Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Older Adult Subjects With Overactive Bladder (OAB)

NCT ID: NCT02216214

Last Updated: 2024-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 888 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-07
• Study Completion Date: 2018-01-02

Brief Summary

The purpose of this study was to assess the efficacy, safety and tolerability of mirabegron versus placebo in the treatment of older adult subjects with OAB.

Conditions

Overactive Bladder (OAB)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Participants received placebo to match mirabegron at an initial dose of 25 mg and may have been increased to 50 mg of matching placebo based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

oral tablet

Mirabegron

Participants received mirabegron at an initial dose of 25 mg and may have been increased to 50 mg mirabegron after 4 weeks or 8 weeks based on individual participant efficacy, tolerability and investigator discretion. Once a participant had increased dose, they remained on that dose for the remainder of the study unless there were safety reasons that required discontinuation of study drug.

Group Type: EXPERIMENTAL

Mirabegron

Intervention Type: DRUG

oral tablet

Interventions

Mirabegron

oral tablet

Intervention Type: DRUG

Placebo

oral tablet

Intervention Type: DRUG

Other Intervention Names

YM178; Myrbetriq

Eligibility Criteria

Inclusion Criteria

• Subject is willing and able to complete the micturition diary and questionnaires correctly.
• Subject has symptoms of wet overactive bladder (OAB) (urinary frequency and urgency with incontinence) for greater than or equal to 3 months prior to Screening.
• Subject agrees not to participate in another interventional study from the time of screening until the final study visit.

• Subjects must experience at least one incontinence episode in the placebo run-in period based on the 3-day micturition diary.
• Subject must experience at least 3 episodes of urgency (grade 3 or 4) based on the 3-day micturition diary.
• Subject must experience an average of greater than or equal to 8 micturitions/day based on the 3-day micturition diary.

Exclusion Criteria

• Subject has ongoing symptoms suggestive of bladder outlet obstruction (BOO) or history of BOO that is currently not well controlled.
• Subject has Post-Void Residual Volume (PVR) greater than 150 mL.
• Subject has neurogenic bladder or neurological dysfunction or injury which could affect the lower urinary tract or nerve supply.
• Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the Investigator (for female subjects confirmed by a cough provocation test). Subjects with a history of stress incontinence that is currently treated (e.g. remote history of surgery for stress incontinence) may be included as long as they pass cough provocation test.
• Subject has an indwelling catheter or practices intermittent self-catheterization.
• Subject has evidence of Urinary Tract Infection (UTI). Urine culture and sensitivity will be performed for positive leukocytes, or nitrites, or turbidity, or at the investigator's discretion and will be confirmed with a culture greater than 100,000 cfu/mL. If a subject has a UTI at Screening (Visit 1), the subject can be rescreened after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture).
• Subject has a chronic inflammatory condition such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs (i.e., within the confines of the pelvis including the bladder and rectum in both sexes and the uterus, ovaries, and fallopian tubes in females; organs of the lower gastrointestinal tract are not necessarily considered pelvic organs as the distal ascending colon, the full transverse colon and proximal portion of the descending colon are in the abdomen).
• Subject resides in a nursing home.
• Subject is likely to enter a hospital or nursing home due to medical instability within the next 6 months in the opinion of the Investigator.
• Subject has received intravesical injection in the past 12 months with botulinum toxin, resiniferatoxin, or capsaicin.
• Subject has received electro-stimulation therapy for OAB (e.g. sacral nerve stimulation or Percutaneous Tibial Nerve Stimulation [PTNS]).
• Subject began or has changed a bladder training program or pelvic floor exercises less than 30 days prior to Screening.
• Subject has moderate or severe hepatic impairment defined as Child-Pugh Class B or C.
• Subject has severe renal impairment defined as estimated creatinine clearance less than 29 mL/min determined by Estimated Glomerular Filtration Rate (eGFR, Cockroft-Gault, or MDRD formulae). A subject with end stage renal disease or undergoing dialysis is also not a candidate for the study.
• Subject has severe uncontrolled hypertension, which is defined as a sitting systolic blood pressure greater than or equal to 180 mmHg and/or diastolic blood pressure greater than or equal to 110 mmHg.
• Subject has evidence of QT prolongation on electrocardiogram (ECG) defined as QTc greater than 450 msec for males, QTc greater than 470 msec for females or a known history of QT prolongation.
• Subject has a clinically significant ECG abnormality, as determined by the Investigator.
• Subject has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2x upper limit of normal (ULN), or γ-GT greater than 3x ULN and considered clinically significant by the Investigator.
• Subject has a hypersensitivity to any components of mirabegron, other β-AR agonists, or any of the inactive ingredients.
• Subject has any clinically significant condition, which in the opinion of the Investigator makes the subject unsuitable for study participation.
• Subject has been treated with an experimental device within 28 days or received an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Screening.
• Subject has a concurrent malignancy or history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
• Subject with current history of alcohol and/or drug abuse.
• Subject is using prohibited medications which cannot be stopped safely during the period.
• Subject has stopped, started or changed the dose of a restricted medication within the last 30 days prior to Screening.
• Subject is involved in the conduct of the study as an employee of the Astellas group, third party associated with the study, or the study site team.
• Subject has previously received mirabegron.

• Subject was non-compliant during 2-week placebo run-in period, defined as taking less than 80% or greater than 120% of study medication.
• Subject has any systolic blood pressure measurement > 180 mmHg or diastolic blood pressure measurement > 110 in the 3-day diary or during the baseline visit.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc., Medical Affairs, Americas

Locations

Site US00066

Huntsville, Alabama, United States

Site US00148

Mobile, Alabama, United States

Site US00009

Anchorage, Alaska, United States

Site US00020

Tucson, Arizona, United States

Site US00019

Tucson, Arizona, United States

Site US00063

Little Rock, Arkansas, United States

Site US00081

Little Rock, Arkansas, United States

Site US00176

Anaheim, California, United States

Site US00048

Beverly Hills, California, United States

Site US00142

Beverly Hills, California, United States

Site US00150

Hawaiian Gardens, California, United States

Site US00112

Los Angeles, California, United States

Site US00034

Los Angeles, California, United States

Site US00010

Murrieta, California, United States

Site US00135

San Diego, California, United States

Site US00139

San Diego, California, United States

Site US00144

Santa Maria, California, United States

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Stanford, California, United States

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Colorado Springs, Colorado, United States

Site US00039

Denver, Colorado, United States

Site US00004

Denver, Colorado, United States

Site US00040

New London, Connecticut, United States

Site US00090

Washington D.C., District of Columbia, United States

Site US00064

Brooksville, Florida, United States

Site US00080

Coral Gables, Florida, United States

Site US00002

DeBary, Florida, United States

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DeLand, Florida, United States

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DeLand, Florida, United States

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Edgewater, Florida, United States

Site US00027

Fleming Island, Florida, United States

Site US00151

Hialeah, Florida, United States

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Jupiter, Florida, United States

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Kissimmee, Florida, United States

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Lakeland, Florida, United States

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Miami, Florida, United States

Site US00029

Miami, Florida, United States

Site US00042

Miami, Florida, United States

Site US00007

North Miami, Florida, United States

Site US00021

Pompano Beach, Florida, United States

Site US00035

Port Orange, Florida, United States

Site US00075

St. Petersburg, Florida, United States

Site US00099

Tampa, Florida, United States

Site US00005

Savannah, Georgia, United States

Site US00041

Boise, Idaho, United States

Site US00060

Greenwood, Indiana, United States

Site US00046

Jeffersonville, Indiana, United States

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West Des Moines, Iowa, United States

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Augusta, Kansas, United States

Site US00105

Newton, Kansas, United States

Site US00045

Overland Park, Kansas, United States

Site US00172

Lake Charles, Louisiana, United States

Site US00025

Annapolis, Maryland, United States

Site US00091

Brockton, Massachusetts, United States

Site US00006

New Bedford, Massachusetts, United States

Site US00145

Watertown, Massachusetts, United States

Site US00056

Grand Rapids, Michigan, United States

Site US00003

Kalamazoo, Michigan, United States

Site US00093

Saginaw, Michigan, United States

Site US00024

Edina, Minnesota, United States

Site US00137

Sartell, Minnesota, United States

Site US00159

Billings, Montana, United States

Site US00070

Norfolk, Nebraska, United States

Site US00014

Las Vegas, Nevada, United States

Site US00113

East Brunswick, New Jersey, United States

Site US00111

New Brunswick, New Jersey, United States

Site US00140

Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Williamsville, New York, United States

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Charlotte, North Carolina, United States

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Concord, North Carolina, United States

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Greensboro, North Carolina, United States

Site US00161

Raleigh, North Carolina, United States

Site US00165

Wilmington, North Carolina, United States

Site US00166

Winston-Salem, North Carolina, United States

Site US00085

Fargo, North Dakota, United States

Site US00067

Akron, Ohio, United States

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Cincinnati, Ohio, United States

Site US00095

Cleveland, Ohio, United States

Site US00084

Mentor, Ohio, United States

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Middleburg Heights, Ohio, United States

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Norman, Oklahoma, United States

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Portland, Oregon, United States

Site US00180

Pittsburgh, Pennsylvania, United States

Site US00082

Moncks Corner, South Carolina, United States

Site US00162

Mt. Pleasant, South Carolina, United States

Site US00032

Bristol, Tennessee, United States

Site US00154

Chattanooga, Tennessee, United States

Site US00053

Franklin, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

Site US00131

Houston, Texas, United States

Site US00174

Hurst, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

Site US00044

Salt Lake City, Utah, United States

Site US00036

Salt Lake City, Utah, United States

Site US00023

West Jordan, Utah, United States

Site US00170

Newport News, Virginia, United States

Site US00086

Norfolk, Virginia, United States

Site US00167

Seattle, Washington, United States

Site US00098

Tacoma, Washington, United States

Site US00062

Madison, Wisconsin, United States

Site CA00130

Edmonton, Alberta, Canada

Site CA00074

Vancouver, British Columbia, Canada

Site CA00155

Brampton, Ontario, Canada

Site CA00123

Corunna, Ontario, Canada

Site CA00169

Greater Sudbury, Ontario, Canada

Site CA00126

Hamilton, Ontario, Canada

Site CA00118

London, Ontario, Canada

Site CA00116

Sarnia, Ontario, Canada

Site CA00168

Toronto, Ontario, Canada

Site CA00164

Lévis, Quebec, Canada

Site CA00158

Montreal, Quebec, Canada

Site CA00073

Point Claire, Quebec, Canada

Site CA00106

Point Claire, Quebec, Canada

Site CA00156

Sherbrooke, Quebec, Canada

Site CA00061

Sherbrooke, Quebec, Canada

Site CA00129

Québec, , Canada

Site CA00160

Québec, , Canada

Countries

United States; Canada

References

Herschorn S, Staskin D, Schermer CR, Kristy RM, Wagg A. Safety and Tolerability Results from the PILLAR Study: A Phase IV, Double-Blind, Randomized, Placebo-Controlled Study of Mirabegron in Patients >/= 65 years with Overactive Bladder-Wet. Drugs Aging. 2020 Sep;37(9):665-676. doi: 10.1007/s40266-020-00783-w.

Reference Type: DERIVED

PMID: 32725584 (View on PubMed)

Griebling TL, Campbell NL, Mangel J, Staskin D, Herschorn S, Elsouda D, Schermer CR. Effect of mirabegron on cognitive function in elderly patients with overactive bladder: MoCA results from a phase 4 randomized, placebo-controlled study (PILLAR). BMC Geriatr. 2020 Mar 18;20(1):109. doi: 10.1186/s12877-020-1474-7.

Reference Type: DERIVED

PMID: 32183741 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://astellasclinicalstudyresults.com/study.aspx?ID=301

Link to results on Astellas Clinical Study Results website

Other Identifiers

178-MA-1005

Identifier Type: -

Identifier Source: org_study_id