Add-on Mirabegron in Pediatric Patients With Refractory Overactive Bladder
Condition: Overactive Bladder; Urinary Incontinence
MeSH terms: Urinary Incontinence; Urinary Bladder, Overactive
Intervention: Mirabegron
Intervention description: Patients will keep the antimuscarinic providing some efficacy and that is tolerated and Mirabegron will be added (dual therapy).
Intervention MeSH terms: Mirabegron
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 5 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: mirabegron; antimuscarinics; beta 3 agonist; overactive bladder; children

Summary:

      The objective is to evaluate the efficacy and safety of adding mirabegron to an
      antimuscarinic to treat urinary incontinence in children with Overactive Bladder that are
      refractory to antimuscarinics.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female ≥ 5 years old and ≤17 years old

          -  OAB diagnostic according to the International Children Continence Society (ICCS) and
             less than 65% of the expected mean bladder capacity for age is confirmed (30 + (age in
             years x 30) mL) on a 3-day voiding diary.

          -  Weight and height are within the normal percentile (3rd to 97th percentile) and weight
             is ≥ 20 kg (3rd percentile of a 8 y.o. child, boy or girl), according to the CDC
             growth chart

          -  Ability to swallow pills

          -  Subjects/parents (vs. legal guardian) agree to participate to the following study and
             sign the informed consent

          -  Subjects/parents (vs. legal guardian) are able to comply with the study requirements
             and with the medication restrictions.

          -  Female subjects of childbearing potential must have a negative serum or urine
             pregnancy test at enrollment and must agree to maintain highly effective birth control
             during the study. Sexually active male subjects agree to use a barrier method of birth
             control with female partner for the duration of the study and at least one month after
             ending study treatment. Sexually active male subjects agree to use a condom for the
             duration of the study and for at least one month after ending study treatment and the
             female partner to use a reliable form of birth control for the duration of the study
             and for at least one month after ending study treatment.

          -  Patients without symptom improvement or with partial response under medical therapy
             (at least 2 different antimuscarinic agents).

        Exclusion Criteria:

          -  Subject has a diagnostic of dysfunctional voiding

          -  Post-voiding residue > 20 cc

          -  Polyuria (> 75 ml/kg/b.w./24 hours)

          -  Nephrogenic of central diabetes insipidus

          -  Constipation at screening (if the patient is treated and the treatment is successful,
             the patient will be eligible to the study)

          -  Urinary tract infection at visit 2-3-4. If UTI is present at the screening visit, the
             UTI must be treated and the success of the treatment must be documented with a
             negative urinalysis at visit 2.

          -  QTc interval greater than 460 ms, or any increase of 30 ms on follow-up EKG (mean of 6
             separate EKG-3 from visit week-2 and 3 from visit week 0). If a patient meets those
             criteria in the first month (initial dose), he will be excluded from the study. If the
             QTc change is noted after the up-titration, the dose will be decreased and EKG will be
             repeated within 1 week to ensure normalization of QTc.

          -  Clinically significant unstable medical condition or disorder

          -  Subject is pregnant or intends to become pregnant

          -  Serum creatinin more than or equal to 2 times the upper limit of normal

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than or equal
             to 2 times ULN, or bilirubin more than or equal to 1.5 times ULN.

          -  Known hypersensitivity to mirabegron or any contraindication to the use of the
             molecule, in accordance to the product monography (to the exception of pediatric age).

          -  Subject is taking medication that interact with mirabegron and this medication can't
             be discontinued (see appendix 1 of excluded drugs)

          -  Known urological pathology other than OAB that could explain urinary symptoms (as
             bladder stone…)

          -  Non-treated or non-controlled arterial hypertension