A Pilot Study of the Effects of Mirabegron on Symptoms in Patients With Interstitial Cystitis
Condition: Cystitis, Interstitial
MeSH terms: Cystitis; Cystitis, Interstitial
Intervention: Mirabegron; Placebo
Intervention MeSH terms: Mirabegron
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 9.0
Sex: Female
Minimum age: 18 Years
Maximum age: 95 Years
Healthy volunteers: No
Keywords: Interstitial Cystitis

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