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 (Dolphin)

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    432
  • sponsor
    Astellas Pharma Global Development, Inc.
Updated on 20 October 2022
mirabegron
incontinence

Summary

The purpose of this study is to evaluate the efficacy of mirabegron in children (5 to < 12 years of age) with OAB.

This study will also evaluate the safety and tolerability of mirabegron in pediatric participants with OAB and evaluate the pharmacokinetics after multiple dose administration of mirabegron in pediatric participants with OAB.

Description

The study consists of 3 periods (Screening period/urotherapy (4 weeks); Double-blind, placebo-controlled period (12 weeks); Follow-up period (2 weeks)) for a total duration of 18 weeks.

Details
Condition Overactive Bladder (OAB), Pharmacokinetics of Mirabegron
Treatment Placebo, mirabegron
Clinical Study IdentifierNCT04641975
SponsorAstellas Pharma Global Development, Inc.
Last Modified on20 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Subject has OAB defined according to the International Children's Continence Society (ICCS) criteria
Subject weighs at least 13 kg at screening
Subject is able to take the IP in accordance with the protocol
Subject agrees to drink an adequate fluid volume during urine collection weekends
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
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
Female subject is not pregnant and at least 1 of the following conditions apply
Not a female of childbearing potential
Female of child bearing potential who agrees to follow the contraceptive guidance from the time of informed consent/assent through at least 30 days after final IP administration
Female subject must agree not to breastfeed starting at screening and throughout the
study period and for 30 days after final IP administration
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
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
Male subject must agree not donate sperm during the treatment period and for 30 days after final IP administration
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)
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
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
Subject whose symptoms are not satisfactorily controlled with urotherapy and still fulfills the inclusion/exclusion criteria will enter the study

Exclusion Criteria

Exclusion at Visit 1/Week -4 (Screening)
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 an uroflow indicative of pathology other than OAB
Subject has monosymptomatic enuresis
Subject has dysfunctional voiding
Subject has bladder outlet obstruction, except if successfully treated
Subject has anatomical anomalies (surgically treated or untreated) that affect lower urinary tract function
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)
Subject with diabetes insipidus
Subject has kidney or bladder stones
Subject has suffered from chronic UTI or has had more than 3 UTIs in the 2 months prior to visit 1/week -4 (screening)
Subject has 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
Subject has QT interval using Fridericia's correction formula (QTcF) > 440 msec on screening ECG, 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
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 mild or moderate renal impairment (estimated glomerular filtration rate according to the modified Schwartz of < 60 mL/min per 1.73 m^2)
Subject has 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
Subject has a history or presence of any malignancy
Subject uses any drugs that are sensitive cytochrome P450 2D6 (CYP2D6) substrates with a narrow therapeutic index or sensitive P-glycoprotein (P-gp) substrates, or moderate or strong cytochrome CYP3A4/5 or P-gp inhibitors or inducers after the start of washout
Subject is using or has used prohibited prior and/or concomitant medication(s) that cannot be discontinued
Subject has known or suspected hypersensitivity to mirabegron or any components of the formulations used
Subject has 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)
Subject received urinary catheterization within 2 weeks prior to screening
Subject has constipation as defined by the Rome IV criteria that cannot be successfully treated prior to study entry
Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening
Subject has any condition that makes the subject unsuitable for study participation
Additional Exclusion at Visit 3/Week 0 (Baseline)
Subject has extraordinary daytime only urinary frequency according to the ICCS definition based on the bladder e-diary
Subject has monosymptomatic enuresis confirmed by the bladder e-diary
Subject has a maximum voided volume (morning volume excluded) > expected bladder capacity (EBC) for age ([age +1] × 30) in mL, based on the bladder e-diary
Subject has polyuria defined as voided urine volumes of > 40 mL/kg baseline body weight during 24 hours or > 2.8 L urine for a child weighing ≥ 70 kg (ICCS definition), based on bladder e-diary
Subject has PVR volume > 20 mL (lowest PVR volume result) as measured by ultrasonography
Subject suffers from a symptomatic (symptoms can include pain, fever, hematuria, new onset foul-smelling urine) urinary tract infection (UTI). Note: if a symptomatic UTI is present, all visit 3/week 0 (baseline) assessments must be postponed until the UTI is successfully treated (clinical recovery: confirmed by dipstick test and repeated dipstick test after 14 days [both should be negative]), and the urotherapy should continue. The postponed visit 3/week 0 (baseline) should be within 14 days of the intended visit 3/week 0 (baseline)
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)
Subject has a pulse > 99th percentile for age
Subject has 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
Any reason that makes the subject unsuitable for study participation
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note