E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
-neurogenic detrusor overactivity (NDO)
-overactive bladder (OAB) |
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E.1.1.1 | Medical condition in easily understood language |
-not being able to control urination (incontinence)
-strong urge to urinate |
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E.1.1.2 | Therapeutic area | Body processes [G] - Biological Phenomena [G16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012547 |
E.1.2 | Term | Detrusor hyperreflexia |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
E.1.2 | System Organ Class | 100000004857 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the pharmacokinetics of mirabegron OCAS tablets after single-dose administration at different dose levels in children and adolescents with NDO or OAB. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of mirabegron OCAS tablets after single-dose administration at different dose levels in children and adolescents with NDO or OAB.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations must be obtained from the subject and/or from the subject’s parent(s) or legal guardian(s) prior to any study-related procedures (including discontinuation of prohibited medication, if applicable); assent by the subject is given as required by local law.
2. Subject is male or female from 5 to less than 18 years of age.
3. Subject has a documented diagnosis of:
- Neurogenic detrusor overactivity (NDO), or
- Idiopathic overactive bladder (OAB) according to International Children’s Continence Society (ICCS) criteria.
4. 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
5. Subject is able to swallow the study medication in accordance with the protocol.
6. Subject and subject’s parent(s)/legal guardian agree that the subject will not participate in another interventional study while on treatment.
7. Subject and subject’s parent(s)/legal guardian are willing and able to comply with the study requirements and with the concomitant medication restrictions.
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E.4 | Principal exclusion criteria |
1. Subject is pregnant.
2. Subject has a known history of QTc prolongation or risk of QT prolongation (e.g. hypokalemia, family history of Long QT Syndrome).
3. 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.
4. Subject has any clinically significant ECG abnormality.
5. 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]
6. Subject has severe renal impairment (estimated glomerular filtration rate (revised Schwartz) < 30 mL/min).
7. Subject has any other clinically significant out of range results of urinalysis, biochemistry or hematology.
8. Subject has a history or current diagnosis of any malignancy.
9. 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.
10. Subject has used mirabegron in the past (last intake less than 24 days before planned reference day (Day -4 to Day -1).
11. 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).
12. Subject has a positive urinary drug screen test for drugs of abuse.
13. 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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E.5 End points |
E.5.1 | Primary end point(s) |
Cmax, tmax, AUCinf, t1/2 . Additional PK-parameters may be calculated based on the model used. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, Day 2, Day 3-5, Day 4-7 |
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E.5.2 | Secondary end point(s) |
Nature, frequency and severity of adverse events, clinical laboratory evaluations (hematology, biochemistry, urinalysis), vital signs (including 24h holter HR), ECG (including interval measurements), physical examination, post-void residual volume (PVR) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day-28, Day-4 to Day-1, Day 1, Day 2, Day 3-5, Day 4-7 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Mirabegron is marketed under Betmiga,used for adults.This trial is to find out doses for 5-18 yrs |
Mirabegron is marketed under Betmiga,used for adults.This trial is to find out doses for 5-18 yrs |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
Germany |
Norway |
Poland |
Serbia |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last subject’s last protocol-defined assessment will mark the end of the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |