Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of Mirabegron (YM178) in Men With Lower Urinary Tract Symptoms (LUTS) and Bladder Outlet Obstruction (BOO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00410514
First received: December 12, 2006
Last updated: March 7, 2014
Last verified: September 2012
  Purpose

This study examined the safety, tolerability, and efficacy of mirabegron (YM178) compared to placebo.


Condition Intervention Phase
Lower Urinary Tract Symptoms
Bladder Outlet Obstruction
Drug: Mirabegron
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-blind, Parallel Group, Placebo Controlled, Multi-center Study to Evaluate the Urodynamics and Safety of YM178 in Male Subjects With Lower Urinary Tract Symptoms (LUTS) and Bladder Outlet Obstruction (BOO)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Change From Baseline to End of Treatment in Maximum Flow Rate (Qmax) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: Yes ]

    Maximum urinary flow rate (Qmax) was measured by the Investigator using cystometry and was sent to an independent central reading center for review and interpretation.

    Least squares means (LSM) were derived from an analysis of covariance (ANCOVA) model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to End of Treatment in Detrusor Pressure at Maximum Flow Rate (PdetQmax) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: Yes ]

    Detrusor pressure at maximum urinary flow rate (PdetQmax) was measured by the Investigator using cystometry and was sent to an independent central reading center for review and interpretation.

    Least squares means (LSM) were derived from an analysis of covariance (ANCOVA) model with the pooled study center and treatment as factors and the baseline value as a covariate.



Secondary Outcome Measures:
  • Change From Baseline to End of Treatment in Bladder Contractile Index (BCI) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: Yes ]

    The Bladder Contractile Index (BCI) is a value used to measure the degree of contractility. BCI was calculated using the following formula:

    BCI = pdetQmax + 5Qmax.

    Strong contractility is a BCI > 150, normal contractility is a BCI of 100-150 and weak contractility is a BCI of < 100.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to End of Treatment in Bladder Voiding Efficiency (BVE) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: Yes ]

    Bladder Voiding Efficiency (BVE) is a product of bladder contractility against the urethral resistance and is measured according to the degree of bladder emptying. BVE is expressed as a percentage and is calculated using the formula:

    Bladder Voiding efficiency = (Voided volume x 100)/maximum cystometric capacity.

    A higher number indicates a higher voiding efficiency. Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Postvoid Residual Volume (PVR) [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: Yes ]

    Healthy micturitions (urinations) result in complete emptying of the bladder. Post Void Residual (PVR) is the volume of urine retained after voiding and was assessed using abdominal ultrasound. An increasing PVR over time is an indicator of abnormal bladder function or detrusor decompensation.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Safety Assessed by Adverse Events (AEs), Electrocardiogram (ECG), Vital Signs, Physical Exam and Laboratory Tests [ Time Frame: From first dose to within 30 days after last dose of double blind study medication (up to 16 weeks). ] [ Designated as safety issue: No ]
    Abnormal laboratory parameters, vital signs or ECG data were defined as AEs if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A serious AE was an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, was life-threatening, required or prolonged hospitalization or was considered medically important. AEs were assessed by the Investigator for intensity as mild, moderate or severe and for causal relationship to study drug.

  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Total Score [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: No ]

    The IPSS is a validated global questionnaire used to assess the degree of "bother" from benign prostatic hyperplasia symptoms and is based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Voiding Score [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: No ]

    The IPSS is a validated global questionnaire used to assess the degree of "bother" from benign prostatic hyperplasia symptoms based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The voiding score is the sum of the responses to 4 questions relating to urination (incomplete emptying, intermittency, weak stream and straining) and ranges from 0 to 20 (asymptomatic to very symptomatic).

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in International Prostate Symptoms Score (IPSS) Storage Symptom Score [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: No ]

    The IPSS is a validated global questionnaire used to assess the degree of "bother" from benign prostatic hyperplasia symptoms based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity of the particular symptom. The storage symptom score is the sum of the responses to 3 questions relating to storage symptoms (frequency, urgency and nocturia) and ranges from 0 to 15 (asymptomatic to very symptomatic).

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Patient Perception of Bladder Condition (PPBC) [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: No ]

    The patient perception of bladder condition (PPBC) asks participants to assess their bladder condition using a 6-point validated Likert scale which ranges from 1 (does not cause me any problems at all) to 6 (causes me many severe problems).

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Micturitions Per 24 Hours [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: No ]

    A micturition is any voluntary urination, excluding episodes of incontinence only. The mean number of micturitions per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Urgency Episodes With Urgency Severity ≥ 3 Per 24 Hours [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: No ]

    For each micturition and/or incontinence episode in the 3 days preceding the clinic visit, participants rated the degree of associated urgency (the sudden compelling desire to pass urine, which is difficult to defer) according to the following scale: 0: No Urgency, felt no need to empty my bladder but did so for another reason; 1: Mild Urgency, could postpone passing water for as long as necessary; 2: Moderate Urgency, could postpone passing water for a short while; 3: Severe Urgency, could not postpone passing water; 4: Urge Incontinence, leaked before reaching the toilet.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: No ]

    The mean number of incontinence episodes (the involuntary leakage of urine) per 24 hours was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 1, 4, 8, 12 and End of Treatment in Mean Voided Volume Per Micturition [ Time Frame: Baseline and Weeks 1, 4, 8 and 12 ] [ Designated as safety issue: No ]

    The mean volume voided per micturition was calculated from data recorded by the participant in the micturition diary for the 3 days preceding each clinic visit.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 4, 8, 12 and End of Treatment in International Consultation on Incontinence Questionnaire - Male Lower Urinary Tract Symptom (ICIQ MLUTS) Total Symptom Score [ Time Frame: Baseline and Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]

    Male lower urinary tract symptoms were assessed by the ICIQ MaleLUTS questionnaire which consists of 13 questions each on a 0-4 scale (larger scores correspond to worse conditions). The total symptom score ranges from 0 to 52.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 4, 8, 12 and End of Treatment in International Consultation on Incontinence Questionnaire - Male Lower Urinary Tract Symptom (ICIQ MLUTS) Total Bother Score [ Time Frame: Baseline and Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]

    The degree to which urinary symptoms bothered participants was assessed by the ICIQ MaleLUTS questionnaire which consists of 13 symptom bother questions each on a 0-10 scale (larger scores correspond to worse outcomes). The total bother score ranges from 0 to 130.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 4, 8, 12 and End of Treatment in International Consultation on Incontinence Questionnaire - Lower Urinary Tract Symptom Quality of Life (ICIQ-LUTSqol) Symptom Score [ Time Frame: Baseline and Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]

    Quality of life was assessed by the ICIQ-LUTSqol questionnaire which consists of 19 questions each on a 1-4 scale (larger scores correspond to less quality of life). The total symptom score ranges from 19 - 76.

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.


  • Change From Baseline to Weeks 4, 8, 12 and End of Treatment in International Consultation on Incontinence Questionnaire - Lower Urinary Tract Symptom Quality of Life (ICIQ-LUTSqol) Overall Symptom Interference of Life Score [ Time Frame: Baseline and Weeks 4, 8 and 12 ] [ Designated as safety issue: No ]

    Participants were asked to rate how much their urinary symptoms interfered overall with their everyday life on a scale from 0 (not at all) to 10 (a great deal).

    Least squares means were derived from an ANCOVA model with the pooled study center and treatment as factors and the baseline value as a covariate.



Enrollment: 200
Study Start Date: December 2006
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants received matching mirabegron placebo tablets orally once daily for 12 weeks.
Drug: Placebo
oral
Experimental: Mirabegron 50 mg
Participants received 50 mg mirabegron tablets orally once daily for 12 weeks.
Drug: Mirabegron
oral
Other Names:
  • YM178
  • Myrbetriq
Experimental: Mirabegron 100 mg
Participants received 100 mg mirabegron tablets orally once daily for 12 weeks.
Drug: Mirabegron
oral
Other Names:
  • YM178
  • Myrbetriq

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men 45 years of age or older
  • Documented bladder outlet obstruction

Exclusion Criteria:

  • History of urinary retention
  • Symptomatic and recurrent urinary tract infection (UTI)
  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: NCT00410514

  Show 27 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Use Central Contact Astellas Pharma US, Inc.
  More Information

Publications:
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT00410514     History of Changes
Other Study ID Numbers: 178-CL-060
Study First Received: December 12, 2006
Results First Received: August 2, 2012
Last Updated: March 7, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Astellas Pharma Inc:
Beta-3 Receptor Agonist
YM178
Men
Lower Urinary Tract Symptoms
Bladder Outlet Obstruction

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

ClinicalTrials.gov processed this record on November 25, 2014