL score was derived as a sum of scores for Questions 7 to 19. The total score ranges from 13 to 78 with higher total HRQL score indicating greater HRQL. OAB-q SF data obtained at week 0 visit were used as baseline.
Time Frame
Baseline and week 8, 16
Title
Change From Baseline in the Number of Micturitions Per 24 Hours
Description
Participants completed the patient diary (paper document) for 3 days immediately before each visit. The mean number of micturitions per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable "urinated" was indicated, divided by the number of days on which episodes were recorded.
Time Frame
Baseline and week 4, 8, 12, 16
Title
Number for Participants Who Achieved Normalization of the Number of Micturitions Per 24 Hours
Description
Normalization for the mean number of micturitions per 24 hours was defined as < 8 micturitions per 24 hours.
Time Frame
Week 16
Title
Change From Baseline in the Number of Urgency Episodes Per 24 Hours
Description
Participants completed the patient diary (paper document) for 3 days immediately before each visit. An urgency episode was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable "urgency" was indicated, divided by the number of days on which episodes were recorded. Only participants who had an urgency episode at baseline was included in the analysis.
Time Frame
Baseline and week 4, 8, 12, 16
Title
Number for Participants Who Achieved Normalization of the Number of Urgency Episodes Per 24 Hours
Description
Normalization for the mean number of urgency episodes per 24 hours was defined as no urgency episode per 24 hours.
Time Frame
Week 16
Title
Change From Baseline in the Number of Incontinence Episodes Per 24 Hours
Description
Participants completed the patient diary (paper document) for 3 days immediately before each visit. An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable "urinary incontinence'" was indicated, divided by the number of days on which episodes were recorded. Only participants who had an incontinence episode at baseline was included in the analysis.
Time Frame
Baseline and week 4, 8, 12, 16
Title
Number for Participants Who Achieved Normalization of the Number of Incontinence Episodes Per 24 Hours
Description
Normalization for the mean number of incontinence episodes per 24 hours was defined as no incontinence episode per 24 hours.
Time Frame
Week 16
Title
Change From Baseline in the Number of Urge Incontinence Episodes Per 24 Hours
Description
Participants completed the patient diary (paper document) for 3 days immediately before each visit. An urge incontinence episode was defined as any episode when both urgency and incontinence occurred concurrently. The mean number of incontinence episodes per 24 hours was calculated by taking the sum of all marked episodes in the patient diary where the variable "urgency" and "urinary incontinence'" were indicated, divided by the number of days on which episodes were recorded. Only participants who had an urge incontinence episode at baseline was included in the analysis.
Time Frame
Baseline and week 4, 8, 12, 16
Title
Change From Baseline in the Volume Voided Per Micturition
Description
Participants completed the patient diary (paper document) for 3 days immediately before each visit. The mean volume per micturition was calculated by taking the sum of the urinary volumes where the volume voided was > 0 and where "urinary incontinence" was not indicated in the patient diary, divided by the number of micturitions where the volume voided was > 0 and where "urinary incontinence" was not indicated. Only participants who had volume voided was > 0 at baseline was included in the analysis.
Time Frame
Baseline and week 8, 16
Title
Change From Baseline in the Number of Nocturia Episodes Per Night
Description
Participants completed the patient diary (paper document) for 3 days immediately before each visit. A nocturia episode was defined as waking at night 1 or more times to void. Night time was defined as the period between bedtime and the wake-up time the following day (micturitions at the same time as the wake-up time were excluded). The mean number of nocturia episodes per night was calculated by taking the sum of nocturia episodes in the patient diary where the variable "urinated" was indicated during the night time, divided by the number of nights. Only participants who had a nocturia episode at baseline was included in the analysis.
Time Frame
Baseline and week 4, 8, 12, 16
Title
Change From Baseline in Postvoid Residual (PVR) Volume
Description
Measurement of PVR volume was made using either ultrasonography or urethral catheterization, provided that the same method was used for the same participant throughout the study.
Time Frame
Baseline and week 4, 8, 12, 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female: postmenopausal OAB outpatient
Male: OAB outpatient who did not wish to have children at all
Patient had been treated with solifenacin at a stable dose once daily for at least 4 weeks prior to the study
Patient had a total OAB symptom score (OABSS ) score of ≥3 points and a Question 3 score ≥2 points
Exclusion Criteria:
Patient had a residual urine volume of ≥100 mL or a maximum flow rate <5 mL/s, or patients with benign prostatic hyperplasia, or lower urinary tract obstruction
Patient had serious heart disease (myocardial infarction, cardiac failure, uncontrolled angina pectoris, serious arrhythmia, use of pacemaker, etc.), liver disease, kidney disease, immunological disease, lung disease, etc. or patient had malignant tumor (except for malignant tumor that has not been treated for at least 5 y before the start of the screening period with no risk of recurrence)
Patient had received surgical therapy that may affect the urinary tract function within 24 weeks before the start of the screening period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Pharma Inc
Official's Role
Study Director
Facility Information:
City
Chubu
Country
Japan
City
Hokkaido
Country
Japan
City
Kansai
Country
Japan
City
Kantou
Country
Japan
City
Kyushu
Country
Japan
12. IPD Sharing Statement
Links:
URL
https://www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=169
Description
Link to results on Astellas Clinical Study Results website
Learn more about this trial
A Study to Evaluate the Effect of Mirabegron + Solifenacin in Overactive Bladder Patients
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