Study to Evaluate the Efficacy, Safety, and Tolerability of Mirabegron in Older Adult Subjects With Overactive Bladder (OAB)
- Registration Number
- NCT02216214
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 888
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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. Mirabegron 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.
- Primary Outcome Measures
Name Time Method Change From Baseline to End of Treatment (EOT) in Mean Number of Micturitions Per 24 Hours Baseline and EOT (up to 12 weeks) A micturition was defined as any voluntary act of passing urine (excluding incontinence only episodes). The mean number of micturitions per 24 hours was calculated as the average number of times a participant urinated per day during the 3-day micturition diary period.
Change From Baseline to EOT in Mean Number of Incontinence Episodes Per 24 Hours Baseline and EOT (up to 12 weeks) An incontinence episode was defined as the complaint of any involuntary leakage of urine. The mean number of incontinence episodes per 24 hours was calculated as the average number of times a participant recorded an incontinence episode per day during the 3-day micturition diary period.
- Secondary Outcome Measures
Name Time Method Change From Baseline to EOT in Overactive Bladder Questionnaire (OAB-q): Symptom Bother Score Baseline and EOT (up to 12 weeks) The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The symptom bother portion consists of 8 questions, rated on a 6-point Likert scale (1 through 6). The total symptom bother score was calculated from the 8 answers and then transformed to range from 0 (least severity) to 100 (worst severity). A negative change from baseline indicated an improvement.
Change From Baseline to EOT in Patient Perception of Bladder Condition (PPBC) Baseline and EOT (up to 12 weeks) The PPBC is a validated, global assessment tool using a 6-point Likert scale that asks participants to rate their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. A higher score indicated a worse perception of bladder condition.
Change From Baseline to EOT in Mean Volume Voided Per Micturition Baseline and EOT (up to 12 weeks) The mean volume voided per micturition during 3 days of the 3-day micturition diary period.
Change From to EOT in Mean Number of Nocturia Episodes Per 24 Hours Baseline and EOT (up to 12 weeks) A nocturia episode was defined as waking at night one or more time to void (i.e., any voiding associated with sleep disturbance between the date/time the participant goes to bed with the intention to sleep until the date/time the participant gets up in the morning with the intention to stay awake). A night time episode of incontinence only is not considered a nocturia episode. The mean number of nocturia episodes per 24 hours was calculated as the average number of times a participant recorded a nocturia episode per day during the 3-day micturition diary period.
Change From Baseline to EOT in Barthel Index of Daily Living Score Baseline and EOT (up to 12 weeks) The Barthel Index consists of 10 items that measure a person's daily functioning; specifically the activities of daily living and mobility. The total possible score ranges from 0 to 20, with lower scores indicating increased disability.
Change From Baseline in Number of Pads During 3-Day Diary Prior to Each Visit Baseline and EOT (up to 12 weeks) The number of pads were calculated as the number of times a participant records a new pad used during the 3-day micturition diary period. No data were collected for the number of pads used due to a failure in the programming of the diary used for data collection.
Change From Baseline to EOT in OAB-q: Health Related Quality of Life (HRQL) Total Score Baseline and EOT (up to 12 weeks) The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The total score was calculated by adding the 4 HRQoL subscale scores and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Change From Baseline to EOT in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours Baseline and EOT (up to 12 weeks) Urgency was defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. An urgency episode was defined as any micturition or incontinence episode with a severity of grade 3 or 4, assessed by participants based on the PPIUS, where 0 = No urgency; 1 = Mild urgency; 2 = Moderate urgency, could delay voiding a short while; 3 = Severe urgency, could not delay voiding; 4 = Urge incontinence, leaked before arriving to the toilet. The mean number of urgency episodes (grade 3 and/or 4) per 24 hours was calculated as the average number of times a participant recorded an urgency episode (grade 3 and/or 4) with or without incontinence per day during the 3-day micturition diary period.
Change From Baseline to EOT in Mean Number of Urgency Incontinence Episodes Per 24 Hours Baseline and EOT (up to 12 weeks) An urgency incontinence episode was defined as the involuntary leakage of urine accompanied by or immediately preceded by urgency. The mean number of urgency episodes was calculated as the average number of times a participant recorded an urgency incontinence episode per day during the 3-day micturition diary period.
Percentage of Participants With 50% Reduction in Mean Number of Incontinence Episodes Per 24 Hours End of treatment (up to 12 weeks) An incontinence episode was defined as the complaint of any involuntary leakage of urine. Participants with 50% reduction in mean number of incontinence episodes per 24 hours were defined as participants with at least 50% decrease from baseline in mean number of incontinence episodes per 24 hours during the treatment period at each visit.
Percentage of Participants With ≥ 1-Point Improvement From Baseline in PPBC End of treatment (up to 12 weeks) The PPBC is a validated, global assessment tool using a 6-point Likert scale that asks participants to rate their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. A higher score indicated a worse perception of bladder condition. Participants with ≥ 1-point improvement from baseline in PPBC were defined as participants with at least 1-point improvement from baseline in PPBC at each visit.
Change From Baseline to EOT in Vulnerable Elder Survey-13 (VES-13) Score Baseline and EOT (up to 12 weeks) The VES-13 is a simple function-based tool for screening community-dwelling populations to identify older persons at risk for health deterioration. The VES-13 considers age, self-related health, limitation in physical function, and functional disabilities. The total possible score ranges from 0 to 10, with higher scores indicating increased disability.
Change From Baseline to EOT in PPIUS Baseline and EOT (up to 12 weeks) The PPIUS is a 5-point categorical scale used by participants to rate the degree of associated urgency for each micturition and/or incontinence episode they experienced. categories include: 0 - No urgency, I felt no need to empty my bladder, but did so for other reasons; 1 - Mild urgency, I could postpone voiding as long as necessary, without fear of wetting myself; 2 - Moderate urgency, I could postpone voiding for a short while, without fear of wetting myself; 3 - Severe urgency, I could not postpone voiding, but had to rush to the toilet in order not to wet myself; 4 - Urge incontinence, I leaked before arriving at the toilet. Scores were recorded in the micturition diary.
Change From Baseline to EOT in Treatment Satisfaction Visual Analog Scale (TS-VAS) Baseline and EOT (up to 12 weeks) The TS-VAS is a visual analog scale that asks participants to rate their satisfaction with the treatment by placing a vertical mark on a line that runs from 0 (No, not at all) to 100 (Yes, completely).
Change From Baseline in Number of Incontinence Episodes Reported During 3-Day Diary Prior to Each Visit Baseline and Weeks 4, 8 and EOT (up to 12 weeks) An incontinence episode was defined as the complaint of any involuntary leakage of urine. The number of incontinence episodes were calculated as the total number of the incontinence episodes recorded during the 3-day micturition diary period.
Percentage of Participants With Zero Incontinence Episodes Per 24 Hours End of treatment (up to 12 weeks) An incontinence episode was defined as the complaint of any involuntary leakage of urine. Participants with zero incontinence episodes per 24 hours were defined as participants who had no incontinence episodes per 24 hours during the treatment period at each visit.
Change From Baseline to EOT in OAB-q HRQL Subscale Scores Baseline and EOT (up to 12 weeks) The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The Coping score has 8 items, the Concern score has 7 items, the Sleep and Social score has 5 items each. Each subscale score was calculated by adding each score's items and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. A positive change from baseline indicated an improvement.
Percentage of Participants Who Achieved Micturition Frequency Normalization End of treatment (up to 12 weeks) Participants who achieved micturition frequency normalization were defined as participants who had at least 8 micturitions per 24 hours at baseline and less than 8 micturitions per 24 hours post-baseline.
Change From Baseline to EOT in Montreal Cognitive Assessment (MoCA) Score Baseline and EOT (up to 12 weeks) The MoCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total possible score is 30 points, with lower scores indicating worse cognitive function.
Change From Baseline in Post-void Residual Volume (PVR) Baseline and EOT (up to 12 weeks) PVR was assessed by ultrasonography or bladder scan.
Change From Baseline to EOT in University of Alabama, Birmingham - Life Space Assessment (UAB-LSA) Baseline and EOT (up to 12 weeks) The UAB-LSA measures mobility in terms of the spatial extent of a person's life. Life space is defined based upon the distance a person routinely travels to perform activities over this time frame. The UAB-LSA includes determining how far and how often the person leaves his or her place of residence and the degree of independence the person has. Each level of life space represents a distance further from the room where one sleeps: 0 - Mobility limited to the room where one sleeps; 1 - Mobility limited to within one's dwelling; 2 - Mobility limited to the space just proximal to one's personal living space (for instance, a porch, patio, or yard just outside the home or hallway outside of an apartment); 3 - Mobility limited to one's neighborhood; 4 - Mobility limited to one's town; 5 - Mobility outside one's town. The total scores ranges from 0-120, where a higher score indicates greater mobility.
Percentage of Participants With ≥ 10-Point Improvement From Baseline in OAB-q HRQL Subscales End of treatment (up to 12 weeks) The OAB-q is a self-reported questionnaire with 33 questions relating to symptom bother and health-related quality of life (HRQoL). The HRQoL portion consists of 25 HRQoL items comprising 4 HRQoL subscales (Coping, Concern, Sleep, and Social Interaction), each item was scored 1-6. The Coping score has 8 items, the Concern score has 7 items, the Sleep and Social score has 5 items each. Each subscale score was calculated by adding each score's items and transforming to a scale from 0 to 100, with higher scores indicating better quality of life. Participants with ≥ 10-point improvement from baseline in OAB-q HRQL subscales were defined as participants with at least 10-point improvement from baseline in OAB-q Subscales at each visit.
Percentage of Participants Major (≥ 2-Point) Improvement From Baseline in PPBC End of treatment (up to 12 weeks) The PPBC is a validated, global assessment tool using a 6-point Likert scale that asks participants to rate their subjective impression of their current bladder condition. Participants assessed their bladder condition using this scale: 1. Does not cause me any problems at all; 2. Causes me some very minor problems; 3. Causes me some minor problems; 4. Causes me (some) moderate problems; 5. Causes me severe problems; 6. Causes me many severe problems. A higher score indicated a worse perception of bladder condition. Participants with ≥ 2-point improvement from baseline in PPBC were defined as participants with at least 1-point improvement from baseline in PPBC at each visit.
Number of Participants With Adverse Events (AEs) From first dose of study drug up to 30 days after last dose of study drug (up to 13 weeks) Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. AEs were considered as serious if resulted in in death, was life-threatening resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly or birth defect, required inpatient hospitalization or led to prolongation of hospitalization and other medically important events.
Trial Locations
- Locations (120)
Site US00102
🇺🇸Norman, Oklahoma, United States
Site US00122
🇺🇸Greensboro, North Carolina, United States
Site US00112
🇺🇸Los Angeles, California, United States
Site US00025
🇺🇸Annapolis, Maryland, United States
Site CA00160
🇨🇦Quebec, Canada
Site CA00129
🇨🇦Quebec, Canada
Site CA00156
🇨🇦Sherbrooke, Quebec, Canada
Site US00037
🇺🇸Miami, Florida, United States
Site US00042
🇺🇸Miami, Florida, United States
Site US00180
🇺🇸Pittsburgh, Pennsylvania, United States
Site US00131
🇺🇸Houston, Texas, United States
Site US00167
🇺🇸Seattle, Washington, United States
Site US00068
🇺🇸San Antonio, Texas, United States
Site US00071
🇺🇸San Antonio, Texas, United States
Site US00044
🇺🇸Salt Lake City, Utah, United States
Site US00066
🇺🇸Huntsville, Alabama, United States
Site US00148
🇺🇸Mobile, Alabama, United States
Site US00176
🇺🇸Anaheim, California, United States
Site US00019
🇺🇸Tucson, Arizona, United States
Site US00142
🇺🇸Beverly Hills, California, United States
Site US00048
🇺🇸Beverly Hills, California, United States
Site US00150
🇺🇸Hawaiian Gardens, California, United States
Site US00034
🇺🇸Los Angeles, California, United States
Site US00010
🇺🇸Murrieta, California, United States
Site US00135
🇺🇸San Diego, California, United States
Site US00144
🇺🇸Santa Maria, California, United States
Site US00139
🇺🇸San Diego, California, United States
Site US00083
🇺🇸Stanford, California, United States
Site US00026
🇺🇸Colorado Springs, Colorado, United States
Site US00090
🇺🇸Washington, District of Columbia, United States
Site US00064
🇺🇸Brooksville, Florida, United States
Site US00080
🇺🇸Coral Gables, Florida, United States
Site US00002
🇺🇸DeBary, Florida, United States
Site US00001
🇺🇸DeLand, Florida, United States
Site US00017
🇺🇸DeLand, Florida, United States
Site US00027
🇺🇸Fleming Island, Florida, United States
Site US00018
🇺🇸Edgewater, Florida, United States
Site US00151
🇺🇸Hialeah, Florida, United States
Site US00057
🇺🇸Kissimmee, Florida, United States
Site US00179
🇺🇸Jupiter, Florida, United States
Site US00076
🇺🇸Lakeland, Florida, United States
Site US00029
🇺🇸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
🇺🇸Saint Petersburg, Florida, United States
Site US00005
🇺🇸Savannah, Georgia, United States
Site US00060
🇺🇸Greenwood, Indiana, United States
Site US00046
🇺🇸Jeffersonville, Indiana, United States
Site US00134
🇺🇸West Des Moines, Iowa, United States
Site US00104
🇺🇸Augusta, Kansas, United States
Site US00105
🇺🇸Newton, Kansas, United States
Site US00045
🇺🇸Overland Park, Kansas, United States
Site US00091
🇺🇸Brockton, Massachusetts, United States
Site US00006
🇺🇸New Bedford, Massachusetts, United States
Site US00145
🇺🇸Watertown, Massachusetts, United States
Site US00003
🇺🇸Kalamazoo, Michigan, United States
Site US00056
🇺🇸Grand Rapids, Michigan, United States
Site US00093
🇺🇸Saginaw, Michigan, United States
Site US00024
🇺🇸Edina, Minnesota, United States
Site US00137
🇺🇸Sartell, Minnesota, United States
Site US00016
🇺🇸Brooklyn, New York, United States
Site US00043
🇺🇸Williamsville, New York, United States
Site US00153
🇺🇸Charlotte, North Carolina, United States
Site US00132
🇺🇸Concord, North Carolina, United States
Site US00161
🇺🇸Raleigh, North Carolina, United States
Site US00085
🇺🇸Fargo, North Dakota, United States
Site US00067
🇺🇸Akron, Ohio, United States
Site US00050
🇺🇸Cincinnati, Ohio, United States
Site US00095
🇺🇸Cleveland, Ohio, United States
Site US00084
🇺🇸Mentor, Ohio, United States
Site US00015
🇺🇸Middleburg Heights, Ohio, United States
Site US00082
🇺🇸Moncks Corner, South Carolina, United States
Site US00174
🇺🇸Hurst, Texas, United States
Site US00100
🇺🇸San Antonio, Texas, 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 US00098
🇺🇸Tacoma, Washington, United States
Site CA00074
🇨🇦Vancouver, British Columbia, Canada
Site CA00123
🇨🇦Corunna, Ontario, Canada
Site CA00155
🇨🇦Brampton, Ontario, Canada
Site CA00118
🇨🇦London, Ontario, Canada
Site CA00116
🇨🇦Sarnia, Ontario, Canada
Site CA00169
🇨🇦Sudbury, Ontario, Canada
Site CA00168
🇨🇦Toronto, Ontario, Canada
Site CA00164
🇨🇦Lévis, Quebec, Canada
Site CA00106
🇨🇦Point Claire, Quebec, Canada
Site US00039
🇺🇸Denver, Colorado, United States
Site US00004
🇺🇸Denver, Colorado, United States
Site US00103
🇺🇸Portland, Oregon, United States
Site US00081
🇺🇸Little Rock, Arkansas, United States
Site US00162
🇺🇸Mount Pleasant, South Carolina, United States
Site US00053
🇺🇸Franklin, Tennessee, United States
Site CA00061
🇨🇦Sherbrooke, Quebec, Canada
Site US00040
🇺🇸New London, Connecticut, United States
Site US00159
🇺🇸Billings, Montana, United States
Site US00020
🇺🇸Tucson, Arizona, United States
Site US00154
🇺🇸Chattanooga, Tennessee, United States
Site US00063
🇺🇸Little Rock, Arkansas, United States
Site US00172
🇺🇸Lake Charles, Louisiana, United States
Site US00052
🇺🇸Nashville, Tennessee, United States
Site CA00158
🇨🇦Montreal, Quebec, Canada
Site CA00073
🇨🇦Point Claire, Quebec, Canada
Site US00032
🇺🇸Bristol, Tennessee, United States
Site US00113
🇺🇸East Brunswick, New Jersey, United States
Site US00009
🇺🇸Anchorage, Alaska, United States
Site US00111
🇺🇸New Brunswick, New Jersey, United States
Site US00070
🇺🇸Norfolk, Nebraska, United States
Site US00014
🇺🇸Las Vegas, Nevada, United States
Site US00041
🇺🇸Boise, Idaho, United States
Site CA00126
🇨🇦Hamilton, Ontario, Canada
Site US00165
🇺🇸Wilmington, North Carolina, United States
Site US00099
🇺🇸Tampa, Florida, United States
Site US00175
🇺🇸Austin, Texas, United States
Site US00140
🇺🇸Albuquerque, New Mexico, United States
Site US00166
🇺🇸Winston-Salem, North Carolina, United States
Site US00062
🇺🇸Madison, Wisconsin, United States
Site CA00130
🇨🇦Edmonton, Alberta, Canada