| Eligibility |
Inclusion Criteria:
- Subject has a documented diagnosis of:
- Neurogenic detrusor overactivity (NDO), or
- Idiopathic overactive bladder (OAB) according to International Children's
Continence Society (ICCS) criteria.
- Subject's weight/height:
- Subject should have a body weight of = 20.0 kg (all cohorts).
- For NDO: subject is not suffering from malnutrition and is not severely
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.
- Female subject must either:
- Be of non-childbearing potential:
- Clearly pre-menarchal or in the judgment of the Investigator is pre-menarchal
- Documented surgically sterile.
- Or, if of childbearing potential: 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 pre-dose Day 1,
- And, if heterosexually active agree to consistently use two forms of highly
effective form of birth control starting at screening and throughout the study
period and for 28 days after the final study drug administration.
- Female subjects must agree not to breastfeed starting at screening and throughout the
study period, and for 28 days after the last study drug administration.
- Female subject must not donate ova starting at screening and throughout the study
period, and for 28 days after the final study drug administration.
- Male subject and their female spouse/partner who are of childbearing potential must be
using a highly effective form of contraception consisting of two forms of birth
control (one of which must be a barrier method) starting at screening and continuing
throughout the study period, and for 28 days after the final study drug
administration.
- Male subject must not donate sperm starting at Screening and throughout the study
period, and for 90 days after study drug administration.
- 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
Exclusion Criteria At Screening:
- Subject is pregnant.
- Subject has a known history of QTc prolongation or risk of QT prolongation (e.g.
hypokalemia, family history of Long QT Syndrome).
- Subject has an abnormal (mean) pulse rate according to the ranges specified below: age
5 to less than 8 years: < 60 bpm or > 110 bpm; age 8 to less than 12 years: < 55 bpm
or > 100 bpm; age 12 to less than 18 years: < 50 bpm or > 100 bpm.
- Subject has any clinically significant ECG abnormality.
- Subject has mean systolic blood pressure greater than the 95th percentile according to
age and height and/or greater than 140 mmHg [National Institute of Health, 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 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater
than or equal to 2 times the upper limit of normal (ULN) or total bilirubin greater
than or equal to 1.5 times the ULN.
- Subject has severe renal impairment (estimated glomerular filtration rate (MDRD) < 30
mL/min).
- 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 OCAS tablet formulation or previous severe
hypersensitivity to any drug.
- Subject meets any of the contra-indications or precautions for use of mirabegron as
mentioned in the Investigator's Brochure (IB).
- Subject has used mirabegron in the past (last intake less than 12 days before 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 5
half-lives prior to the planned reference day (Day -4 to Day -1).
- Subject has a positive urinary drug screen test for drugs of abuse.
- Subject donated blood or blood products within 3 months prior to planned 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.
- Subject has current, untreated constipation (or fecal impaction for NDO patients). 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.
Exclusion Criteria At day 1:
- Subject has a positive urinary drug screen test for drugs of abuse.
- Subject has a positive alcohol breath test.
- Subject has used mirabegron in the past (last intake less than 24 days before planned
reference day (Day -4 to Day -1).
- Subject requires ongoing treatment with any of the following prohibited medications:
- Any anticholinergics/antimuscarinics within 5 half-lives prior to intake of the
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 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) within 5 half-lives prior to reference
day (Day -4 to Day -1).
- Subject donated blood or blood products within 3 months prior to Day 1.
- Subject (female subjects of childbearing potential) has a positive urinary pregnancy
test.
- Subject has a current symptomatic urinary tract infection.
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