A study to investigate how effective and safe the study medication 'mirabegron' is and how long it stays in the body in children aged 5 to less than 18 years with symptoms of an overactive bladder

Phase 1

• Conditions: Overactive bladder (OAB); MedDRA version: 23.1Level: LLTClassification code 10059617Term: Overactive bladderSystem Organ Class: 100000004857; Therapeutic area: Body processes [G] - Biological Phenomena [G16]

• Registration Number: EUCTR2016-001767-37-DE
• Lead Sponsor: Astellas Pharma Global Development Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-06-30
• Last Update Posted: 28 August 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 432

Inclusion Criteria

Inclusion at Visit 1/Week -4 (Screening)
2. Subject has OAB defined according to the ICCS criteria.
4. Subject weighs at least 13 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 female of childbearing potential
b. Female of childbearing potential 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 agree not to 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 432
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 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
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 removed.
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, a risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS] or family history of LQTS or exercise-induced syncope) or is currently taking medication known to prolong the QT interval
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)
15 mild or moderate renal impairment (estimated glomerular filtration rate according to the modified Schwartz of < 60 mL/min per 1.73 m2)
16 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 uses any drugs that are sensitive cytochrome P450 2D6 (CYP2D6) substrates with a narrow therapeutic index, sensitive P-glycoprotein (P-gp) substrates, or moderate or strong cytochrome CYP3A4/5 or P-gp inhibitors or inducers after the start of washout
19 is using or has used prohibited prior and/or concomitant medication(s) that cannot be discontinued
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 any condition which makes the subject unsuitable for study participation
Additional Exclusion at Visit 3/Week 0 (Baseline)
26 extraordinary daytime only urinary frequency according to the ICCS definition based on the bladder e-diary
27

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified