Intervention: Mirabegron
Trial phase: Phase 2 | Phase 3
ATC code: G04BD12
SMILES: Nc1nc(CC(=O)Nc2ccc(CCNC[C@H](O)c3ccccc3)cc2)cs1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 32
Group description: Patients randomised to this arm start with mirabegron 25mg PO daily for two weeks, and then at 2 weeks titrate to 50mg PO daily, and maintain that dose for the duration of the study (8 additional weeks).

Mirabegron: Mirabegron 25mg PO daily for 2 weeks, with dose increase to Mirabegron 50mg PO daily for the remaining 8 weeks.
Eligibility criteria:
Inclusion criteria:

Diagnosis of traumatic or nontraumatic suprasacral spinal cord injury (SCI) or multiple sclerosis (MS, based on a neurologist assessment and/or the McDonald criteria)(28)
Age >18 years
Stable method of bladder management for >3months (either spontaneous or provoked voiding, or intermittent catheterization).
Bothersome urinary symptoms (urinary frequency, urgency, or urgency incontinence based on standard ICS definitions(29)) and completed 3 day voiding diary demonstrating at least 1 episode of non-stress based urinary incontinence over the 72hr period (this may be urgency based incontinence or unaware incontinence).
Patient is able to read and speak English

Exclusion criteria:

Based on Screening visit history:

Participation in another drug or device study in the 60 days prior to the screening visit.
Previous urologic surgery: Transurethral prostatectomy, bladder augmentation, sphincterotomy, bladder neck sling, artificial urinary sphincter, catheterizable channel, implantable electrostimulator/neuromodulator
Current use of suprapubic catheter/foley catheter
Unstable cardiac disease (uncontrolled hypertension, myocardial infarction, unstable angina, severe congestive heart failure (NYHA 3 or 4), ventricular arrhythmia (such as torsades de pointes), or stroke within the last 6 months)
Clinically significant abnormal ECG
The investigator believes the patient has an increased risk of QT prolongation (based on review of the screening ECG and patients concurrent medications)
History of significant renal dysfunction within 1 year, or serum creatinine >150umol/L at screening visit (visit 1).
History of significant liver disease within 1 year, or serum AST/ALT >2 times upper limit of normal, GGT >3 times upper limit of normal, total bilirubin >2 times upper limit of normal at screening visit (visit 1).
History of pelvic radiation
History of bladder cancer
History of a concurrent malignancy or cancer (except noninvasive skin cancer) within the last 5 years. Subjects with a history of cancer are considered eligible if the subject has undergone potentially curative therapy and the subject has been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin).
Patient has a history of interstitial cystitis/pelvic pain syndrome
Patient has a history of acute or chronic urinary retention within the last 3 months, and is currently not using intermittent catheters
Patient has a history of a tachyarrhythmia
Patient has a history of glaucoma
Patient has a medical condition that may cause noncompliance with the study protocol
In the opinion of the Investigator the patient has a history of significant stress urinary incontinence

Patient has signs and symptoms of an active urinary tract infection (symptoms of dysuria, foul smelling urine, cloudy urine, increased spasticity, increased autonomic dysreflexia, self reported fever, increased incontinence, back/suprapubic pain).

o Patient will submit urine for culture and sensitivity, undergo treatment, and will be eligible for rescreening after treatment.

Female patient who is pregnant or breastfeeding, or plans to become pregnant.
Male patient who is planning on fathering a child during the study or for 28 days after the last dose of study drug, or who is planning to donate sperm
Patient refuses to provide written consent
Patient will be unable or unwilling to complete the questionnaires and study visits
In the opinion of the study investigator, it is not in the patient's best interest to be enrolled in this study.

Based on medication and allergy review

The new addition of an anticholinergic medication, or a change to anticholinergic dose, within the last 30 days, (bladder specific anticholinergics include oxybutynin, tolterodine, fesoterodine, solifenacin, darifenacin, trospium, hyoscine, oxybutynin gel or patch, atropine, benzatropine). If previously used and discontinued, these medications must have been stopped for >2 weeks
Newly added bladder active medication (or dose change) within the last 2 months (Tamsulosin, Silodosin, Terazosin, Baclofen, Diazepam, amitriptyline, Finasteride, Dutasteride, DDAVP/desmopressin)
Use of flecainide, propafenone, donepezil, thioridazine, tramadol, aripiprazole, desipramine, imipramine, venlafaxine or digoxin
Intravesical onabotulinum toxin use within the last 1 year
Intravesical oxybutynin within the last 3 months
Patient has a previous history of treatment with mirabegron
Patient has a known allergy to mirabegron or a previous adverse reaction to a beta 3 agonist.

Based on physical exam

Patient has a postvoid residual > 250mL at study enrollment after repeated tested (1 attempt to re-void to ensure complete emptying of the bladder) and is not using intermittent catheters
Patient has a resting BP >180 mmHg systolic and/or >110 mmHg diastolic after 2 minutes of sitting quietly
Patient has a resting heart rate >100bpm after 2 minutes of sitting quietly
In the opinion of the study investigator, it is not in the patient's best interest to be enrolled in this study based on a clinically significant abnormality on physical exam.