People with neurogenic detrusor overactivity (NDO) have poor bladder control because of how their nerves to the bladder are wired. This can cause high pressure in the bladder, causing it to leak urine by accident (incontinence). Mirabegron has already been approved for adults with bladder problems and for children 3 years and older. This study will learn if mirabegron can help young children with NDO. The children will be from 6 months to up to 3 years old. The main aim of this study is to learn if mirabegron increases how much urine the bladder holds (maximum cystometric capacity, or Maximum Cystometric Capacity \[MCC\]) in young children with NDO. An increase in MCC will prevent high pressure in the bladder. Children from 6 months to up to 3 years old who have NDO can take part. They must weigh 9 kilograms (kg) or more. They will already be fitted with a tube (catheter) in their bladder. They will use this to drain urine from their bladder regularly during the day. This is called clean intermittent catheterization (CIC). There will be 2 groups in the study. Young children who aren't taking certain medicines for NDO will be in group A. Young children who are taking certain medicines for NDO will be in group B. Children in group B will stop taking these medicines before they start taking mirabegron. Treatment in group B will be delayed to allow the medicines to be cleared from the body before they start taking mirabegron. Both groups (A and B) will have the same treatment and dose of mirabegron and will have the same checks throughout the study. Mirabegron will be squirted from a syringe into the children's mouths, followed by a sip of water. This will happen once a day for up to 52 weeks (1 year). They will start on a low dose, adjusted for their weight. The dose may be increased to a higher dose if the study doctor thinks the child will benefit from the higher dose. Children will have safety checks throughout the study. Other tests will include checking how the bladder fills and empties plus an ultrasound of the bladder area. There will be several clinic visits during the study. There will be fewer clinic visits if a child stays on the low dose of mirabegron. Then, the clinic will phone the caregiver about 1 month after the last dose of mirabegron to check if there are any further medical problems.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Participants will receive mirabegron prolonged-release microgranula-based oral suspension once daily. The initial dose of mirabegron will be based on the participant's weight. The initial low dose will be up-titrated to a higher dose at weeks 2, 4 or 8 unless the participant is determined to be effectively treated with the low dose, based on urodynamics and the participants'e-diary.
Site DE49002
Hanover, Germany
Site PH63001
Quezon, Philippines
Site PH63002
Quezon City, Philippines
Site PL48001
Gdansk, Poland
Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC)
MCC is maximum bladder capacity reached at end of filling cytometry.
Time frame: Baseline and week 24
Change from baseline in bladder compliance
Bladder compliance is calculated by change in volume divided by change in pressure during filling of the bladder.
Time frame: Baseline and weeks 4 and 24
Change from baseline in filling volume until first detrusor contraction (>15cm H2O)
Change in bladder volume calculated by urodynamic assessments.
Time frame: Baseline and weeks 4 and 24
Change from baseline in number of uninhibited detrusor contractions until leakage or until maximum 135% of age-related bladder capacity
Change in number of of uninhibited detrusor contractions is calculated by urodynamic assessments.
Time frame: Baseline and weeks 4 and 24
Change from baseline in maximum catheterized daytime volume
Based on participant e-diary.
Time frame: Baseline and up to week 52
Change from baseline in average catheterized daytime volume
Based on participant e-diary.
Time frame: Baseline and up to week 52
Change from baseline in average morning catheterized volume
E-diary measure based on first catheterization after participant wakes up.
Time frame: Baseline and up to week 52
Change from baseline in number of leakage episodes per 24 hours
Based on participant e-diary.
Time frame: Baseline and up to week 52
Change from baseline in number of dry days per 7 days
Based on participant e-diary, dry defined as leakage-free.
Time frame: Baseline and up to week 52
Acceptability by pediatric oral medicine acceptability questionnaire for caregivers (P-OMAQ-C)
The P-OMAQ-C uses a 5-point numerical rate scale to measure acceptability of use of the tablet formulation with questions related to taste, smell and administration of study medication. Acceptability questionnaires to be completed by caregivers on an electronic device.
Time frame: Baseline and weeks 4, 24 and 52
Frequency of adverse events (AE)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator and events related to the (study) procedures.
Time frame: Up to week 54
Number of Participants With Vital Sign Abnormalities and/or AEs
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to week 54
Number of participants with laboratory value abnormalities and/or AEs
Number of participants with potentially clinically significant laboratory values.
Time frame: Up to week 52
Number of participants with electrocardiogram (ECG) abnormalities and/or AEs
Number of participants with potentially clinically significant ECG values.
Time frame: Up to week 54
Number of participants with upper urinary tract ultrasound abnormalities and/or AEs
Number of participants with potentially clinically significant upper urinary tract ultrasounds.
Time frame: Up to week 52
PK of mirabegron in plasma: Area under the concentration-time curve per 24 hours (AUC24)
AUC24 will be recorded from the PK plasma samples collected.
Time frame: Up to week 52
PK of mirabegron in plasma: Concentration immediately prior to dosing (Ctrough)
Ctrough will be recorded from the PK plasma samples collected.
Time frame: Up to week 52
PK of mirabegron in plasma: Apparent clearance (CL/F)
CL/F will be recorded from the PK plasma samples collected.
Time frame: Up to week 52
PK of mirabegron in plasma: Apparent volume of distribution (VzF)
VzF will be recorded from the PK plasma samples collected.
Time frame: Up to week 52
PK of mirabegron in plasma: Maximum concentration (Cmax)
Cmax will be recorded from the PK plasma samples collected.
Time frame: Up to week 52
PK of mirabegron in plasma: Time of maximum concentration (Tmax)
Tmax will be recorded from the PK plasma samples collected.
Time frame: Up to week 52
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