A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Mirabegron Oral Suspension in Pediatric Subjects From 3 to Less Than 12 Years of Age With Neurogenic Detrusor Overactivity (NDO) or Overactive Bladder (OAB)

• Subject is male or female from 3 to less than 12 years of age.

• Subject has a documented diagnosis according to the International Children's Continence Society (ICCS) criteria of:

  • NDO, or
  • Idiopathic OAB

• Subject's weight/height:

  • Subject must have a body weight of ≥ 15.0 kg
  • For NDO: subject is not suffering from malnutrition or is not grossly overweight, in the opinion of the Investigator
  • For OAB: subject's weight and height are within the normal percentiles (3rd to 97th percentile) according to Centers for Disease Control and Prevention (CDC) growth charts.
• Subject is able to swallow the study medication in accordance with the protocol.
• Subject and subject's parent(s)/legal guardian agree that the subject will not participate in another interventional study while on treatment.
• Subject and subject's parent(s)/legal guardian are willing and able to comply with the study requirements and with the concomitant medication restrictions.

• Female subject must:

  • Be of non-childbearing potential: Clearly pre-menarchal or in the judgment of the Investigator is pre-menarchal.
  • Or the following inclusion criteria are to be followed, if applicable (rare cases): Female subject that reached puberty must: Agree not to try to become pregnant during the study and for 28 days after the final study drug administration, And have a negative urine pregnancy test predose Day 1, And, if heterosexually active agree to consistently use 2 forms of highly effective form of birth control starting at screening and throughout the study period and for28 days after the final study drug administration.

Exclusion Criteria:

• Subject has a known history of QTc prolongation or risk of QT prolongation (e.g. hypokalemia, family history of Long QT Syndrome) and/or QTcB of > 460 ms.
• Subject has a (mean) resting pulse rate > 99th percentile [Fleming et al, 2011].
• Subject has any clinically significant ECG (electrocardiogram) abnormality.
• Subject has 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 any clinically significant or unstable medical condition or disorder which, in the opinion of the Investigator, precludes the subject from participating in the study.
• Subject has current, untreated constipation (or fecal impaction for NDO subjects). If the constipation is being consistently treated for the last month, the subject can be included.
• Subject has been administered intradetrusor botulinum toxin injections; except if given > 4 months prior to screening and symptoms reappeared comparable to those before botulinum toxin injections.
• Subject has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to 2 times the ULN or total bilirubin greater than or equal to 1.5 times the ULN.
• Subject has severe renal impairment (estimated glomerular filtration rate \< 30 mL/min (Larsson)).
• Subject has any other clinically significant out of range results of urinalysis, biochemistry or hematology.
• Subject has a history or current diagnosis of any malignancy.
• Subject has known or suspected hypersensitivity to mirabegron, other ß3-agonists, any of the excipients used in the mirabegron oral suspension formulation or previous severe hypersensitivity to any drug.
• Subject meets any of the contra indications or precautions for use of mirabegron listed in the Investigator's Brochure (IB).
• Subject has used mirabegron within 12 days of the planned Reference Day (Day -4 to Day -1).

• Subject requires ongoing treatment with any of the following prohibited medications:

  • Any anticholinergic/antimuscarinic drugs within 5 half-lives prior to planned Reference Day (Day -4 to Day -1).
  • Any drugs that are sensitive CYP2D6 substrates with a narrow therapeutic index (such as thioridazine, flecainide, propafenone, imipramine, desipramine) and sensitive P-gp substrates (such as digoxin, dabigatran) within 5 half-lives prior to the planned Reference Day (Day -4 to Day -1).
  • Any moderate or strong cytochrome CYP3A4/5 or P-gp inhibitors or inducers including natural and herbal remedies (such as itraconazole, rifampicin, phenytoin, carbamazepine, St. John's Wort, grapefruit, Seville orange) within 4 weeks (inducers only) or 5 half-lives (inhibitors only) prior to the planned Reference Day (Day -4 to Day -1).
• Subject has participated in another clinical trial and/or has taken an investigational drug within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to the planned Reference Day (Day -4 to Day -1).
• Subject's parent(s)/legal guardian is an employee of the Astellas Group, any Contract Research Organization (CRO) involved, or the Investigator site executing the study.