Clinical trial NCT02216214: Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Older Adult Subjects With Overactive Bladder (OAB)
Official title: A Phase 4, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multi-Center Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Older Adult Subjects With Overactive Bladder (OAB)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Overactive Bladder (OAB)
Keywords: Urinary Incontinence
Mirabegron
Overactive Bladder
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-08-13
Enrollment: 888
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria assessed at Visit 1 (Screening):

* 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.

Inclusion Criteria assessed after placebo run-in period at Visit 3 (Baseline):

* Subject continues to meet all inclusion criteria of Visit 1.
* 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 assessed at Visit 1 (Screening):

* 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.

Exclusion Criteria assessed after placebo run-in period at Visit 3 (Baseline):

* Subject fulfills any exclusion criteria of Visit 1 (subject does not need to repeat screening assessments \[PVR, cough provocation test, chemistry/hematology/urinalysis\]).
* 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.

Primary outcomes:
measure: Change From Baseline to End of Treatment (EOT) in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and EOT (up to 12 weeks)
Secondary outcomes:
measure: Change From Baseline to EOT in Mean Volume Voided Per Micturition
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in OAB-q: Health Related Quality of Life (HRQL) Total Score
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in Patient Perception of Bladder Condition (PPBC)
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in Mean Number of Urgency Incontinence Episodes Per 24 Hours
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From to EOT in Mean Number of Nocturia Episodes Per 24 Hours
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in Barthel Index of Daily Living Score
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in Vulnerable Elder Survey-13 (VES-13) Score
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in PPIUS
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in OAB-q HRQL Subscale Scores
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in Treatment Satisfaction Visual Analog Scale (TS-VAS)
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline to EOT in University of Alabama, Birmingham - Life Space Assessment (UAB-LSA)
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline in Number of Incontinence Episodes Reported During 3-Day Diary Prior to Each Visit
timeFrame: Baseline and Weeks 4, 8 and EOT (up to 12 weeks)
measure: Change From Baseline in Number of Pads During 3-Day Diary Prior to Each Visit
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Percentage of Participants Who Achieved Micturition Frequency Normalization
timeFrame: End of treatment (up to 12 weeks)
measure: Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: End of treatment (up to 12 weeks)
measure: Percentage of Participants With Zero Incontinence Episodes Per 24 Hours
timeFrame: End of treatment (up to 12 weeks)
measure: Percentage of Participants With ≥ 10-Point Improvement From Baseline in OAB-q HRQL Subscales
timeFrame: End of treatment (up to 12 weeks)
measure: Percentage of Participants With ≥ 1-Point Improvement From Baseline in PPBC
timeFrame: End of treatment (up to 12 weeks)
measure: Percentage of Participants Major (≥ 2-Point) Improvement From Baseline in PPBC
timeFrame: End of treatment (up to 12 weeks)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (up to 13 weeks)
measure: Change From Baseline to EOT in Montreal Cognitive Assessment (MoCA) Score
timeFrame: Baseline and EOT (up to 12 weeks)
measure: Change From Baseline in Post-void Residual Volume (PVR)
timeFrame: Baseline and EOT (up to 12 weeks)
Other outcomes:
Locations:
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state: California
city: Beverly Hills
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state: California
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state: California
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state: California
city: Santa Maria
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state: California
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state: California
city: Colorado Springs
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state: Colorado
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state: Colorado
city: Denver
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state: Colorado
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state: Connecticut
city: Washington
country: United States
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state: District of Columbia
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state: Florida
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city: Houston
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city: San Antonio
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state: Texas
city: San Antonio
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city: San Antonio
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state: Texas
city: Salt Lake City
country: United States
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state: Utah
city: Salt Lake City
country: United States
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state: Utah
city: West Jordan
country: United States
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state: Utah
city: Newport News
country: United States
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state: Virginia
city: Norfolk
country: United States
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state: Virginia
city: Seattle
country: United States
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state: Washington
city: Tacoma
country: United States
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state: Washington
city: Madison
country: United States
facility: Site US00062
state: Wisconsin
city: Edmonton
country: Canada
facility: Site CA00130
state: Alberta
city: Vancouver
country: Canada
facility: Site CA00074
state: British Columbia
city: Brampton
country: Canada
facility: Site CA00155
state: Ontario
city: Corunna
country: Canada
facility: Site CA00123
state: Ontario
city: Hamilton
country: Canada
facility: Site CA00126
state: Ontario
city: London
country: Canada
facility: Site CA00118
state: Ontario
city: Sarnia
country: Canada
facility: Site CA00116
state: Ontario
city: Sudbury
country: Canada
facility: Site CA00169
state: Ontario
city: Toronto
country: Canada
facility: Site CA00168
state: Ontario
city: Lévis
country: Canada
facility: Site CA00164
state: Quebec
city: Montreal
country: Canada
facility: Site CA00158
state: Quebec
city: Point Claire
country: Canada
facility: Site CA00073
state: Quebec
city: Point Claire
country: Canada
facility: Site CA00106
state: Quebec
city: Sherbrooke
country: Canada
facility: Site CA00156
state: Quebec
city: Sherbrooke
country: Canada
facility: Site CA00061
state: Quebec
city: Quebec
country: Canada
facility: Site CA00129
city: Quebec
country: Canada
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Study officials:
affiliation: Astellas Pharma Global Development, Inc., Medical Affairs, Americas
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.