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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01604928
First received: May 22, 2012
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Urinary Bladder, Overactive
Drug: YM178
Drug: tolterodine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Parallel Group, Proof of Concept Study of YM178 in Comparison With Placebo and Tolterodine in Patients With Symptomatic Overactive Bladder

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Change from baseline in mean number of micturitions per 24 hours [ Time Frame: Baseline and 4 weeks (end of treatment) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in mean number of urgency episodes/24 hours [ Time Frame: Baseline and 4 weeks (end of treatment) ] [ Designated as safety issue: No ]
  • Change from baseline in mean volume voided per micturition [ Time Frame: Baseline and 4 weeks (end of treatment) ] [ Designated as safety issue: No ]
  • Change from baseline in mean number of urge incontinence episodes/24 hours [ Time Frame: Baseline and 4 weeks (end of treatment) ] [ Designated as safety issue: No ]
  • Change from baseline in mean number of incontinence episodes/24 hours [ Time Frame: Baseline and 4 weeks (end of treatment) ] [ Designated as safety issue: No ]

Enrollment: 260
Study Start Date: April 2004
Study Completion Date: January 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: YM178 Dose 1
low dose
Drug: YM178
Oral
Other Name: mirabegron
Experimental: YM178 Dose 2
high dose
Drug: YM178
Oral
Other Name: mirabegron
Active Comparator: Tolterodine Drug: tolterodine
Oral
Other Name: Detrusitol
Placebo Comparator: Placebo Drug: Placebo
Oral

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01604928

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

Additional Information:
No publications provided by Astellas Pharma Inc

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier: NCT01604928     History of Changes
Other Study ID Numbers: 178-CL-008
Study First Received: May 22, 2012
Last Updated: July 1, 2013
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Czech Republic: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Astellas Pharma Inc:
Overactive Bladder
Frequency
Micturition
Urgency
Urinary incontinence
Urinary urge incontinence
YM178
Mirabegron

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Tolterodine
Mirabegron
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 01, 2014