open-label phase 3 study with mirabegron in children from 3 to less than 18 years of age with neurogenic detrusor overactivity

Conditions: Neurogenic Detrusor Overactivity

Summary: the objective of the study was to evaluate the efficacy, safety, tolerability and pharmacokinetics of mirabegron after multiple-dose administration in the pediatric population.

this was a phase 3, open-label, baseline-controlled, multicenter study. the study consisted of 3 periods: pretreatment period: for a maximum of 28 days before baseline, including screening, washout (if applicable) and baseline. efficacy treatment period: beginning the day after baseline and continuing to week 24. long-term safety period: beginning after week 24 and continuing to week 52 (end of study \[eos\]), or to the end of treatment (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.

Keywords: pediatrics urodynamics mirabegron phase 3 neurogenic detrusor overactivity