Postmarketing Study to Evaluate add-on Therapy With Anticholinergics in Patients With Overactive Bladder (OAB) on Mirabegron.

NCT02294396 | Completed Phase 4 Results

• 1 other identifier: 178-CL-112
• Study Type: interventional
• Target: 649
• Locations: 1 country
• Sites: 7

Brief Summary

The objective of the study was to evaluate the safety and efficacy of add-on therapy with anticholinergics in patients with OAB on mirabegron.

Conditions

Overactive Bladder (OAB)

Keywords

Anticholinergic; Overactive Bladder (OAB); Mirabegron; YM178

Outcome Measures

Primary Outcomes (1)

• 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 week 52

Secondary Outcomes (15)

• Change From Baseline in Overactive Bladder Symptom Score (OABSS) Total Score

  Baseline and week 4, 8, 12, 16, 28 and 52

• Number of Participants Who Achieved Normalization for OABSS Total Score

  Week 52 (end of treatment)

• Change From Baseline in Overactive Bladder Questionnaire Short Form (OAB-q SF) Symptom Severity Score

  Baseline and week 12, 28 and 52

• Change From Baseline in OAB-q SF Total HRQL Score

  Baseline and week 12, 28 and 52

• Change From Baseline in the Mean Number of Micturitions Per 24 Hours

  Baseline and week 4, 8, 12, 16, 28, 40, 52

Study Arms (4)

Mirabegron + Solifenacin

EXPERIMENTAL

Participants received mirabegron 50 mg and solifenacin 5 mg once daily after breakfast orally for 8 weeks. In the next 44 weeks, participants continued to receive mirabegron 50 mg, but received an increased dose of solifenacin 10 mg, if the treatment was not effective.

Drug: Mirabegron tablet; Drug: Solifenacin tablet

Mirabegron + Propiverine

EXPERIMENTAL

Participants received mirabegron 50 mg and propiverine 20 mg once daily after breakfast orally for 8 weeks. In the next 44 weeks, participants continued to receive mirabegron 50 mg, but received an increased dose of propiverine 40 mg, if the treatment was not effective.

Drug: Mirabegron tablet; Drug: Propiverine tablet

Mirabegron + Imidafenacin

EXPERIMENTAL

Participants received mirabegron 50 mg and imidafenacin 0.2 mg once daily after breakfast orally for 8 weeks. In the next 44 weeks, participants continued to receive mirabegron 50 mg, but received an increased dose of imidafenacin 0.4 mg, if the treatment was not effective.

Drug: Mirabegron tablet; Drug: Imidafenacin tablet

Mirabegron + Tolterodine

EXPERIMENTAL

Participants received mirabegron 50 mg and tolterodine 4 mg once daily after breakfast orally for 52 weeks.

Drug: Mirabegron tablet; Drug: Tolterodine capsule

Interventions

Mirabegron tablet DRUG

orally administered at a dose of 1 tablet once daily after breakfast

Also known as: YM178

Mirabegron + Imidafenacin; Mirabegron + Propiverine; Mirabegron + Solifenacin; Mirabegron + Tolterodine

Solifenacin tablet DRUG

orally administered at a dose of 1 tablet once daily after breakfast (could be increased to 2 tablets)

Mirabegron + Solifenacin

Propiverine tablet DRUG

orally administered at a dose of 1 tablet once daily after breakfast (could be increased to 1 tablet twice daily after breakfast and after dinner)

Mirabegron + Propiverine

Imidafenacin tablet DRUG

orally administered at a dose of 1 tablet (0.1 mg tablet) twice daily after breakfast and after dinner (could be increased to 2 tablets twice daily after breakfast and after dinner)

Mirabegron + Imidafenacin

Tolterodine capsule DRUG

orally administered at a dose of 1 capsule once daily after breakfast (could not be increased)

Mirabegron + Tolterodine

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female: OAB outpatient who had been postmenopausal for at least 1 year
• Male: OAB outpatient who had no wish to have children in the future
• Patient had been under treatment with mirabegron at a stable dose of 50 mg once daily for at least 6 weeks before the start of the screening period
• Patient capable of walking to the bathroom without assistance
• Patient had a total Overactive Bladder Symptom Score (OABSS) of ≥3 points and a Question 3 score of ≥2 points

You may not qualify if:

• Patient had an established diagnosis of stress urinary incontinence (patient had no symptom other than stress urinary incontinence)
• Patient had urinary tract infection (cystitis, prostatitis, etc.), urinary calculus (ureteric calculus, urethral calculus, bladder calculus, etc.), interstitial cystitis, or a history of recurrent urinary tract infection (at least 3 episodes within 24 weeks before the start of the screening period)
• Patient had a residual urine volume of ≥100 mL at week -2 visit or patient with benign prostatic hyperplasia or lower urinary tract obstruction
• Patient had uncontrolled hypertension (sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg at week -2 visit)
• Patient had a pulse rate of ≥110 bpm or \<50 bpm at week -2 visit
• Patient had a contraindication to antimuscarinics (urinary retention; obstruction in thepylorus, duodenum, or intestine; paralytic ileus; gastric/intestinal atony; myasthenia gravis; and decreased gastrointestinal motility/tone, etc.)
• Patient had glaucoma, ulcerative colitis, hyperthyroidism, dementia, cognitive dysfunction, parkinsonism symptoms, or clinically significant cerebrovascular disorder
• 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 a history of malignant tumor (except for malignant tumor that had not been treated for at least 5 years before the start of the screening period with no risk of recurrence)
• Patient had drug hypersensitivity to β-agonists or anticholinergics
• Patient was under treatment with flecainide acetate or propafenone hydrochloride
• Patient had long QT syndrome, patient was vulnerable to arrhythmia such as bradycardia or acute myocardial ischemia, patient had hypokalemia, and patient had ischemic heart disease such as angina pectoris
• Patient had used any prohibited concomitant medication within 4 weeks before the start of the screening period
• Patient was under catheterization or intermittent self-catheterization or patient had pelvic organ prolapse that affected the urinary tract function
• Patient had received radiotherapy that affected the urinary tract function
• Patient had received surgical therapy that may have affected the urinary tract function within 24 weeks before the start of the screening period

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (7)

Unknown Facility

Chugoku, Japan

Location

Unknown Facility

Chūbu, Japan

Location

Unknown Facility

Hokkaido, Japan

Location

Unknown Facility

Kansai, Japan

Location

Unknown Facility

Kantou, Japan

Location

Unknown Facility

Kyushu, Japan

Location

Unknown Facility

Tōhoku, Japan

Location

Related Links

• Link to results on Astellas Clinical Study Results website

MeSH Terms

Conditions

Urinary Bladder, Overactive

Interventions

mirabegron; Solifenacin Succinate; propiverine; imidafenacin; Tolterodine Tartrate

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylpropanolamine; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cresols; Phenols

Results Point of Contact

• Title: Medical Director
• Organization: Astellas Pharma Inc.

astellas.resultsdisclosure@astellas.com

+81-3-3244-0512

Study Officials

• Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: November 19, 2014
• Study Start: October 28, 2014
• Primary Completion: September 7, 2016
• Study Completion: September 7, 2016
• Last Updated: October 31, 2024
• Results First Posted: December 24, 2018

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

JP (7)