Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intravesical Botulinum Toxin A Injection in Treatment of Interstitial Cystitis Refractory to Conventional Treatment - A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial
Brief Summary: This study was designed in a multicenter, randomized, double-blind, placebo controlled trial to test the actual therapeutic effects of intravesical BoNTA injection. The results of this study might provide clinical evidence for a better therapeutic regimen in the treatment of IC/PBS.


Options:
A: Inclusion Criteria:

* Patients with IC/PBS who have failed conventional treatments for at least 6 months will be enrolled.
* A diagnosis of IC/PBS has been established based on characteristic symptoms and cystoscopic findings of glomerulations, petechia, or mucosal fissures after hydrodistention.
* All patients have been treated with at least two types of treatment modalities including non-steroid anti-inflammatory drugs, oral pentosan polysulfate sodium (PPS), intravesical instillation of heparin, hyaluronic acid, or tricyclic antidepressant for at least 6 months but the symptoms remained unchanged or relapsed.

Exclusion Criteria:

* Exclusion criteria proposed by NIDDK
* Automatic exclusions:

  1. Age \<18 years old
  2. Benign or malignant bladder tumors
  3. Radiation cystitis Tuberculous cystitis
  4. Bacterial cystitis
  5. Vaginitis
  6. Cyclophosphamide cystitis
  7. Symptomatic urethral diverticulum
  8. Uterine, cervical, vaginal, or urethral cancer
  9. Active herpes
  10. Bladder or lower ureteral calculi
  11. Waking frequency \<5 times in 12 hours
  12. Nocturia \<2 times
  13. Symptoms relieved by antibiotics, urinary antiseptics, urinary analgesics (for example phenazopyridine hydrochloride)
  14. Duration \< 12 months
  15. Involuntary bladder contractions (urodynamics)
  16. Capacity \> 400ml, absence of sensory urgency
* Automatic inclusions:

  1.Hunner's ulcer
* Positive factors: (two positive factors are necessary for inclusion)

  1. Pain on bladder filling relieved by emptying
  2. Pain (suprapubic, pelvic, urethral, vaginal or peripheral)
  3. Glomerulations on endoscopy
  4. Decreased compliance on cystometrogram
  5. Bladder distention is defined arbitrarily as 80 cm water pressure for 1 minute
* Use of Anticholinergic drugs, for the treatment of lower urinary tract symptoms who have an effect.
* Patients with severe cardiopulmonary disease and such as congestive heart failure, arrhythmia, poorly controlled hypertension, not able to receive regular follow-up.
* Patients with bladder outlet obstruction on enrollment.
* Patients with urinary retention, PVR≥150 ml.
* Patients with uncontrolled confirmed diagnosis of acute urinary tract infection.
* Patients have laboratory abnormalities at screening including:

  1. Alanine aminotransferase (ALT) \> 3 x upper limit of normal range
  2. Aspartate aminotransferase (AST) \> 3 x upper limit of normal range.
  3. Patients have abnormal serum creatinine level \> 2 x upper limit of normal range.
* Can not be used in the treatment of patients with transurethral catheter treatment.
* Pregnant and lactating women or women who intend to become pregnant during the study or have myasthenia gravis, Eaton Lambert syndrome.
* Patients with any other serious disease or condition considered by the investigator not suitable for entry into the trial.
* Patients participated investigational drug trial within 1 month before entering this study.
* Written informed consent has been obtained.
* Patient who did not complete the 3-day micturition diary according to the instruction.
* Intestinal bladder augmentation patients receive angioplasty for the treatment of overactive bladder.
B: Inclusion Criteria:

* Chronic pelvic pain (\>6 months) perceived to be related to the urinary bladder and accompanied by urinary symptoms such as frequent urination during the day and/or night, and/or urgency to void
* Total score of 8 or greater on the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI)
* The mean of the average pain intensity scores at screening phase \>=5 (on a scale of 0 to 10)
* Medically stable

Exclusion Criteria:

* Urinary culture is positive for a urinary tract infection; Recent invasive therapy to the bladder
* History or current conditions indicating that the bladder pain can be caused by diagnoses other than IC/PBS (eg, pain caused by a confirmed or suspected neoplasm)
* History of malignancy within the past 2 years, with the exception of basal cell carcinoma that has been successfully treated
* Women who are pregnant or breast-feeding
* A body mass index (BMI) of \>39 kg/m2
C: 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
D: Inclusion Criteria:

* Males or females ≥18 and ≤ 65 years of age previously diagnosed with Interstitial Cystitis
* Currently have symptoms of urinary urgency, frequency or pain for more than 6 months
* Urinating at least 7 times a day or having some urgency or pain (measured on linear analog scales)
* Must be post-menopausal or surgically sterile or willing to use an adequate form of birth control
* Not pregnant or lactating
* Capable of voiding independently
* Willing to provide informed consent to participate

Exclusion Criteria:

* Have symptoms that are presently relieved on other medications for interstitial cystitis
* Have absence of nocturia
* Have symptoms that are relieved by antimicrobials or antibiotics.
* Have a body mass index (BMI) of \>39 kg/m2
* Have uncontrolled hypertension
* Have Type I or type 2 diabetes
* Have active Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) infection, or who are known carriers (Hepatitis B) at Screening
* Have a positive tuberculosis test at screening
* Have had a urinary tract infection for 6 weeks
* Have had bacterial cystitis in previous 3 months
* Have had previous exposure to Humira® (adalimumab)
* Have taken investigational medication within 30 days of screening
* Have any other condition/disease which, in the opinion of the investigator, could compromise subject safety or confound the interpretation of study results
* Are unable or unwilling to comply with protocol requirements

Answer: A