| Eligibility |
Inclusion Criteria:
- 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.
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