Neurogenic detrusor overactivity (NDO) MedDRA version: 21.1 Level: LLT Classification code 10012547 Term: Detrusor hyperreflexia System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 23.1 Level: LLT Classification code 10059617 Term: Overactive bladder System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 21.1 Level: PT Classification code 10029279 Term: Neurogenic bladder System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
Astellas Pharma Global Development Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participant is eligible for participation in the study if all of the following apply: 1. IRB/IEC approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization for US study sites) must be obtained from the participant’s LAR prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Participant is male or female and 6 months to less than 3 years of age. 3. Participant’s weight is a minimum of 6 kg. 4. Participant has a previous myelomeningocele (documented at the screening visit). 5. Participant has a diagnosis of NDO confirmed by urodynamic investigation at baseline (day 1). The diagnosis of NDO should be confirmed by the presence of = 1 involuntary detrusor contraction > 15 cm H2O from baseline detrusor pressure, and/or a decrease in bladder compliance leading to an increase in baseline detrusor pressure of > 20 cm H2O. 6. Participant has a diagnosis of DSD. 7. Participant is using CIC. 8. Participant is suitable for a regimen of 4 to 6 CICs per day, fixed for the duration of the study in the opinion of the investigator using the 7-day baseline e-diary. 9. Participant is able to swallow the study drug. 10. Participant’s LAR is willing and able to comply with the study requirements (including compliant use of the e-diary) and with the concomitant medication restrictions. 11. Participant’s LAR agree not to allow participant to participate in another interventional study while on treatment and throughout the pretreatment period. Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participant will be excluded from participation in the study if any of the following apply: Participant 1. has a bladder capacity less than 25% of expected age-related capacity, confirmed by urodynamic investigation at baseline (day 1). 2. has vesicoureteral reflux grade 3 to 5 in the opinion of the investigator. 3. has a known genitourinary condition, other than NDO, that may cause overactive contractions and/or incontinence (e.g., bladder exstrophy, urinary tract obstruction, urethral diverticulum or fistula) or kidney/bladder stones or another persistent local pathology that may cause urinary symptoms. 4. has had an indwelling urinary catheter within 4 weeks prior to the baseline visit. 5. has undergone bladder augmentation surgery. 6. with surgically corrected underactive sphincter. 7. receives electrostimulation therapy, if started within 30 days before visit 1 screening or is expected to start during the study period. Participants who are on an established regimen (defined as starting more than 30 days before visit 1 screening) may remain on this for the duration of the study. 8. has been administered intravesical botulinum toxin; except if given > 4 months prior to visit 1 screening and the participant experiences symptoms comparable to those existing prior to the botulinum toxin injections. 9. has a current symptomatic UTI confirmed by urinalysis (urine culture containing > 100,000 cfu/mL) at baseline. If at screening and start of washout a UTI is present, the participant will be eligible for enrollment if the UTI has been treatedsuccessfully prior to baseline. If a symptomatic UTI is present at baseline, all baseline assessments should be postponed for a maximum of 7 days until the UTI is successfully treated. Successful treatment is defined as a symptom free patient with a white blood cell count in the urine 440 ms (based on the QTcB mean from the screening and baseline ECG triplicates), history of QTc prolongation or risk of QT prolongation (e.g., hypokalemia, LQTS, or family history of LQTS, exercise induced syncope). 15. has severe renal impairment (eGFR < 30 mL/min per 1.73 m2 for participants 1 year of age and older; serum creatinine = 97.5th percentile for participants 6 to < 12 months of age [Table 9; Boer et al, 2010]). 16. Participant’s AST or ALT is = 2 × ULN or TBL greater than or equal to 1.5 × ULN. 17. has a current or previous history of epilepsy. 18. has a history or presence of any malignancy prior to visit 1 screening. 19. has any other clinically significant out of range results of urinalysis, biochemistry or hematology as per the investigator’s interpretation. 20. has an established hypertension and systolic or diastolic blood pressure greater than the 99th percentile of their normal range determined by gender, body size and age, plus 5 mmHg (reference for normal blood pre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To evaluate the efficacy of mirabegron prolonged-release microgranula-based suspension after multiple dose administration in the pediatric population.;Secondary Objective: ? To evaluate the additional efficacy of mirabegron prolonged-release microgranulabased suspension ? To evaluate the safety and tolerability of mirabegron prolonged release microgranulabased suspension after multiple-dose administration. ? To evaluate the PK of mirabegron prolonged-release microgranula-based suspension after multiple-dose administration;Primary end point(s): ? Change from baseline in MCC after 24 weeks of treatment (based on filling urodynamics);Timepoint(s) of evaluation of this end point: after 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Change from baseline in urodynamic measures: o Bladder compliance (?V/?P) at weeks 4 and 24 o Filling volume until first detrusor contraction (> 15 cm H2O) at weeks 4 and 24 o Number of uninhibited detrusor contractions until leakage or until maximum 135% of age-related bladder capacity ? Change from baseline in e-diary measures: o Maximum and average catheterized daytime volume o Average morning catheterized volume (based on first catheterization after participant woke up) o Number of leakage episodes (per 24 h) o Number of dry (leakage-free) days per 7 days ? Acceptability by P-OMAQ-C at weeks 4, 24, and 52 ? AEs ? Vital signs, on site and SBPM; SBPM from baseline to EOS ? Clinical laboratory tests (hematology, biochemistry, eGFR, urinalysis) ? 12-lead ECG ? Upper urinary tract ultrasound ? AUC24, Ctrough, CL/F, VZ/F, Cmax and Tmax ? Additional PK parameters may be calculated based on the model used;Timepoint(s) of evaluation of this end point: throughout and at the end of the study | — |
Countries
Belgium, Denmark, Germany, Philippines, Poland, Turkey, United States
Contacts
Public ContactClinical Trial Unit
Astellas Pharma Europe B.V.
Outcome results
None listed