A Double-Blind, Randomized, Parallel Group, Multi-Centre Study to Evaluate the Efficacy and Safety of Mirabegron Compared to Solifenacin in Subjects With Overactive Bladder (OAB) Treated With Antimuscarinics and Dissatisfied Due to Lack of Efficacy

Astellas Pharma Europe Ltd.217 sites in 8 countries1,887 target enrollmentJune 12, 2012

ConditionsUrologic Diseases Urinary Bladder, Overactive Urinary Bladder Diseases

InterventionsSolifenacin succinate Mirabegron

DrugsMirabegron Solifenacin succinate

Overview

Phase: Phase 3
Intervention: Solifenacin succinate
Conditions: Urologic Diseases
Sponsor: Astellas Pharma Europe Ltd.
Enrollment: 1887
Locations: 217
Primary Endpoint: Change From Baseline to Final Visit in the Mean Number of Micturitions Per 24 Hours
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of the study was to assess the efficacy, safety and tolerability of mirabegron 50 mg versus (vs) solifenacin 5 mg in the treatment of patients with OAB who were dissatisfied with their treatment due to lack of efficacy.

Registry

clinicaltrials.gov

Start Date

June 12, 2012

End Date

April 24, 2013

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Astellas Pharma Europe Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject is willing and able to complete the micturition diary and questionnaires correctly
•Subject has symptoms of OAB (urinary frequency and urgency with or without urgency incontinence) for at least 3 months
•Subject is currently or has previously received at least one antimuscarinic agent intended to treat their OAB. The last antimuscarinic must have been taken for at least 4 weeks and taken within 6 months prior to the Screening Visit

Exclusion Criteria

•Female subject is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential is sexually active and not practicing a highly reliable method of birth control
•Subject has neurogenic bladder
•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 a cough provocation test)
•Subject has an indwelling catheter or practices intermittent self-catheterization
•Subject has diabetic neuropathy
•Subject has evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs
•Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis, toxic megacolon, myasthenia gravis or any other medical condition which makes the use of anticholinergics contraindicated
•The subject is currently receiving or has a history of treatment with intravesical botulinum toxin (cosmetic use is acceptable) or resiniferatoxin within 9 months prior to screening
•Subject receives 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 has moderate to severe hepatic impairment

Arms & Interventions

Solifenacin 5 mg

Participants who received solifenacin 5 mg once daily for 12 weeks.

Intervention: Solifenacin succinate

Mirabegron 50 mg

Participants who received mirabegron 50 mg once daily for 12 weeks.

Intervention: Mirabegron

Outcomes

Primary Outcomes

Change From Baseline to Final Visit in the Mean Number of Micturitions Per 24 Hours

Time Frame: Baseline and final visit (up to Week 12)

A micturition is any voluntary urination (excluding incontinence only episodes). The mean number of micturitions per 24 hours were calculated from the data recorded by the participant during the 3-day micturition diary period.

Secondary Outcomes

Percentage of Participants With Major Improvement in PPBC: ≥2 Point Improvement at Week 12 and Final Visit(Baseline to Week 12)
Percentage of Participants With 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and Final Visit(Week 4, Week 8, Week 12)
Percentage of Participants With Zero Incontinence Episodes at Weeks 4, 8, 12 and Final Visit(Week 4, Week 8, Week 12)
Change From Baseline to Week 4 in Mobility Scores as Assessed by the European Quality of Life 5-Dimensions (EQ-5D-5L) Questionnaire(Baseline and Week 4)
Percentage of Participants Reporting at Least One Treatment-emergent Adverse Event of Dry Mouth, Constipation or Blurred Vision During Double-blind Treatment Period(From first dose of study drug up to 30 days after last dose of study drug (up to 16 weeks))
Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Micturitions Per 24 Hours(Baseline and Week 4, Week 8, Week 12)
Number of Incontinence Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit(Week 4, Week 8, Week 12)
Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Incontinence Episodes Per 24 Hours(Baseline and Week 4, Week 8, Week 12)
Number of Urgency Incontinence Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit(Week 4, Week 8, Week 12)
Change From Baseline to 4, 8 and 12 Weeks of Treatment in Mean Number of Urgency Incontinence Episodes Per 24 Hours(Baseline and Week 4, Week 8, Week 12)
Change From Baseline to 4, 8 and 12 Weeks of Treatment and at the Final Visit in Mean Number of Urgency Episodes (Grade 3 or 4) Per 24 Hours(Baseline and Week 4, Week 8, Week 12)
Change From Baseline to 4, 8 and 12 Weeks of Treatment and at the Final Visit in Mean Level of Urgency(Baseline and Week 4, Week 8, Week 12)
Number of Pads Used at 4, 8 and 12 Weeks of Treatment and at the Final Visit(Week 4, Week 8, Week 12)
Change From Baseline in Mean Number of Pads Used Per 24 Hours After 4, 8 and 12 Weeks of Treatment(Baseline and Week 4, Week 8 , Week 12)
Number of Nocturia Episodes at 4, 8 and 12 Weeks of Treatment and at the Final Visit(Week 4, Week 8, Week 12)
Change From Baseline in Mean Number of Nocturia Episodes Per 24 Hours After 4, 8 and 12 Weeks of Treatment(Baseline and Week 4, Week 8, Week 12)
Percentage of Participants With Normalization of Micturitions at Weeks 4, 8, 12 and Final Visit(Week 4, Week 8, Week 12)
Change From Baseline to Week 4 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 4)
Change From Baseline to Week 4 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 4)
Change From Baseline to Week 4 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 4)
Change From Baseline to Week 4 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 4)
Change From Baseline to Week 8 in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 8)
Change From Baseline to Week 8 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 8)
Change From Baseline to Week 8 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 8)
Change From Baseline to Week 8 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 8)
Change From Baseline to Week 8 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 8)
Change From Baseline to Week 12 in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 12)
Change From Baseline to Week 12 in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 12)
Change From Baseline to Week 12 in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 12)
Change From Baseline to Week 12 in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 12)
Change From Baseline to Week 12 in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and Week 12)
Change From Baseline to Final Visit in Mobility Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and final visit (up to Week 12))
Change From Baseline to Final Visit in Self-care Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and final visit (up to Week 12))
Change From Baseline to Final Visit in Usual Activities Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and final visit (up to Week 12))
Percentage of Participants With Improvement in Symptom Bother Score as Assessed by the OAB-q: ≥ 10 Points Improvement in OAB-q at Week 12 and Final Visit(Baseline to Week 12)
Change From Baseline to Final Visit in Pain/Discomfort Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and final visit (up to Week 12))
Change From Baseline to Final Visit in Anxiety/Depression Scores as Assessed by the EQ-5D-5L Questionnaire(Baseline and final visit (up to Week 12))
Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Symptom Bother Score as Assessed by the Overactive Bladder Questionnaire (OAB-q)(Baseline and Week 4, Week 8, Week 12)
Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Total Health-Related Quality of Life (HRQoL) Score as Assessed by the OAB-q(Baseline and Week 4, Week 8, Week 12)
Change From Baseline to Weeks 4, 8, 12, and at the Final Visit in Patient Perception of Bladder Condition (PPBC)(Baseline and Week 4, Week 8, Week 12)
Change From Baseline to Week 12 and the Final Visit in the Patient's Assessment of Treatment Satisfaction (TS)-Visual Analog Scale (VAS)(Baseline and Week 12)
Percentage of Participants With Improvement in HRQoL Scales as Assessed by the OAB-q: ≥10 Points Improvement in OAB-q at Week 12 and Final Visit(Baseline to Week 12)
Percentage of Participants With Improvement in PPBC: ≥1 Point Improvement at Week 12 and Final Visit(Baseline to Week 12)
Change From Baseline to Week 12 and the Final Visit in the Patient's Assessment of Treatment Satisfaction Questionnaire-Likert Scale(Baseline and Week 12)
Percentage of Participants With Improvement of Treatment Satisfaction Questionnaire - Likert Scale: ≥1, ≥2, ≥3, ≥4, ≥5, and 6-point Improvement From Baseline to Week 12(Baseline to Week 12)
Percentage of Participants With Improvement in Treatment Satisfaction Questionnaire - Likert Scale: ≥1, ≥2, ≥3, ≥4, ≥5, and 6-point Improvement From Baseline to Final Visit(Baseline to final visit (up to Week 12))