A Study to Evaluate Mirabegron in Pediatric Participants From 5 to Less Than 18 Years of Age With Overactive Bladder (OAB) (Dolphin)

This is an interventional treatment trial for Overactive Bladder (OAB) focused on measuring Pediatrics, mirabegron Read More

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.