Parkinsons Disease
Conditions
Brief summary
The purpose of this study is to see if the study drug, Mirabegron, is safe and effective in treating symptoms of Overactive Bladder in people with Parkinson's Disease.
Detailed description
This study is a randomized 1:1 placebo-controlled 10-week study of Mirabegron as add-on therapy to an educational intervention of behavioral modification including pelvic floor exercise (PFE) in a cohort of 40 Parkinson's subjects over the age of 30 with overactive bladder (OAB). Active drug will be Mirabegron 25 mg daily with up-titration to 50 mg daily after 5 weeks. Subjects will be enrolled based on response to an overactive bladder questionnaire at visit 2. Enrolled subjects will have 4 study visits to the clinic as well as 2 phone visits. Enrolled subjects will be asked to record urinary symptoms and pelvic floor exercises in a diary at 3 separate time points for a 72 hour period.
Interventions
DRUGMirabegron
25 mg po daily for 32-40 days. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose.
DRUGPlacebo
Placebo 25 mg po daily. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose.
Sponsors
Astellas Pharma US, Inc.
Daniel Burdick, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
- * Diagnosis of Parkinsons by United Kingdom brain bank criteria * Age \> 30 years old * No change in Parkinsons medications during the 4 weeks preceding screening, with no dose changes during the study, except that PRN (as needed) doses of carbidopa/levodopa will be allowed to address periodic worsening of parkinsonian symptoms. * Patient willing and able to complete micturition diary * Urinary urgency (≥ 8 entries of bladder urgency score \> 2) in 72hr voiding diary during screening period * Micturition frequency ≥ 8 / 24hr or incontinence ≥ 2 episodes in 72hr voiding diary during screening period * Use of other medication that could influence bladder function, other than those specifically prohibited (see below), will be permitted as long as the dose is stable for 4 weeks preceding screening, with no dose changes during the study. * Patient expects to have valid health insurance for the duration of the study period
Exclusion criteria
* Women who are breast-feeding, pregnant or have potential to become pregnant during the course of the study (fertile and unwilling/unable to use effective contraceptive measures). * Cognitive deficits that in the opinion of the investigator would interfere with the subject's ability to give informed consent or perform study testing. * Screening blood pressure \> 165 systolic or 100 diastolic * Heart rate \> 100 * History of allergy to Mirabegron. * Screening post-void residual \> 200ml * Evidence of urinary tract infection at screening * History of chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs * Intravesical botulinum toxin treatment within the previous six months of screening. * Presence of Interstim device * Use of indwelling catheter or self-catheterization * Concurrent use of thioridazine, flecainide, propafenone, or Digoxin * Concurrent use of warfarin (Coumadin) * Use of one of the anti-cholinergic bladder medications specified below within 14 days of the screening visit. Subjects who have used one of these medications in the past but discontinued it at least 14 days prior to the screening visit can be enrolled. * Screening estimated glomerular filtration rate (eGFR) \< 60, AST ( aspartate aminotransferase ) or ALT ( alanine aminotransferase ) \> 2x upper limit of normal * Any other serious and/or unstable medical condition * Participation in other drug studies or use of other investigational drugs within 30 days prior to Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Mean Daily Overactive Bladder-Symptom Composite Score. | 7-82 days. From visit 2 (baseline) to visit 4 | The primary outcome measure will be the change in the mean daily Overactive Bladder-Symptom Composite Score (OAB-SCS) from baseline (visit 2) to visit 4. The Over active Bladder- Symptom Composite Score requires subjects to record the severity of urgency of each micturition over a 72 hour period. Subject ratings ranges from 1 to 6 for each micturition as follows: 1. Not at all, 2.A little bit, 3.Somewhat 4.Quite a bit, 5. A great deal, 6. A very great deal. Maximum score depends on number of micturition episodes in the 72 hour period, as the rating of each episode is summed to get the total score. Higher scores indicate worse symptoms of overactive bladder. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overactive Bladder Questionnaire Symptom Severity Scale( OAB-q) | baseline (7-14 days post visit 1), visit 3( 32-40 days post visit 2) and visit 4(74-82 days post visit 2) | Overactive Bladder questionnaire symptom severity scale (OAB-q), Visit 3 and Visit 4 vs. baseline Scale ranges from 8 to 48 the higher score indicating worse symptoms. |
| Non- Motor Symptoms Scale (NMSS) | baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2) | Non-Motor Symptoms Scale (NMSS), which includes questions about 9 different categories of non-motor symptoms in PD, including urinary symptoms; Visit 3 and Visit 4 vs. baseline. Symptoms assessed over the last month. The scale ranges from 0 to 360, with higher scores indicating worse symptoms. |
| Patient Perception of Bladder Condition | baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2) | Patient Perception of Bladder Condition at Visit 3 and Visit 4 vs. baseline. the scale ranges from 1 to 6 with higher score indicating worse outcome |
| Subjects Global Impression of Change | baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2) | Subject's Global Impression of Change at Visit 3 and Visit 4 vs. baseline the scale ranges from 0 to 7 with higher score indicating worse out come . |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Daily OAB-SCS Visit 3 vs Baseline | baseline (7-14 days post visit 1) and visit 3 (32-40 days post visit 2) | The primary outcome measure will be the change in the mean daily Overactive Bladder-Symptom Composite Score (OAB-SCS) from baseline (visit 2) to visit 4. The Over active Bladder- Symptom Composite Score requires subjects to record the severity of urgency of each micturition over a 72 hour period. Subject ratings ranges from 1 to 6 for each micturition as follows: 1. Not at all, 2.A little bit, 3.Somewhat 4.Quite a bit, 5. A great deal, 6. A very great deal. Maximum score depends on number of micturition episodes in the 72 hour period, as the rating of each episode is summed to get the total score. Higher scores indicate worse symptoms of overactive bladder. |
| Change in Mean Number of Incontinence Episodes Per 24 Hours | baseline vs visit 3 (32-40 days post baseline) and baseline vs. visit 4 ((74-82 days post visit 2) | Subjects recorded in a 72-hour micturition diary the number of episodes of urinary incontinence, and this is averaged per 24 hours. Higher scores indicate more episodes of incontinence and thus worse outcome. |
Countries
United States
Participant flow
Pre-assignment details
Subjects who have met exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Mirabegron 1:1 randomization to receive Mirabegron 25 mg daily or placebo at visit 2. At visit 3 all subjects who have tolerated Mirabegron 25 md daily (no adverse events on this dose) will be up-titrated to Mirabegron 50 mg daily. This will be dispensed as two 25mg tablets or , for those in the placebo arm, two placebo tablets.
Mirabegron: 25 mg po daily for 32-40 days. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose.
Placebo: Placebo 25 mg po daily. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose. | 15 |
| Placebo 1:1 randomization to receive Mirabegron 25 mg daily or placebo at visit 2. At visit 3 all subjects who have tolerated Mirabegron 25 md daily (no adverse events on this dose) will be up-titrated to Mirabegron 50 mg daily. This will be dispensed as two 25mg tablets or , for those in the placebo arm, two placebo tablets.
Mirabegron: 25 mg po daily for 32-40 days. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose.
Placebo: Placebo 25 mg po daily. Following up-titration to 50 mg po daily. This is pending no adverse events on the 25 mg dose. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Placebo | Total | Mirabegron |
|---|---|---|---|
| Age, Customized Age,mean | 67 years | 67 years | 66 years |
| Race/Ethnicity, Customized Caucasian | 15 Participants | 30 Participants | 15 Participants |
| Region of Enrollment United States | 15 participants | 30 participants | 15 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Male | 10 Participants | 22 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 9 / 15 | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 | 1 / 15 |
Outcome results
Primary
Change in the Mean Daily Overactive Bladder-Symptom Composite Score.
The primary outcome measure will be the change in the mean daily Overactive Bladder-Symptom Composite Score (OAB-SCS) from baseline (visit 2) to visit 4. The Over active Bladder- Symptom Composite Score requires subjects to record the severity of urgency of each micturition over a 72 hour period. Subject ratings ranges from 1 to 6 for each micturition as follows: 1. Not at all, 2.A little bit, 3.Somewhat 4.Quite a bit, 5. A great deal, 6. A very great deal. Maximum score depends on number of micturition episodes in the 72 hour period, as the rating of each episode is summed to get the total score. Higher scores indicate worse symptoms of overactive bladder.
Time frame: 7-82 days. From visit 2 (baseline) to visit 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirabegron | Change in the Mean Daily Overactive Bladder-Symptom Composite Score. | -3.2 units on a scale | Standard Deviation 8.4 |
| Placebo | Change in the Mean Daily Overactive Bladder-Symptom Composite Score. | -8.9 units on a scale | Standard Deviation 7.9 |
Secondary
Non- Motor Symptoms Scale (NMSS)
Non-Motor Symptoms Scale (NMSS), which includes questions about 9 different categories of non-motor symptoms in PD, including urinary symptoms; Visit 3 and Visit 4 vs. baseline. Symptoms assessed over the last month. The scale ranges from 0 to 360, with higher scores indicating worse symptoms.
Time frame: baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron | Non- Motor Symptoms Scale (NMSS) | visit 3/baseline | -7.5 units on a scale | Standard Deviation 15.4 |
| Mirabegron | Non- Motor Symptoms Scale (NMSS) | visit 4/baseline | -10.5 units on a scale | Standard Deviation 18.5 |
| Placebo | Non- Motor Symptoms Scale (NMSS) | visit 3/baseline | -19.6 units on a scale | Standard Deviation 18.9 |
| Placebo | Non- Motor Symptoms Scale (NMSS) | visit 4/baseline | -17.9 units on a scale | Standard Deviation 23 |
Secondary
Overactive Bladder Questionnaire Symptom Severity Scale( OAB-q)
Overactive Bladder questionnaire symptom severity scale (OAB-q), Visit 3 and Visit 4 vs. baseline Scale ranges from 8 to 48 the higher score indicating worse symptoms.
Time frame: baseline (7-14 days post visit 1), visit 3( 32-40 days post visit 2) and visit 4(74-82 days post visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron | Overactive Bladder Questionnaire Symptom Severity Scale( OAB-q) | Week 3/baseline | -4.14 units on a scale | Standard Deviation 5.2 |
| Mirabegron | Overactive Bladder Questionnaire Symptom Severity Scale( OAB-q) | Week4/baseline | -2.6 units on a scale | Standard Deviation 7.9 |
| Placebo | Overactive Bladder Questionnaire Symptom Severity Scale( OAB-q) | Week 3/baseline | -3.2 units on a scale | Standard Deviation 4.8 |
| Placebo | Overactive Bladder Questionnaire Symptom Severity Scale( OAB-q) | Week4/baseline | -8.6 units on a scale | Standard Deviation 11.3 |
Secondary
Patient Perception of Bladder Condition
Patient Perception of Bladder Condition at Visit 3 and Visit 4 vs. baseline. the scale ranges from 1 to 6 with higher score indicating worse outcome
Time frame: baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron | Patient Perception of Bladder Condition | V3/baseline | -0.35 units on a scale | Standard Deviation 2.09 |
| Mirabegron | Patient Perception of Bladder Condition | V4/baseline | -0.38 units on a scale | Standard Deviation 1.9 |
| Placebo | Patient Perception of Bladder Condition | V3/baseline | -0.7 units on a scale | Standard Deviation 0.5 |
| Placebo | Patient Perception of Bladder Condition | V4/baseline | -1.2 units on a scale | Standard Deviation 2.18 |
Secondary
Subjects Global Impression of Change
Subject's Global Impression of Change at Visit 3 and Visit 4 vs. baseline the scale ranges from 0 to 7 with higher score indicating worse out come .
Time frame: baseline (7-14 days post visit 1), visit 3 (32-40 days post visit 2) and visit 4 (74-82 days post visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron | Subjects Global Impression of Change | visit 3/baseline | 3.5 units on a scale | Standard Deviation 1.8 |
| Mirabegron | Subjects Global Impression of Change | visit 4/baseline | 3.5 units on a scale | Standard Deviation 2.2 |
| Placebo | Subjects Global Impression of Change | visit 3/baseline | 3.0 units on a scale | Standard Deviation 1.3 |
| Placebo | Subjects Global Impression of Change | visit 4/baseline | 2.6 units on a scale | Standard Deviation 1.1 |
Other Pre-specified
Change in Mean Daily OAB-SCS Visit 3 vs Baseline
The primary outcome measure will be the change in the mean daily Overactive Bladder-Symptom Composite Score (OAB-SCS) from baseline (visit 2) to visit 4. The Over active Bladder- Symptom Composite Score requires subjects to record the severity of urgency of each micturition over a 72 hour period. Subject ratings ranges from 1 to 6 for each micturition as follows: 1. Not at all, 2.A little bit, 3.Somewhat 4.Quite a bit, 5. A great deal, 6. A very great deal. Maximum score depends on number of micturition episodes in the 72 hour period, as the rating of each episode is summed to get the total score. Higher scores indicate worse symptoms of overactive bladder.
Time frame: baseline (7-14 days post visit 1) and visit 3 (32-40 days post visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron | Change in Mean Daily OAB-SCS Visit 3 vs Baseline | visit 3 (32-40 days post visit 2 | 3.5 units on a scale | Standard Deviation 1.8 |
| Mirabegron | Change in Mean Daily OAB-SCS Visit 3 vs Baseline | baseline (7-14 days post visit 1) | 3.5 units on a scale | Standard Deviation 2.2 |
| Placebo | Change in Mean Daily OAB-SCS Visit 3 vs Baseline | visit 3 (32-40 days post visit 2 | 3.07 units on a scale | Standard Deviation 1.3 |
| Placebo | Change in Mean Daily OAB-SCS Visit 3 vs Baseline | baseline (7-14 days post visit 1) | 2.6 units on a scale | Standard Deviation 1.2 |
Other Pre-specified
Change in Mean Number of Incontinence Episodes Per 24 Hours
Subjects recorded in a 72-hour micturition diary the number of episodes of urinary incontinence, and this is averaged per 24 hours. Higher scores indicate more episodes of incontinence and thus worse outcome.
Time frame: baseline vs visit 3 (32-40 days post baseline) and baseline vs. visit 4 ((74-82 days post visit 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirabegron | Change in Mean Number of Incontinence Episodes Per 24 Hours | V3 vs baseline | -0.06 episodes per 24 hrs | Standard Deviation 0.82 |
| Mirabegron | Change in Mean Number of Incontinence Episodes Per 24 Hours | V4/baseline | 0.12 episodes per 24 hrs | Standard Deviation 1.24 |
| Placebo | Change in Mean Number of Incontinence Episodes Per 24 Hours | V3 vs baseline | -0.11 episodes per 24 hrs | Standard Deviation 1 |
| Placebo | Change in Mean Number of Incontinence Episodes Per 24 Hours | V4/baseline | -0.61 episodes per 24 hrs | Standard Deviation 1.9 |