Cystitis, Interstitial
Conditions
Keywords
Interstitial Cystitis
Brief summary
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a difficult disease to both diagnose and treat. It is defined as an unpleasant sensation (pain, pressure, or discomfort) perceived to be related to the urinary bladder and associated with lower urinary tract symptoms for at least 6 weeks duration, in the absence of infection or other identifiable causes. Pain is the universal symptom, but many also experience symptoms of overactive bladder, possibly directly related to the mechanism of pain. Treating pain may influence the symptom of urgency, if the urge arises from a need to alleviate pain. In some patients whose pain improves with treatment, troubling overactive bladder symptoms still remain. Beta-3 adrenergic agonists have been found to decrease signaling of C-fibers in animal models. So, the investigators hypothesize that mirabegron, which is FDA-approved for treatment of overactive bladder, would also improve symptoms in patients with BPS/IC. As a selective beta-3 agonist, mirabegron acts on the beta-3 receptors found in the bladder which mediate relaxation of the detrusor muscle. It has been shown to significantly decrease the number or micturition episodes, urgency episodes, and increased mean volume of urine voided per micturition. It also has a favorable tolerability profile.
Interventions
DRUGMirabegron
DRUGPlacebo
Sponsors
Astellas Pharma Global Development, Inc.
Philadelphia Urosurgical Associates
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
1. Participants must be diagnosed with BPS/IC with a minimum O'Leary-Sant score of 8 on the ICSI, as well as 8 on the ICPI. Participants should be stable on their regimen (no increase or change in medications, behavioral treatments or physical therapy in previous 4 weeks prior to starting the study) and be willing to remain on this regimen during the duration of the study. 1. Participant must be stable on current IC/BPS regimen. 2. Participant must have subjective complaints of i. urinary urgency, relieved with voiding or ii. urinary frequency; ≥ 8 voids per day iii. pelvic pain, pressure, hypersensitivity or discomfort 2. Gender of subjects: Participants in this study will be female. Pregnant women and breastfeeding women will be excluded due to unknown risk of study medication on pregnancy and fetus or nursing infants. 3. Age of subjects: Age of participants will range from 18 to 95 years. 4. Racial and ethnic origin: There are no enrollment restrictions based upon race or ethnic origin. The racial and ethnic distribution of participants is entirely based on the population of patients at the study site. 5. Other inclusion criteria: 1. Participant must give written informed consent to participate in the study 2. Participant must be able to make decisions for herself 3. Participant must have a negative urine dip within 7 days prior to start of the study 4. Female participants who are of childbearing age and sexually active with men must agree to use a medically acceptable method of contraception throughout the study period, and for 7 days after the study period. Medically acceptable methods of contraception include abstinence, oral contraceptive pills, hormonal contraceptive patches, diaphragm with or without spermicide, IUD, condoms, depot medroxyprogesterone acetate, subdermal progestin implants, vasectomized partner, or status post surgical sterilization.
Exclusion criteria
To participate in the study subjects must not meet any of the following criteria: 1. Participant is currently pregnant or breastfeeding 2. Participant has a positive urinary pregnancy test at the time of screening 3. Participant is currently or has been on antibiotic therapy with the last 7 days prior to the start of the study 4. Participant is an employee of Astellas, or any other pharmaceutical company or the Pelvic and Sexual Health Institute 5. Participant is currently in another pharmaceutical trial 6. Participant has used anticholinergic medications, tamsulosin or opioid narcarotic medication within the last 30 days prior to the study or during the study period. Participants will be able to use rescue medications for BPS/IC symptom flares including non-opioid narcotics, non-steroidal anti-inflammatory agents, pyridium and uribel. 7. Participant has had bladder hydrodistention or bladder instillations within the last 4 weeks. Participants may have bladder instillations during the study period if necessary for rescue from symptom flares. 8. Participant has used or currently using CYP2D6 substrates, such as thioridazine, flecainide, propafenone, within the last 7 days prior to the study or during study period 9. Participant has used warfarin or digoxin within the last 7 days prior to the study or during the study period 10. Participant has used cyclosporine within the 7 days prior to the study or during the study period 11. Participant has an active S3 nerve stimulator implanted or has had PTNS within 6 months prior to starting the study 12. Participant has not had intravesical botulinum toxin injection in 6 months prior to starting the study 13. Participant has grade III or IV pelvic organ prolapse 14. Participant has been diagnosed with a urinary tract infection within the last 4 weeks prior to starting the study 15. Participant has history of bladder cancer 16. Participant is currently an alcohol or substance abuser, or is a chronic opioid user 17. Participant has history of renal failure (GFR \<30) or liver failure (CHILD score B or C) 18. Participant has urinary retention defined as greater than 150cc post-void residual as diagnosed by catheterization, bladder ultrasound scan or urodynamic testing within the last 14 days. 19. Participant has history of severe uncontrolled blood pressure (defines as systolic greater than or equal to 180mm Hg and/or diastolic blood pressure greater than or equal to 110 mm Hg) 20. Participant has a neurological disease including, but not limited to, multiple sclerosis, Parkinson's disease, Alzheimer's disease, spinal cord injury, brain injury, stroke or dementia 21. Participant has urinary frequency of less than 8 times/day 22. Participant has bladder or lower ureteral calculi 23. Participant has active genital herpes 24. Participant has urethral diverticulum 25. Participant has chemical cystitis 26. Participant has radiation or tuberculosis cystitis 27. Participant has known hypersensitivity to mirabegron or any of the inactive ingredients in the supplied form of mirabegron
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Interstitial Cystitis Symptom Improvement | 12 weeks | Evaluate urinary urgency, frequency and pain via validated O'Leary Sant questionnaire |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement in Incontinence Episodes | 12 weeks | Evaluate incontinence episodes via bladder diary and UDI-6 questionnaire |
| Impact on Quality of Life | 12 weeks | Evaluate impact on quality of life from bladder, bowel and vaginal/pelvic symptoms via PFIQ-7 questionnaire |
| Patient Satisfaction | 12 weeks | evaluate participant satisfaction with treatment/placebo via Global response assessment form |
| Sexual Function | 12 weeks | Evaluate changes in sexual function via FSFI questionnaire |
| Side Effects of Medication | 12 weeks | Will assess if participants have side effects of medication via office visits |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mirabegron These patients will receive mirabegron 50mg tablets daily for 12 weeks.
Mirabegron | 4 |
| Placebo These patients will receive placebo tablets daily for 12 weeks.
Placebo | 5 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Mirabegron | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 9 Participants |
| Region of Enrollment United States | 4 participants | 5 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Systolic | 145 MMHg | 145 MMHg | 145 MMHg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 1 / 4 | 0 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 |
Outcome results
Primary
Number of Participants With Interstitial Cystitis Symptom Improvement
Evaluate urinary urgency, frequency and pain via validated O'Leary Sant questionnaire
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirabegron | Number of Participants With Interstitial Cystitis Symptom Improvement | 1 Participants |
| Placebo | Number of Participants With Interstitial Cystitis Symptom Improvement | 3 Participants |
Secondary
Impact on Quality of Life
Evaluate impact on quality of life from bladder, bowel and vaginal/pelvic symptoms via PFIQ-7 questionnaire
Time frame: 12 weeks
Secondary
Number of Participants With Improvement in Incontinence Episodes
Evaluate incontinence episodes via bladder diary and UDI-6 questionnaire
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mirabegron | Number of Participants With Improvement in Incontinence Episodes | 1 Participants |
| Placebo | Number of Participants With Improvement in Incontinence Episodes | 3 Participants |
Secondary
Patient Satisfaction
evaluate participant satisfaction with treatment/placebo via Global response assessment form
Time frame: 12 weeks
Secondary
Sexual Function
Evaluate changes in sexual function via FSFI questionnaire
Time frame: 12 weeks
Secondary
Side Effects of Medication
Will assess if participants have side effects of medication via office visits
Time frame: 12 weeks