A Study to Evaluate Mirabegron in Pediatric Participants From 5 to Less Than 18 Years of Age With Overactive Bladder (OAB)
Condition: Overactive Bladder (OAB); Pharmacokinetics of Mirabegron
MeSH terms: Urinary Bladder, Overactive
Intervention: Mirabegron; Placebo
Intervention description: Oral/ Oral Suspension: Participants with a body weight of ≥ 35 kg are to receive the tablet form of IP unless unable to swallow tablets and will be provided the oral suspension as an alternative. Participants with a body weight < 35 kg or those who cannot be dosed with the tablet will receive oral suspension.; Oral/ Oral Suspension
Intervention MeSH terms: Mirabegron
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 26.0
Sex: All
Minimum age: 5 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Pediatrics; mirabegron

Summary:

      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.
    

Eligibility criteria:

        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:

               -  Not a female of childbearing potential

               -  Female of child bearing potential who agrees to follow the contraceptive guidance
                  from the time of informed consent/assent through at least 30 days after final IP
                  administration.

          -  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)

          -  Subject must have a micturition frequency of at least 8 times (on average) per day, in
             the 7 days prior to visit 3/week 0 (baseline), as recorded in the bladder e-diary.

          -  Subject must have at least 1 daytime incontinence episode (on average) per day, during
             the 7-day period before visit 3/baseline, as recorded in the bladder e-diary.

          -  Subject whose symptoms are not satisfactorily controlled with urotherapy and still
             fulfills the inclusion/exclusion criteria will enter the study.

        Exclusion Criteria:

        Exclusion at Visit 1/Week -4 (Screening)

          -  Subject has extraordinary daytime only urinary frequency according to the ICCS
             definition.

               -  This applies to a toilet-trained child who has the frequent need to void that is
                  associated with small micturition volumes solely during the day.

               -  The daytime voiding frequency is at least once per hour with an average voided
                  volume of < 50% of expected bladder capacity (EBC) (typically 10% to 15%).

               -  Incontinence is rare and nocturia is absent.

          -  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)

          -  Subject has extraordinary daytime only urinary frequency according to the ICCS
             definition based on the bladder e-diary.

          -  Subject has monosymptomatic enuresis confirmed by the bladder e-diary.

          -  Subject has a maximum voided volume (morning volume excluded) > expected bladder
             capacity (EBC) for age ([age +1] × 30) in mL, based on the bladder e-diary.

          -  Subject has polyuria defined as voided urine volumes of > 40 mL/kg baseline body
             weight during 24 hours or > 2.8 L urine for a child weighing ≥ 70 kg (ICCS
             definition), based on bladder e-diary.

          -  Subject has PVR volume > 20 mL (lowest PVR volume result) as measured by
             ultrasonography.

          -  Subject suffers from a symptomatic (symptoms can include pain, fever, hematuria, new
             onset foul-smelling urine) urinary tract infection (UTI). Note: if a symptomatic UTI
             is present, all visit 3/week 0 (baseline) assessments must be postponed until the UTI
             is successfully treated (clinical recovery: confirmed by dipstick test and repeated
             dipstick test after 14 days [both should be negative]), and the urotherapy should
             continue. The postponed visit 3/week 0 (baseline) should be within 14 days of the
             intended visit 3/week 0 (baseline).

          -  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 has a pulse > 99th percentile for age.

          -  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.

          -  Any reason that makes the subject unsuitable for study participation.