Pilot Study of Mirabegron in Pediatric Patients With Overactive Bladder
Condition: Overactive Bladder; Urinary Incontinence
MeSH terms: Urinary Incontinence; Urinary Bladder, Overactive
Intervention: mirabegron
Intervention description: Switch treatment from antimuscarinic to study medication. A dose up-titration will be possible if well tolerated and sub-optimal efficacy.
Intervention MeSH terms: Mirabegron
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 58.0
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 mirabegron to treat urinary
      incontinence in children with Overactive Bladder that are refractory and/or intolerant 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) or with significantly bothersome S/E on
             antimuscarinics.

        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