Overactive Bladder in Parkinson's Disease
Conditions
Keywords
Overactive bladder, Urinary incontinence, Urinary frequency, Parkinson's disease
Brief summary
This study will assess the effectiveness of solifenacin succinate (VESIcare) in reducing symptoms of overactive bladder in Parkinson's disease (PD) patients.
Interventions
up to 10mg every day orally
DRUGplacebo
placebo matching solifenacin succinate (VESIcare) up to 10mg orally every day
Sponsors
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Outpatients with idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria. 2. Age 40 years to 80 years. 3. Stable dose of antiparkinsonian medication 4 weeks prior to study entry. 4. Patients must score 1.0 to 3.0 on the Modified Hoehn and Yahr scale. 5. Women of child-bearing potential must use a reliable method of contraception. 6. Must be experiencing symptoms of overactive bladder according to the ICS definition of a minimum voiding 8 or more times/24 hours and a daily average of at least 1 episode of urgency and/or urinary incontinence (urge incontinence predominately as measured by 3IQ diary) per 24 hours during a 3-day micturition diary period. Patients must have documentation of OAB within the last 6 months. 7. The patient must have evidence of PSA less than or equal to 4 (males only) within the last 12 months (obtained from primary care physician). 8. The patient must have had a bladder scan within six months of the screening visit. This scan uses ultrasound technology to measure residual fluid levels in the bladder after urination. This scan must document post void residual of 200 mls or less. A bladder scan printout or a note documenting these findings must be provided before baseline. 9. Clearance from the patient's internist or primary care health provider who has examined the patient within the last 6 months.
Exclusion criteria
1. Any illness that in the investigator's opinion preclude participation in this study. 2. Pregnancy or lactation. 3. Concurrent participation in another clinical study. 4. Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini Mental Status Exam scores less than 27). 5. Legal incapacity or limited legal capacity. 6. History of prostate cancer or Transurethral resection of the prostate (TURP) (males only). 7. Presence of severe renal disease. BUN 50% greater than normal (normal BUN levels should be within a range of 5 to 20 mg/ d L and creatinine between .7 and 1.4 mg/ d L). Labs within the past 12 months will be requested from the patient's health care provider or urologist. If labs are not available within this time-frame or if results are abnormal, labs will be obtained as part of the screening visit. 8. Presence of major hepatic impairment (cirrhosis, viral hepatitis, nonalcoholic steatohepatitis, Wilson's disease, or Hemochromotosis). 9. Currently taking ketaconazole (anti-fungal) or any CYP3A4 inhibitor such as itraconazole, ritonavir, nelfinavir, clarithromycin, or nefazadone. 10. Any history of bladder outflow obstruction or gastrointestinal obstructive disorders. 11. History of narrow angle glaucoma. 12. Patients who have undergone pelvic radiation at any time. 13. Currently taking any of the following medications: * Antiarrhythmics: flecainide (Almarytm, Apocard, Ecrinal, Flécaine), digoxin (Lanoxin, Digitek, Lanoxicaps) * Antipsychotics: thioridazine (Mellaril, Novorizadine, Thioril) * Tricyclic anti-depressants: amitriptyline (Elavil, Tryptanol, Endep, Elatrol, Tryptizol, Trepiline, Laroxyl), amoxapine (Asendin, Asendis, Defanyl, Demolox, Moxadil), clomipramine (Anafranil), desipramine (Norpramin, Pertofrane), imipramine (Antideprin, Deprenil, Deprimin, Deprinol, Depsonil, Dynaprin, Eupramin, Imipramil, Irmin, Janimine, Melipramin, Surplix, Tofranil), nortriptyline (Aventyl, Pamelor, Nortrilen), protriptyline (Vivactil), trimipramine (Stangyl, Surmontil, Rhotrimine) * Psychotropics: doxepin (Aponal, Adapine, Sinquan, Sinequan) * Anticholinergics/Antispasmodics: trihexyphenidyl (Artane, Aparkan), benztropine (Cogentin), oxybutynin (Ditropan, Ditropan XL, Lyrinel XL, Oxytrol), darifenacin (Enablex), emepronium, flavoxate (Urispas), meladrazine, propiverine, solifenacin (Vesicare), tolterodine (Detrol, Detrol LA), trospium (Sanctura) * Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRI): duloxetine (Cymbalta, Yentreve), Venlafaxine (Effexor, Effexor XR) * Arylalkylamines: pseudoephedrine (Sudafed) * Anti-androgen: bicalutamide (Casodex, Cosudex, Calutide, Kalumid), finasteride (Proscar, Propecia, Fincar, Finpecia, Finax, Finast, Finara, Finalo, Prosteride, Gefina, Finasterid IVAX), dutasteride (Avodart, Avidart, Avolve, Duagen, Dutas, Dutagen, Duprost), Zoladex (goserelin acetate), Eulexin (flutamide), Lupron (leuprolide acetate) * Antihypertensives: prazosin (Minipress, Vasoflex, Hypovase) * Estrogens (Menest, Premarin, Premarin IV) * Acetylcholinesterase inhibitors (rivastigmine (Exelon), galantamine, (Reminyl, donepezil (Aricept), Tacrine. * Memantine (Namenda) 14. Urinary obstruction in male PD patients as diagnosed by a urologist 15. Active urinary tract infection. 16. Patients with a history of chronic severe constipation (by self report)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Micturations Per 24 Hour Period | 12 weeks | The primary objective of this study is to measure the efficacy of solifenacin succinate (VESIcare) in reducing the mean number of micturitions per 24 hour period in Parkinson's disease (PD) patients as measured by voiding diaries. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Urinary Incontinence Episodes Per 24 Hour Period | 12 weeks | This scale it the mean number of urinary incontinence episodes per 24 hour period, as assessed by a 3-day bladder diary. The goal is to examine the effect of solifenacin succinate (VESIcare) on urinary incontinence severity. |
| Unified Parkinson's Disease Rating Scale (UPDRS) Total | 12 weeks | To examine the effect of solifenacin succinate (VESIcare) on Parkinson's disease severity. The UPDRS total score ranges from 0 (no disability) to 199 (total disability). |
| Parkinson's Disease Quality of Life Scale (PDQOL) | 12 weeks | This scale is used to assess quality of life in Parkinson's Disease patients. Parkinson's disease quality of life scale has a possible point range from 37 (worst outcome) to 185 (best outcome). The goal of this outcome measure is to examine the effect of solifenacin succinate (VESIcare) on quality of life. |
| Number of Nocturia Episodes Per 24 Hour Period | 12 weeks | To examine the effect of solifenacin succinate (VESIcare) on urinary incontinence severity |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Solifenacin Succinate (VESIcare) solifenacin succinate (VESIcare): up to 10mg every day orally | 10 |
| Placebo placebo: placebo matching solifenacin succinate (VESIcare) up to 10mg orally every day | 13 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Solifenacin Succinate (VESIcare) |
|---|---|---|---|
| Age, Customized Age (years) | 66.5 years STANDARD_DEVIATION 9.3 | 66.96 years STANDARD_DEVIATION 8.04 | 67.6 years STANDARD_DEVIATION 6.6 |
| Bladder diary: # leaks | 1.72 Number of leaks per 24-hour period STANDARD_DEVIATION 1.23 | 1.55 Number of leaks per 24-hour period STANDARD_DEVIATION 1.82 | 1.33 Number of leaks per 24-hour period STANDARD_DEVIATION 2.45 |
| Bladder diary: # micturations | 9.23 Micturation episodes per 24 hour period STANDARD_DEVIATION 3.31 | 9.14 Micturation episodes per 24 hour period STANDARD_DEVIATION 2.83 | 9.03 Micturation episodes per 24 hour period STANDARD_DEVIATION 2.21 |
| Bladder diary: # nocturia episodes | 1.90 Number of nocturia episodes per 24 hours STANDARD_DEVIATION 1.09 | 2.04 Number of nocturia episodes per 24 hours STANDARD_DEVIATION 1.36 | 2.23 Number of nocturia episodes per 24 hours STANDARD_DEVIATION 1.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 21 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hoehn & Yahr stage Stage 1 | 0 participants | 1 participants | 1 participants |
| Hoehn & Yahr stage Stage 1.5 | 1 participants | 2 participants | 1 participants |
| Hoehn & Yahr stage Stage 2 | 2 participants | 3 participants | 1 participants |
| Hoehn & Yahr stage Stage 2.5 | 7 participants | 13 participants | 6 participants |
| Hoehn & Yahr stage Stage 3 | 3 participants | 4 participants | 1 participants |
| Incontinence Quality of Life scale (IQOL) | 75.92 units on a scale STANDARD_DEVIATION 18.87 | 76.83 units on a scale STANDARD_DEVIATION 18.96 | 78.00 units on a scale STANDARD_DEVIATION 20.03 |
| Parkinson's Disease Quality of Life (PDQOL) total score | 115.31 units on a scale STANDARD_DEVIATION 10.68 | 119.13 units on a scale STANDARD_DEVIATION 15.65 | 124.10 units on a scale STANDARD_DEVIATION 19.96 |
| Patient perception of Bladder Condition (PBC/PPBC) Causes me many severe problems | 1 participants | 2 participants | 1 participants |
| Patient perception of Bladder Condition (PBC/PPBC) Causes me severe problems | 7 participants | 11 participants | 4 participants |
| Patient perception of Bladder Condition (PBC/PPBC) Causes me (some) moderate problems | 5 participants | 10 participants | 5 participants |
| Patient Perception of Intensity of Urgency Scale (PPIUS) Mild Urgency | 1 participants | 4 participants | 3 participants |
| Patient Perception of Intensity of Urgency Scale (PPIUS) Moderate-Severe | 1 participants | 1 participants | 0 participants |
| Patient Perception of Intensity of Urgency Scale (PPIUS) Moderate Urgency | 5 participants | 9 participants | 4 participants |
| Patient Perception of Intensity of Urgency Scale (PPIUS) Severe Urgency | 6 participants | 9 participants | 3 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 18 Participants | 8 Participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 15 Participants | 7 Participants |
| Unified Parkinson's Disease Rating Scale (UPDRS) ADL subsection (mean) | 11.23 units on a scale STANDARD_DEVIATION 4.76 | 10.48 units on a scale STANDARD_DEVIATION 5.01 | 9.50 units on a scale STANDARD_DEVIATION 5.4 |
| Unified Parkinson's Disease Rating Scale (UPDRS) Motor subsection (Part III) | 14.69 points STANDARD_DEVIATION 5.19 | 13.78 points STANDARD_DEVIATION 4.86 | 12.60 points STANDARD_DEVIATION 4.38 |
| Unified Parkinson's Disease Rating Scale (UPDRS) Total score | 25.08 units on a scale STANDARD_DEVIATION 11.93 | 24.61 units on a scale STANDARD_DEVIATION 10.78 | 24.00 units on a scale STANDARD_DEVIATION 9.67 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 10 | 0 / 13 |
| serious Total, serious adverse events | 0 / 10 | 0 / 13 |
Outcome results
Primary
Number of Micturations Per 24 Hour Period
The primary objective of this study is to measure the efficacy of solifenacin succinate (VESIcare) in reducing the mean number of micturitions per 24 hour period in Parkinson's disease (PD) patients as measured by voiding diaries.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate (VESIcare) | Number of Micturations Per 24 Hour Period | Endpoint (12 weeks) | 8.00 Number of micturations per 24 hours | Standard Deviation 3.36 |
| Solifenacin Succinate (VESIcare) | Number of Micturations Per 24 Hour Period | Baseline | 8.78 Number of micturations per 24 hours | Standard Deviation 2.18 |
| Placebo | Number of Micturations Per 24 Hour Period | Baseline | 9.19 Number of micturations per 24 hours | Standard Deviation 3.46 |
| Placebo | Number of Micturations Per 24 Hour Period | Endpoint (12 weeks) | 8.94 Number of micturations per 24 hours | Standard Deviation 3.06 |
p-value: 0.53ANCOVA
Secondary
Number of Nocturia Episodes Per 24 Hour Period
To examine the effect of solifenacin succinate (VESIcare) on urinary incontinence severity
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate (VESIcare) | Number of Nocturia Episodes Per 24 Hour Period | Baseline | 2.48 Number of nocturia episodes per 24 hours | Standard Deviation 1.59 |
| Solifenacin Succinate (VESIcare) | Number of Nocturia Episodes Per 24 Hour Period | Endpoint (12 weeks) | 2.04 Number of nocturia episodes per 24 hours | Standard Deviation 1.96 |
| Placebo | Number of Nocturia Episodes Per 24 Hour Period | Baseline | 1.92 Number of nocturia episodes per 24 hours | Standard Deviation 1.14 |
| Placebo | Number of Nocturia Episodes Per 24 Hour Period | Endpoint (12 weeks) | 1.78 Number of nocturia episodes per 24 hours | Standard Deviation 0.88 |
p-value: 0.94ANCOVA
Secondary
Number of Urinary Incontinence Episodes Per 24 Hour Period
This scale it the mean number of urinary incontinence episodes per 24 hour period, as assessed by a 3-day bladder diary. The goal is to examine the effect of solifenacin succinate (VESIcare) on urinary incontinence severity.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate (VESIcare) | Number of Urinary Incontinence Episodes Per 24 Hour Period | Baseline | 1.48 Number of incontinence episodes/24 hours | Standard Deviation 2.56 |
| Solifenacin Succinate (VESIcare) | Number of Urinary Incontinence Episodes Per 24 Hour Period | Endpoint (12 weeks) | 0.30 Number of incontinence episodes/24 hours | Standard Deviation 0.31 |
| Placebo | Number of Urinary Incontinence Episodes Per 24 Hour Period | Baseline | 1.78 Number of incontinence episodes/24 hours | Standard Deviation 1.27 |
| Placebo | Number of Urinary Incontinence Episodes Per 24 Hour Period | Endpoint (12 weeks) | 1.61 Number of incontinence episodes/24 hours | Standard Deviation 1.4 |
p-value: 0.01ANCOVA
Secondary
Parkinson's Disease Quality of Life Scale (PDQOL)
This scale is used to assess quality of life in Parkinson's Disease patients. Parkinson's disease quality of life scale has a possible point range from 37 (worst outcome) to 185 (best outcome). The goal of this outcome measure is to examine the effect of solifenacin succinate (VESIcare) on quality of life.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate (VESIcare) | Parkinson's Disease Quality of Life Scale (PDQOL) | Baseline | 125.00 units on a scale | Standard Deviation 20.95 |
| Solifenacin Succinate (VESIcare) | Parkinson's Disease Quality of Life Scale (PDQOL) | Endpoint (12 weeks) | 116.00 units on a scale | Standard Deviation 26.42 |
| Placebo | Parkinson's Disease Quality of Life Scale (PDQOL) | Baseline | 114.50 units on a scale | Standard Deviation 10.73 |
| Placebo | Parkinson's Disease Quality of Life Scale (PDQOL) | Endpoint (12 weeks) | 112.92 units on a scale | Standard Deviation 17.19 |
p-value: 0.47ANCOVA
Secondary
Unified Parkinson's Disease Rating Scale (UPDRS) Total
To examine the effect of solifenacin succinate (VESIcare) on Parkinson's disease severity. The UPDRS total score ranges from 0 (no disability) to 199 (total disability).
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Solifenacin Succinate (VESIcare) | Unified Parkinson's Disease Rating Scale (UPDRS) Total | Baseline | 25.00 units on a scale | Standard Deviation 9.7 |
| Solifenacin Succinate (VESIcare) | Unified Parkinson's Disease Rating Scale (UPDRS) Total | Endpoint (12 weeks) | 21.67 units on a scale | Standard Deviation 9.59 |
| Placebo | Unified Parkinson's Disease Rating Scale (UPDRS) Total | Baseline | 25.67 units on a scale | Standard Deviation 12.26 |
| Placebo | Unified Parkinson's Disease Rating Scale (UPDRS) Total | Endpoint (12 weeks) | 25.75 units on a scale | Standard Deviation 8.76 |
p-value: 0.22ANCOVA