Pilot Study of Mirabegron in Pediatric Patients With Overactive Bladder

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