Urge Incontinence, Urinary Incontinence, Urge
Conditions
Brief summary
An 8-week randomized, controlled, pilot clinical trial of Mirabegron compared to a standard anticholinergic therapy (Detrol LA) in elderly women with urgency urinary incontinence.
Interventions
DRUGMirabegron
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Community-dwelling, ambulatory females ≥ 65 years old * Urgency or Mixed Urgency Predominate Urinary Incontinence (subject-reported) for ≥ 3 months prior to Screening (Visit 1) * On a 3-day voiding diary, documentation of at least 3 urgency incontinence episodes with the number of urgency incontinence episodes greater than number of stress incontinence episodes * Capability of understanding and having signed the informed consent form after full discussion of the research nature of the treatment and its risk and benefits * Ability to perform all procedures and tests required by the protocol * Report having a primary health care provider * Willingness to remain on stable medication regime for duration of the randomized controlled trial. Participants will be asked to not add new medications during the randomized controlled trial, such as diuretics and other medications which may affect their voiding pattern.
Exclusion criteria
* Seated blood pressure \>180/110 at Screening or Baseline * Physician diagnosis of dementia * Current use of dementia medications, debilitating or recent neurologic disease * Mini Mental State Examination (MMSE) score \<20 * History of urinary retention, gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe ulcerative colitis, toxic megacolon, fistula or a hole in your bladder or rectum, birth defect leading to urine leakage, and urine leakage starting in childhood * Clinically significant hepatic (Child Pugh B or greater) or renal (creatinin clearance \<30 mL/min or eGFR \<30 mL/min/1.73 m2) * Neurologic conditions such as stroke, multiple sclerosis, spinal cord injury, or Parkinson's disease. * Major cardiovascular even in the past 6 months (i.e., MI, unstable angina, hospitalization for chest pain) * Symptomatic pelvic organ prolapse defined as participant report of feeling or seeing a bulge outside the vagina within the past 3 months. * History of surgery for incontinence in the past 5 years, pelvic surgery the past 6 months (i.e., for prolapse or hysterectomy), intra-vesical therapy (botox), and/or bulk injections within the past 6 months. * A known history of interstitial cystitis or a significant pain component associated with OAB symptoms, uninvestigated hematuria, urogenital cancer, radiation to the pelvis or external genitalia. * Urinary tract infection (UTI) as shown by the results of the urinalysis at screening or recurrent urinary tract infection (RUTIs) defined as treatment for UTI \>3 times in the last year. * Urinary retention (post-void residual urine volume \>150 cc measured by Bladder scan at screening. * Use of any electrostimulation, bladder training, or pelvic floor exercises (with certified incontinence practitioners) within 4 weeks of Screening. * Received study medication in any previous mirabegron clinical trial. * Prior failure for either efficacy or tolerability of ≥ 2 OAB medications in the last year. (Failure: inadequate symptom control after two medications for a minimum of one month each.) * Has been treated within 2 weeks prior to Screening and/or is currently being treated with: * Any drug treatment for OAB * Any drugs with significant anticholinergic and antispasmodic effects (see exception for tricyclic antidepressants below) * Has started treatment with tricyclic antidepressants or estrogens within 4 weeks prior to Screening and/or is not on a stable dose. * Intermittent use or unstable dose of diuretics. Treatment with diuretics initiated within 2 weeks prior to baseline and/or is not on a stable dose is not permitted. * Treatment with potent CYP3A4 inhibitors, such as clarithromycin, ketoconazole, and itraconazole within 2 weeks prior to Screening. * Administration of medications capable of inducing hepatic enzyme metabolism or transport (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John's Wort) in the past 30 days. * Administration of narrow therapeutic index drugs metabolized by CYP2D6, such as thioridazine, flecainide, and propafenone. * Previously received any investigational drug within 30 days prior to trial entry. * Alcohol and/or any other drug abuse in the opinion of the investigator. * Participants who have any medical (including known history of major hematological, renal, cardiovascular, or hepatic abnormalities) or psychological condition or social circumstances that would impair their ability to participate reliably in the trial, or those who may increase the risk to themselves or others by participating. * Participants who, in the opinion of the investigator, are not likely to complete the trial for whatever reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Completed and Discontinued the Study | Baseline to Week 8 | Feasibility - Assessment of retention rates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in California Verbal Learning Test (CVLT) Score at 8 Weeks | Baseline to Week 8 | Range of 0-80, with the higher the score the better. |
| Change From Baseline in Trail Making Test, Trail A Score at 8 Weeks | Baseline and 8 weeks | Trail Making Test, Trail A Time, Range 0-150 seconds, Lower score indicates better functioning |
| Change From Baseline in Short Physical Performance Battery (SPPB) Score at 8 Weeks | Baseline to Week 8 | Physical function/mobility, Range 0-12, the higher the score the better. |
| Change From Baseline in Total Urinary Incontinence Frequency Measured by a Voiding Diary at 8 Weeks | Baseline to Week 8 | Study participants record number of urinary incontinence episodes in a voiding diary. The total urinary incontinence frequency is the sum of urinary incontinence episodes per day. |
| Change From Baseline in Urge Incontinence Episodes Per Day on a Voiding Diary at 8 Weeks. | Baseline and 8 weeks | The sum of urge type incontinence episodes reported by participants on a voiding diary per day. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mirabegron Participants will be instructed to take one tablet and 1 capsule (total of 2) of blinded study medication once a day, orally, for 8 weeks. They will start with Mirabegron (25mg) dose of study medication and will have the option of dose escalation to 2 tablets and 2 capsules (total of 4) per day (Mirabegron 50mg).
Mirabegron | 12 |
| Tolterodine Tartrate Participants will be instructed to take one tablet and 1 capsule (total of 2) of blinded study medication once a day, orally, for 8 weeks. They will start with tolterodine tartrate (4 mg) dose of study medication and will have the option of dose escalation to 2 tablets and 2 capsules (total of 4) per day tolterodine tartrate 4 mg + identical placebo.
Tolterodine Tartrate | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Does not like/could not tolerate medicat | 0 | 1 |
| Overall Study | No improvement in symptoms | 1 | 0 |
Baseline characteristics
| Characteristic | Mirabegron | Tolterodine Tartrate | Total |
|---|---|---|---|
| Age, Customized 65-69 years | 5 Participants | 7 Participants | 12 Participants |
| Age, Customized 70-79 years | 7 Participants | 3 Participants | 10 Participants |
| Age, Customized 80-89 years | 0 Participants | 1 Participants | 1 Participants |
| California Verbal Learning Test | 51.36 Trials 1-5 Free Recall Total STANDARD_DEVIATION 12.29 | 49.50 Trials 1-5 Free Recall Total STANDARD_DEVIATION 10.98 | 50.48 Trials 1-5 Free Recall Total STANDARD_DEVIATION 11.43 |
| Incontinence Frequency Total Urge Incontinence | 3.87 Episodes per day STANDARD_DEVIATION 2.33 | 4.48 Episodes per day STANDARD_DEVIATION 1.92 | 4.16 Episodes per day STANDARD_DEVIATION 2.11 |
| Incontinence Frequency Total Urinary Incontinence | 4.43 Episodes per day STANDARD_DEVIATION 3.2 | 4.96 Episodes per day STANDARD_DEVIATION 1.98 | 4.68 Episodes per day STANDARD_DEVIATION 2.64 |
| Instrumental Activities of Daily Living | 7.83 score on scale STANDARD_DEVIATION 0.4 | 7.91 score on scale STANDARD_DEVIATION 0.3 | 7.87 score on scale STANDARD_DEVIATION 0.3 |
| Race/Ethnicity, Customized African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian or Asian American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latina | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latina | 11 Participants | 11 Participants | 22 Participants |
| Race/Ethnicity, Customized Other Race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 11 Participants | 10 Participants | 21 Participants |
| Region of Enrollment United States | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Short Physical Performance Battery | 10.67 Score on Scale STANDARD_DEVIATION 2.1 | 11.00 Score on Scale STANDARD_DEVIATION 2.2 | 10.83 Score on Scale STANDARD_DEVIATION 2.1 |
| Trail Making Test Trail A Time (0-150 sec) | 40.33 seconds STANDARD_DEVIATION 26.3 | 35.06 seconds STANDARD_DEVIATION 9.5 | 37.81 seconds STANDARD_DEVIATION 19.9 |
| Trail Making Test Trail B Time (0-300 sec) | 93.03 seconds STANDARD_DEVIATION 61.5 | 85.39 seconds STANDARD_DEVIATION 29.4 | 89.38 seconds STANDARD_DEVIATION 47.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 5 / 12 | 6 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
The Number of Participants Who Completed and Discontinued the Study
Feasibility - Assessment of retention rates.
Time frame: Baseline to Week 8
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mirabegron | The Number of Participants Who Completed and Discontinued the Study | Completed study | 11 Participants |
| Mirabegron | The Number of Participants Who Completed and Discontinued the Study | Discontinued Early | 1 Participants |
| Tolterodine Tartrate | The Number of Participants Who Completed and Discontinued the Study | Completed study | 10 Participants |
| Tolterodine Tartrate | The Number of Participants Who Completed and Discontinued the Study | Discontinued Early | 1 Participants |
p-value: 0.949ANCOVA
Secondary
Change From Baseline in California Verbal Learning Test (CVLT) Score at 8 Weeks
Range of 0-80, with the higher the score the better.
Time frame: Baseline to Week 8
Population: Although 21 participants completed week 8 visits in some form, some participants declined to complete or had missing data for one or more outcome measures at this timepoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mirabegron | Change From Baseline in California Verbal Learning Test (CVLT) Score at 8 Weeks | 4.70 Score on a Scale |
| Tolterodine Tartrate | Change From Baseline in California Verbal Learning Test (CVLT) Score at 8 Weeks | 1.59 Score on a Scale |
p-value: 0.241595% CI: [-2.09, 8.31]ANCOVA
Secondary
Change From Baseline in Short Physical Performance Battery (SPPB) Score at 8 Weeks
Physical function/mobility, Range 0-12, the higher the score the better.
Time frame: Baseline to Week 8
Population: Although 21 participants completed week 8 visits in some form, some participants declined to complete or had missing data for one or more outcome measures at this timepoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mirabegron | Change From Baseline in Short Physical Performance Battery (SPPB) Score at 8 Weeks | -0.39 score on a scale |
| Tolterodine Tartrate | Change From Baseline in Short Physical Performance Battery (SPPB) Score at 8 Weeks | 0.24 score on a scale |
p-value: 0.195695% CI: [-1.59, 0.33]ANCOVA
Secondary
Change From Baseline in Total Urinary Incontinence Frequency Measured by a Voiding Diary at 8 Weeks
Study participants record number of urinary incontinence episodes in a voiding diary. The total urinary incontinence frequency is the sum of urinary incontinence episodes per day.
Time frame: Baseline to Week 8
Population: Although 21 participants completed week 8 visits in some form, some participants declined to complete or had missing data for one or more outcome measures at this timepoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mirabegron | Change From Baseline in Total Urinary Incontinence Frequency Measured by a Voiding Diary at 8 Weeks | -2.04 episodes per day |
| Tolterodine Tartrate | Change From Baseline in Total Urinary Incontinence Frequency Measured by a Voiding Diary at 8 Weeks | -3.91 episodes per day |
p-value: 0.016895% CI: [0.34, 3.4]ANCOVA
Secondary
Change From Baseline in Trail Making Test, Trail A Score at 8 Weeks
Trail Making Test, Trail A Time, Range 0-150 seconds, Lower score indicates better functioning
Time frame: Baseline and 8 weeks
Population: Although 21 participants completed week 8 visits in some form, some participants declined to complete or had missing data for one or more outcome measures at this timepoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mirabegron | Change From Baseline in Trail Making Test, Trail A Score at 8 Weeks | -11.34 seconds |
| Tolterodine Tartrate | Change From Baseline in Trail Making Test, Trail A Score at 8 Weeks | 0.67 seconds |
p-value: 0.000195% CI: [-18.16, -5.87]ANCOVA
Secondary
Change From Baseline in Urge Incontinence Episodes Per Day on a Voiding Diary at 8 Weeks.
The sum of urge type incontinence episodes reported by participants on a voiding diary per day.
Time frame: Baseline and 8 weeks
Population: Although 21 participants completed week 8 visits in some form, some participants declined to complete or had missing data for one or more outcome measures at this timepoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mirabegron | Change From Baseline in Urge Incontinence Episodes Per Day on a Voiding Diary at 8 Weeks. | -1.64 episodes per day |
| Tolterodine Tartrate | Change From Baseline in Urge Incontinence Episodes Per Day on a Voiding Diary at 8 Weeks. | -3.74 episodes per day |
p-value: 0.010195% CI: [0.5, 3.71]ANCOVA