Clinical trial NCT02044510 (phase 2/phase 3, status: terminated)
Conditions: urinary bladder, neurogenic
ICD codes: G98.0, K59.2, M48.061, M48.062
Drugs: mirabegron, placebo
SMILES: NC1=NC(CC(=O)NC2=CC=C(CCNC[C@H](O)C3=CC=CC=C3)C=C2)=CS1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    slow recruitment and small observed effect size
  
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.