A Study to Evaluate the Effect of Mirabegron + Solifenacin in Overactive Bladder Patients

Safety and Efficacy of Mirabegron as Add-on Therapy in Patients With Overactive Bladder Treated With Solifenacin: A Postmarketing Open-label Study in Japan

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.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: solifenacin; Drug: mirabegron

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.

• Study Type: Interventional
• Enrollment (Actual): 223
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Chubu, Japan
  • Hokkaido, Japan
  • Kansai, Japan
  • Kantou, Japan
  • Kyushu, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concomitant Group; concomitant administration of mirabegron to solifenacin treated patients	Drug: solifenacin; oral; Other Names: Vesicare; YM905; Drug: mirabegron; oral; Other Names: YM178; Betanis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose of study drug up to weeks 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and week 8, 16
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.	Week 8 and 16
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.	Baseline and week 8, 16
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.	Baseline and week 8, 16
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.	Baseline and week 4, 8, 12, 16
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.	Week 16
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.	Baseline and week 4, 8, 12, 16
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.	Week 16
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.	Baseline and week 4, 8, 12, 16
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.	Week 16
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.	Baseline and week 4, 8, 12, 16
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.	Baseline and week 8, 16
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.	Baseline and week 4, 8, 12, 16
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.	Baseline and week 4, 8, 12, 16

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2012
• Primary Completion (Actual): July 23, 2013
• Study Completion (Actual): July 23, 2013

Study Registration Dates

• First Submitted: December 6, 2012
• First Submitted That Met QC Criteria: December 6, 2012
• First Posted (Estimate): December 7, 2012

Study Record Updates

• Last Update Posted (Actual): February 28, 2018
• Last Update Submitted That Met QC Criteria: January 31, 2018
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: solifenacin; mirabegron
• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron; Solifenacin Succinate
• Other Study ID Numbers: 178-CL-110

Drug and device information, study documents

• 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