Clinical trial NCT02787083: A Pilot Study of the Effects of Mirabegron on Symptoms in Patients With Interstitial Cystitis
Official title: A Pilot Study of the Effects of Mirabegron on Symptoms in Patients With Interstitial Cystitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cystitis, Interstitial
Keywords: Interstitial Cystitis
Lead sponsor: Philadelphia Urosurgical Associates
Sponsor class: OTHER
Collaborators: name: Astellas Pharma Global Development, Inc.
First posted: 2016-06-01
Enrollment: 9
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Interstitial Cystitis Symptom Improvement
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of Participants With Improvement in Incontinence Episodes
timeFrame: 12 weeks
measure: Impact on Quality of Life
timeFrame: 12 weeks
measure: Patient Satisfaction
timeFrame: 12 weeks
measure: Sexual Function
timeFrame: 12 weeks
measure: Side Effects of Medication
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Philadelphia Urosurgical Associates
state: Pennsylvania
Study officials:
affiliation: Philadelphia Urosurgical Associates
name: Kristene E Whitmore, MD
role: STUDY_DIRECTOR
References:
citation: Imamura M, Scott NW, Wallace SA, Ogah JA, Ford AA, Dubos YA, Brazzelli M. Interventions for treating people with symptoms of bladder pain syndrome: a network meta-analysis. Cochrane Database Syst Rev. 2020 Jul 30;7(7):CD013325. doi: 10.1002/14651858.CD013325.pub2.