A Phase 3, Double blind, Randomized, Multicenter, Parallel Group, Placebo controlled Sequential Dose Titration Study to Evaluate Efficacy, Safety and Pharmacokinetics of Mirabegron in Pediatric Subjects from 5 to < 18 Years of Age with Overactive Bladder
- Conditions
- 10004994Overactive Bladder (OAB)
- Registration Number
- NL-OMON49390
- Lead Sponsor
- Astellas Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 5
Inclusion at Visit 1/Week -4 (Screening)
2. Subject has OAB defined according to the ICCS criteria.
4. Subject weighs at least 11 kg at screening.
5. Subject is able to take the IP in accordance with the protocol.
6. Subject agrees to drink an adequate fluid volume during urine collection
weekends, as instructed by the investigator.
7. Subject and subject*s parent(s)/legal guardian(s) agree that the subject
will not participate in another interventional study while participating in the
present study.
8. Subject and subject*s parent(s)/legal guardian(s) are willing and able to
comply with the study requirements and with the concomitant medication
restrictions.
9. At least 1 of the following conditions apply:
a. Not a woman of childbearing potential (WOCBP)
b. WOCBP who agrees to follow the contraceptive guidance from the time of
informed consent/assent through at least 30 days after final IP administration.
10. Female subject must agree not to breastfeed starting at screening and
throughout the study period and for 30 days after final IP administration.
11. Female subject must not donate ova starting at first dose of IP and
throughout the study period and for 30 days after final IP administration.
12. Male subject with female partner(s) of childbearing potential (including
breastfeeding partner[s]) must agree to use contraception throughout the
treatment period and for 30 days after final IP administration.
13. Male subject must not donate sperm during the treatment period and for 30
days after final IP administration.
14. Male subject with pregnant partner(s) must agree to remain abstinent or use
a condom for the duration of the pregnancy throughout the study period and for
30 days after final IP administration.
Additional Inclusion at Visit 3/Week 0 (Baseline)
15. Subject must have a micturition frequency of at least 8 times (on average)
per day, in the 7 days prior to visit 3/week 0 (baseline), as recorded in the
bladder e-diary.
16. Subject must have at least 1 daytime incontinence episode (on average) per
day, during the 7-day period before visit 3/baseline, as recorded in the
bladder e-diary.
17. Subject whose symptoms are not satisfactorily controlled with urotherapy
and still fulfills the inclusion/exclusion criteria will enter the study.
Exclusion at Visit 1/Week -4 (Screening)
1. Subject has extraordinary daytime only urinary frequency according to the
ICCS definition
* This applies to a toilet-trained child who has the frequent need to void that
is associated with small micturition volumes solely during the day
* The daytime voiding frequency is at least once per hour with an average
voided volume of < 50% of expected bladder capacity (EBC) (typically 10% to
15%)
* Incontinence is rare and nocturia is absent
Subject has
2. an uroflow indicative of pathology other than OAB
3. monosymptomatic enuresis
4. dysfunctional voiding
5. bladder outlet obstruction, except if successfully treated
6. anatomical anomalies (surgically treated or untreated) that affect lower
urinary tract function
7. Subject with hematuria on dipstick test. In the case of hematuria on
dipstick test in a female during menstruation, the test can be repeated before
randomization (after the end of menstruation)
8. Subject with diabetes insipidus
Subject has
9. kidney or bladder stones
10. suffered from chronic UTI or has had more than 3 UTIs in the 2 months prior
to visit 1/week -4 (screening)
11. a pulse > 99th percentile for age
12. stage 2 hypertension or subject has stage 1 hypertension that is not well
controlled, as defined by the 2017 American Academy of Pediatrics Clinical
Practice Guidelines
13. QTcF > 440 msec on screening ECG or a risk of QT prolongation (e.g.,
hypokalemia, long QT syndrome [LQTS] or family history of LQTS or
exercise-induced syncope)
14. Subject*s aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) is >= 2 × upper limit of normal (ULN) or total bilirubin (TBL) is >= 1.5 ×
ULN according to age and sex (subjects with Gilbert*s syndrome are excepted
from the bilirubin threshold)
Subject has
15. mild or moderate renal impairment (estimated glomerular filtration rate
according to the modified Schwartz of < 60 mL/min per 1.73 m2)
16. a symptomatic (symptoms can include pain, fever, hematuria, new onset
foul-smelling urine) UTI. Note: if the UTI is treated successfully (clinical
recovery: confirmed by dipstick test and repeated dipstick test after 14 days
[both should be negative]), the subject can be rescreened
17. a history or presence of any malignancy
18. Subject uses any drugs that are sensitive cytochrome P450 2D6 (CYP2D6)
substrates with a narrow therapeutic index or sensitive P-glycoprotein (P-gp)
substrates after the start of washout
19. Subject is using or has used prohibited prior and/or concomitant
medication(s)
Subject has
20. known or suspected hypersensitivity to mirabegron or any components of the
formulations used
21. participated in another clinical study (and/or subject has received any
investigational therapy within 30 days (or 5 half-lives of the drug, or the
limit set by national law, whichever is longer) prior to visit 1/week -4
(screening)
22. Subject received urinary catheterization within 2 weeks prior to screening
23. Constipation as defined by the Rome IV criteria that cannot be successfully
treated prior to study entry
24. Female subject who has been pregnant within 6 months prior to screening or
breastfeeding within 3 months prior to screening
25. Subject has any condition which makes the subject unsuitable for study <b
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Endpoints<br /><br>Primary<br /><br>* Change from baseline at the end of the 12 week treatment period:<br /><br>* Mean number of micturitions per 24 hours</p><br>
- Secondary Outcome Measures
Name Time Method