Study to Test the Efficacy and Safety of YM178 in Subjects With Symptoms of Overactive Bladder (Blossom)

A Randomized, Double-blind, Parallel Group, Proof of Concept Study of YM178 in Comparison With Placebo and Tolterodine in Patients With Symptomatic Overactive Bladder

The study is intended to test efficacy, safety and tolerability of two doses of YM178 against placebo and tolterodine to treat patients with symptoms of over active bladder.

Study Overview

• Status: Completed
• Conditions: Urinary Bladder, Overactive
• Intervention / Treatment: Drug: Placebo; Drug: YM178; Drug: tolterodine

Detailed Description

This is a multinational, multicenter, double-blind, double-dummy,

randomized, parallel group, placebo and active controlled phase II proof-of concept study. Patients are enrolled into a single-blind, 2-week placebo run in

period after which they are randomized to 4 weeks of double-blind

treatment with YM178 (low dose and high dose), placebo or tolterodine. Subsequently patients will be followed for an additional 2 weeks

with single-blind placebo treatment. There are 6 visits in total: visit 1 at

enrolment, visit 2 (baseline) after the 2-week placebo run-in, visits 3, 4 and 5

after 1, 2 and 4 weeks of double-blind treatment respectively, and visit 6

after a 2-week follow-up.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Site: 12
  • Edegem, Belgium, 2650
    • Site: 13
  • Gent, Belgium, 9000
    • Site: 11
  • Leuven, Belgium, 3000
    • Site: 10
• Czechia
  • Melnik, Czechia, 276 01
    • Site: 25
  • Prague, Czechia, 128 08
    • Site: 22
  • Prague, Czechia, 140 59
    • Site: 24
  • Prague, Czechia, 180 81
    • Site: 20
  • Usti nad Labem, Czechia, 40001
    • Site: 21
  • Usti nad Labem, Czechia, 401 13
    • Site: 23
• Germany
  • Bad Ems, Germany, 56130
    • Site: 32
  • Emmendingen, Germany, 79312
    • Site: 30
  • Frankfurt, Germany, 60326
    • Site: 35
  • Hagenow, Germany, 19230
    • Site: 34
  • Hamburg, Germany, 20253
    • Site: 33
  • Koblenz, Germany, 56068
    • Site: 36
  • Trier, Germany, 54290
    • Site: 31
• Spain
  • Alzira-Valencia, Spain, 46600
    • Site: 42
  • Madrid, Spain, 28046
    • Site: 40
  • Miranda de Ebro, Spain, 09200
    • Site: 43
• Sweden
  • Gotenburg, Sweden, 413 45
    • Site: 55
  • Linkoping, Sweden, 582 24
    • Site: 53
  • Lund, Sweden, 221 85
    • Site: 50
  • Stockholm, Sweden, 141 86
    • Site: 51
  • Uppsala, Sweden, 751 85
    • Site: 52
• United Kingdom
  • Bimingham, United Kingdom, B15 2TG
    • Site: 64
  • London, United Kingdom, N19 5LW
    • Site: 62
  • London, United Kingdom, W1P 7PN
    • Site: 63
  • Sheffield, United Kingdom, S10 2JF
    • Site: 60
  • Swansea, United Kingdom, SA6 6NL
    • Site: 61

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is willing and able to complete the micturition diary correctly.
• Symptoms of overactive bladder (urinary frequency and urgency with or without incontinence) for ≥ 3 months

At randomization:

• Patient must experience frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period
• Patient must experience at least 3 episodes of urgency (grade 3 or 4) with or without incontinence, during the 3-day micturition diary period

Exclusion Criteria:

• Pregnant women or women who intend to become pregnant during the study or women of childbearing potential who are sexually active and practicing an unreliable method of birth control or will be lactating during the study. Reliable contraceptive methods are intra-uterine devices, contraceptive pills of combination type, hormonal implants, contraceptive patches and injectable contraceptives
• Clinically significant outflow obstruction (at the discretion of the investigator)
• Significant post void residual volume (PVR>200ml)
• Significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor as determined by the investigator (for female patients confirmed by a cough provocation test)
• Patients with a neurological cause for abnormal detrusor activity
• Diabetic neuropathy
• 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
• Uncontrolled narrow angle glaucoma, urinary or gastric retention, colitis ulcerosa, toxic megacolon, myasthenia gravis or any other medical condition which in the opinion of the investigator makes the use of anticholinergics contra-indicated
• Non-drug treatment including electrostimulation therapy

(a bladder training program or pelvic floor exercises which started more than 1 month prior to entry into the study can be continued)

• Use of medications intended to treat urinary incontinence or listed in Appendix 1 Part A. Part B lists medications that are restricted but accepted under certain conditions
• Known or suspected hypersensitivity to tolterodine, other anticholinergics, ß-adrenoceptor agonists, or lactose or any of the other inactive ingredients
• Any clinically significant cardiovascular complication including CVA, recent myocardial infarction and uncontrolled hypertension, indicated by a sitting systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg
• Any clinically significant condition, which in the opinion of the investigator makes the patient unsuitable for the trial
• Participation in any clinical trial within 30 (90 in the UK) days prior to randomization
• Employees of the sponsor, third parties associated with the study, or the study site

At randomization:

• Patient who did not complete the micturition diary according to the instructions
• Average total daily urine volume > 3000 ml as recorded in the micturition diary
• Clinically significant elevation of serum creatinine or liver enzymes as evidenced by creatinine >150 mmol/L, ASAT or ALAT > 2x upper limit of normal range (ULN), γ-GT > 3x ULN and/or abnormal serum total bilirubin (as assessed in visit 1 samples or alternative sampling within 4 weeks prior to visit 1)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Oral	Drug: Placebo; Oral
Experimental: YM178 Dose 1; low dose	Drug: YM178; Oral; Other Names: mirabegron
Experimental: YM178 Dose 2; high dose	Drug: YM178; Oral; Other Names: mirabegron
Active Comparator: Tolterodine; Oral	Drug: tolterodine; Oral; Other Names: Detrusitol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in mean number of micturitions per 24 hours	Baseline and 4 weeks (end of treatment)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in mean number of urgency episodes/24 hours	Baseline and 4 weeks (end of treatment)
Change from baseline in mean volume voided per micturition	Baseline and 4 weeks (end of treatment)
Change from baseline in mean number of urge incontinence episodes/24 hours	Baseline and 4 weeks (end of treatment)
Change from baseline in mean number of incontinence episodes/24 hours	Baseline and 4 weeks (end of treatment)

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.
• Investigators: Study Director: Clinical Study Manager, Astellas Pharma Europe B.V.

Publications and helpful links

General Publications

• Chapple CR, Amarenco G, Lopez Aramburu MA, Everaert K, Liehne J, Lucas M, Vik V, Ridder A, Snijder R, Yamaguchi O; BLOSSOM Investigator Group. A proof-of-concept study: mirabegron, a new therapy for overactive bladder. Neurourol Urodyn. 2013 Nov;32(8):1116-22. doi: 10.1002/nau.22373. Epub 2013 Feb 19.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2004
• Primary Completion (Actual): January 25, 2005
• Study Completion (Actual): January 25, 2005

Study Registration Dates

• First Submitted: May 22, 2012
• First Submitted That Met QC Criteria: May 22, 2012
• First Posted (Estimated): May 24, 2012

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Urinary incontinence; Overactive Bladder; Mirabegron; YM178; Urgency; Frequency; Micturition; Urinary urge incontinence
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder Diseases; Urinary Bladder, Overactive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Adrenergic Agonists; Adrenergic Agents; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Urological Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Tolterodine Tartrate; Mirabegron
• Other Study ID Numbers: 178-CL-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR