A Phase 3, Double-blind, Randomized, Multicenter, Parallel Group, Placebo-controlled Sequential Dose Titration Study to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Pediatric Subjects From 5 to < 18 Years of Age With Overactive Bladder
A Phase 3, Double-blind, Randomized, Multicenter, Parallel Group, Placebo-controlled Sequential Dose Titration Study to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Pediatric Subjects From 5 to < 18 Years of Age With Overactive Bladder
The purpose of this study was to evaluate the efficacy of mirabegron in children (5 to < 12 years of age) with OAB.
This study will also evaluated the safety and tolerability of mirabegron in pediatric participants with OAB and evaluated the pharmacokinetics after multiple dose administration of mirabegron in pediatric participants with OAB.
The study consisted of 3 periods (Screening period/urotherapy (4 weeks); Double-blind, placebo-controlled period (12 weeks); Follow-up period (2 weeks)) for a total duration of 18 weeks.
Inclusion Criteria:
Subject has OAB defined according to the International Children's Continence Society (ICCS) criteria.
Subject weighs at least 13 kg at screening.
Subject is able to take the IP in accordance with the protocol.
Subject agrees to drink an adequate fluid volume during urine collection weekends.
Subject and subject's parent(s)/legal guardian(s) agree that the subject will not participate in another interventional study while participating in the present study.
Subject and subject's parent(s)/legal guardian(s) are willing and able to comply with the study requirements and with the concomitant medication restrictions.
Female subject is not pregnant and at least 1 of the following conditions apply:
Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.
Female subject must not donate ova starting at first dose of IP and throughout the study period and for 30 days after final IP administration.
Male subject with female partner(s) of childbearing potential (including breastfeeding partner[s]) must agree to use contraception throughout the treatment period and for 30 days after final IP administration.
Male subject must agree not donate sperm during the treatment period and for 30 days after final IP administration.
Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final IP administration.
Additional Inclusion at Visit 3/Week 0 (Baseline)
Exclusion Criteria:
Exclusion at Visit 1/Week -4 (Screening)
Subject has extraordinary daytime only urinary frequency according to the ICCS definition.
Subject has an uroflow indicative of pathology other than OAB.
Subject has monosymptomatic enuresis.
Subject has dysfunctional voiding.
Subject has bladder outlet obstruction, except if successfully treated.
Subject has anatomical anomalies (surgically treated or untreated) that affect lower urinary tract function.
Subject with hematuria on dipstick test. In the case of hematuria on dipstick test in a female during menstruation, the test can be repeated before randomization (after the end of menstruation).
Subject with diabetes insipidus.
Subject has kidney or bladder stones.
Subject has suffered from chronic UTI or has had more than 3 UTIs in the 2 months prior to visit 1/week -4 (screening).
Subject has stage 2 hypertension or subject has stage 1 hypertension that is not well controlled, as defined by the 2017 American Academy of Pediatrics Clinical Practice Guidelines.
Subject has QT interval using Fridericia's correction formula (QTcF) > 440 msec on screening ECG, risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS] or family history of LQTS or exercise-induced syncope) or is currently taking medication known to prolong the QT interval.
Subject's aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is ≥ 2 × upper limit of normal (ULN) or total bilirubin (TBL) is ≥ 1.5 × ULN according to age and sex (subjects with Gilbert's syndrome are excepted from the bilirubin threshold).
Subject has mild or moderate renal impairment (estimated glomerular filtration rate according to the modified Schwartz of < 60 mL/min per 1.73 m^2).
Subject has a symptomatic (symptoms can include pain, fever, hematuria, new onset foul-smelling urine) UTI. Note: if the UTI is treated successfully (clinical recovery: confirmed by dipstick test and repeated dipstick test after 14 days [both should be negative]), the subject can be rescreened.
Subject has a history or presence of any malignancy.
Subject uses any drugs that are sensitive cytochrome P450 2D6 (CYP2D6) substrates with a narrow therapeutic index or sensitive P-glycoprotein (P-gp) substrates, or moderate or strong cytochrome CYP3A4/5 or P-gp inhibitors or inducers after the start of washout.
Subject is using or has used prohibited prior and/or concomitant medication(s) that cannot be discontinued.
Subject has known or suspected hypersensitivity to mirabegron or any components of the formulations used.
Subject has participated in another clinical study (and/or subject has received any investigational therapy within 30 days (or 5 half-lives of the drug, or the limit set by national law, whichever is longer) prior to visit 1/week -4 (screening).
Subject received urinary catheterization within 2 weeks prior to screening.
Subject has constipation as defined by the Rome IV criteria that cannot be successfully treated prior to study entry.
Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
Subject has any condition that makes the subject unsuitable for study participation.
Additional Exclusion at Visit 3/Week 0 (Baseline)