Intervention: Mirabegron
Trial phase: Phase 3
ATC code: G04BD12
SMILES: Nc1nc(CC(=O)Nc2ccc(CCNC[C@H](O)c3ccccc3)cc2)cs1
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 31
Group description: Participants aged 12 to < 18 years received initial dose of 25 mg of mirabegron orally once daily based on weight [PED25] on day 1. At weeks 2, 4 or 8, participant's were up-titrated to the pediatric equivalent dose of 50 mg in adults [PED50] based on the given dose titration criteria. Following week 24, participants stayed on their individual dose level until week 52 EOS or EOT.
Eligibility criteria:
Inclusion Criteria:

Subject has a body weight of greater than or equal to 11 kg.
Subject suffers from NDO confirmed by urodynamic investigation at baseline. The diagnosis of NDO must be confirmed by the presence of at least 1 involuntary detrusor contraction > 15 cm H2O from baseline detrusor pressure, and/or a decrease in compliance leading to an increase in baseline detrusor pressure of > 20 cm H2O.
Subject has been using CIC for at least 4 weeks prior to visit 1/screening.
Subject has a current indication for drug therapy to manage NDO.
Subject is able to take the study drug in accordance with the protocol

Exclusion Criteria:

Subject has a known genitourinary condition (other than NDO) that may cause overactive contractions or incontinence or kidney/bladder stones or another persistent urinary tract pathology that may cause symptoms.
Subject has one of the following gastrointestinal problems: partial or complete obstruction, decreased motility such as paralytic ileus, subjects at risk of gastric retention.
Subject has a urinary indwelling catheter within 4 weeks prior to visit 1/screening.
Subject has a surgically treated underactive urethral sphincter
Subject has vesico-ureteral reflux grade 3 to 5.
Subject has undergone bladder augmentation surgery.
Subject receives electrostimulation therapy, if started within 30 days before visit 1/screening or is expected to start during the study period. Subjects who are on an established regimen may remain on this for the duration of the study.
Subject suffers from a symptomatic urinary tract infection (UTI) at baseline (symptomatic is defined as pain, fever, hematuria, new onset foul-smelling urine). If present at visit 1/screening or diagnosed between visit 1/screening and visit 3/baseline, the UTI should be treated successfully (clinical recovery) prior to baseline. If a symptomatic UTI is present at baseline, all baseline assessments are allowed to be postponed for a maximum of 7 days until the UTI is successfully treated (clinical recovery).
Subject has a (mean) resting pulse rate > 99th percentile [Fleming et al, 2011].
Subject has an established hypertension and a systolic or diastolic blood pressure greater than the 99th percentile of the normal range determined by sex, age and height, plus 5mmHg [NIH 2005].
Subject has a risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS]; or family history of LQTS, exercise-induced syncope).
Subject has severe renal impairment (eGFR according to Larsson equation < 30 mL/min).
Subject's aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is greater than or equal to 2 times the upper limit of normal (ULN) or total bilirubin (TBL) greater than or equal to 1.5 times the ULN according to age and sex.
Subject has a history or presence of any malignancy prior to visit 1/screening.
Subject has known or suspected hypersensitivity to mirabegron, any of the excipients used in the current formulations or previous severe hypersensitivity to any drug.
Subject has participated in another clinical trial (and/or has taken an investigational drug within 30 days (or 5 half-lives of the drug, or the limit set by national law, whichever is longer) prior to visit 1/screening.

Subject uses any of the following prohibited medications (after start of washout):

Any medication, other than the study drug used, for the management of NDO;
Any drugs that are sensitive CYP2D6 substrates with a narrow therapeutic index or sensitive P-glycoprotein (P-gp) substrates
Any strong CYP3A4 inhibitors if the subject has a mild to moderate renal impairment (eGFR 30 - 89 mL/min).
Subject has been administered intravesical botulinum toxin; except if given > 4 months prior to visit 1/screening and the subject experiences symptoms comparable to those existing prior to the botulinum toxin injections.