search
Back to results

Pilot Study of Mirabegron in Pediatric Patients With Overactive Bladder (Mirabegron)

Primary Purpose

Overactive Bladder, Urinary Incontinence

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
mirabegron
Sponsored by
CHU de Quebec-Universite Laval
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Overactive Bladder focused on measuring mirabegron, antimuscarinics, beta 3 agonist, overactive bladder, children

Eligibility Criteria

5 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female ≥ 5 years old and ≤17 years old
  • OAB diagnostic according to the International Children Continence Society (ICCS) and less than 65% of the expected mean bladder capacity for age is confirmed (30 + (age in years x 30) mL) on a 3-day voiding diary.
  • Weight and height are within the normal percentile (3rd to 97th percentile) and weight is ≥ 20 kg (3rd percentile of a 8 y.o. child, boy or girl), according to the CDC growth chart
  • Ability to swallow pills
  • Subjects/parents (vs. legal guardian) agree to participate to the following study and sign the informed consent
  • Subjects/parents (vs. legal guardian) are able to comply with the study requirements and with the medication restrictions.
  • Female subjects of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain highly effective birth control during the study. Sexually active male subjects agree to use a barrier method of birth control with female partner for the duration of the study and at least one month after ending study treatment. Sexually active male subjects agree to use a condom for the duration of the study and for at least one month after ending study treatment and the female partner to use a reliable form of birth control for the duration of the study and for at least one month after ending study treatment.
  • Patients without symptom improvement or with partial response under medical therapy (at least 2 different antimuscarinic agents) or with significantly bothersome S/E on antimuscarinics.

Exclusion Criteria:

  • Subject has a diagnostic of dysfunctional voiding
  • Post-voiding residue > 20 cc
  • Polyuria (> 75 ml/kg/b.w./24 hours)
  • Nephrogenic of central diabetes insipidus
  • Constipation at screening (if the patient is treated and the treatment is successful, the patient will be eligible to the study)
  • Urinary tract infection at visit 2-3-4. If UTI is present at the screening visit, the UTI must be treated and the success of the treatment must be documented with a negative urinalysis at visit 2.
  • QTc interval greater than 460 ms, or any increase of 30 ms on follow-up EKG (mean of 6 separate EKG-3 from visit week-2 and 3 from visit week 0). If a patient meets those criteria in the first month (initial dose), he will be excluded from the study. If the QTc change is noted after the up-titration, the dose will be decreased and EKG will be repeated within 1 week to ensure normalization of QTc.
  • Clinically significant unstable medical condition or disorder
  • Subject is pregnant or intends to become pregnant
  • Serum creatinin more than or equal to 2 times the upper limit of normal
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than or equal to 2 times ULN, or bilirubin more than or equal to 1.5 times ULN.
  • Known hypersensitivity to mirabegron or any contraindication to the use of the molecule, in accordance to the product monography (to the exception of pediatric age).
  • Subject is taking medication that interact with mirabegron and this medication can't be discontinued (see appendix 1 of excluded drugs)
  • Known urological pathology other than OAB that could explain urinary symptoms (as bladder stone…)
  • Non-treated or non-controlled arterial hypertension

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Mirabegron

    Arm Description

    Patients without symptom improvement or with partial response under intensive behavioural protocol and medical therapy (at least 2 different antimuscarinic agents) will be recruited. Patients with significantly bothersome S/E on antimuscarinics will also be included.

    Outcomes

    Primary Outcome Measures

    Improved Overactive Bladder Symptoms as a Measure of Efficacy of Mirabegron
    Percent change in the frequency of urinary incontinence episodes as a Measure of Efficacy.
    Improved Overactive Bladder Symptoms as a Measure of Efficacy of Mirabegron
    Change in mean bladder capacity from baseline to final visit based on voiding diary.

    Secondary Outcome Measures

    Number of Participants With Cardio Vascular Safety
    Cardiovascular safety: mean difference in blood pressure (Variation in blood pressure: systolic ±20 mmHg, diastolic ±15 mmHg). Parameters to be measure at each visit but particularly at visit 2 (Week 0, first dose on site), to be obtained before and 1 hour after taking the medication).
    Improved Quality of Life Using the Patient Perception of Bladder Condition (PPBC) Scale
    The Patient Perception of Bladder Condition (PPBC) scale on a 6-point score scale at baseline and final visit. Explanation of possible answer: does not cause me any problems at all, causes me some very minor problems, causes me some minor problems, causes me (some) moderate problems, causes me severe problems, causes me many severe problems
    Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Mirabegron
    Cardiovascular safety: mean difference in heart rate (variation in heart rate increase of more than 20%). Heart rate was taken at initiation of study drug, at each visit and at the study end.

    Full Information

    First Posted
    May 30, 2015
    Last Updated
    June 16, 2018
    Sponsor
    CHU de Quebec-Universite Laval
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02468830
    Brief Title
    Pilot Study of Mirabegron in Pediatric Patients With Overactive Bladder
    Acronym
    Mirabegron
    Official Title
    Prospective Pilot Study of Mirabegron in Pediatric Patients With Overactive Bladder
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2013 (undefined)
    Primary Completion Date
    January 2016 (Actual)
    Study Completion Date
    March 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    CHU de Quebec-Universite Laval

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The objective is to evaluate the efficacy and safety of mirabegron to treat urinary incontinence in children with Overactive Bladder that are refractory and/or intolerant to antimuscarinics.
    Detailed Description
    Overactive bladder (OAB) is a highly prevalent disorder in the pediatric population. This condition comprises many urinary symptoms, such as urgency, increased daytime frequency of micturition, urge incontinence and nocturia. These symptoms are especially troublesome for the pediatric patients and their family since it causes embarrassment and it limits everyday activities and impairs children's development. Furthermore, serious complications are seen if this condition is not treated properly, as urinary tract infection, vesico-ureteral reflux and dysfunctional voiding. Antimuscarinic agents are the current pharmacologic mainstay for OAB. Many side effects are reported with the clinical use of antimuscarinics. Oxybutynin is the most widely antimuscarinic agent used in the pediatric population and is the only molecule approved by Health Canada for children with OAB. However, some patients have a suboptimal response to antimuscarinic and many experience side effects. Children with OAB therefore represent a disease population with a need for an alternative effective, safe and well-tolerated therapy to help manage the overactive detrusor, reducing or preventing incontinence. Mirabegron, a β3-adrenoceptor (β3-AR) agonist approved for the treatment of OAB symptoms in the adult population, is the first of a new class of compounds with a different mechanism of action. The recommended starting dose of mirabegron is 25mg, which can be increased to 50mg, based on individual efficacy and tolerability. Side effects commonly reported with antimuscarinics were not observed more often with mirabegron than with placebo (headache 2.0%, dry mouth 2.0%, constipation 1.6%). Several Phase II and III studies have shown significant improvement in clinical OAB symptoms in adults treated with mirabegron with a favorable tolerability profile. Mirabegron has not been studied yet for pediatric patients and no recommendation with regards to its use has been issued by the manufacturer nor medical regulatory bodies. A prospective open-label study, using an adjusted-dose regimen of mirabegron (25-50mg), including pediatric patients with refractory urinary incontinence due to OAB. This protocol was approved by the investigators' research ethics board. Patients without symptom improvement or with partial response under intensive behavioural protocol and medical therapy (at least 2 different antimuscarinic agents) will be recruited. Patients with significantly bothersome S/E on antimuscarinics are also included. primary end-point is efficacy toward urinary continence and secondary end-points are tolerability and safety. The patients/parents satisfaction will also be recorded. After 8 to 12 weeks on the new medication, the possibility of up-titration will be assessed. Patients and parents will be questioned on compliance, tolerability and efficacy. If the patient is taking the medication ≥80% of the time, does not have any significant side effects and still has significant OAB symptoms, the investigators will offer a dose increase (Mirabegron 50mg daily). If accepted, the medication will be provided with instructions to report any new side effects. Subjects will complete a 3-day voiding diary prior to each medical visit to assess the efficacy of the treatment and urotherapy. Visits will be done every 3 months.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Overactive Bladder, Urinary Incontinence
    Keywords
    mirabegron, antimuscarinics, beta 3 agonist, overactive bladder, children

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    58 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Mirabegron
    Arm Type
    Experimental
    Arm Description
    Patients without symptom improvement or with partial response under intensive behavioural protocol and medical therapy (at least 2 different antimuscarinic agents) will be recruited. Patients with significantly bothersome S/E on antimuscarinics will also be included.
    Intervention Type
    Drug
    Intervention Name(s)
    mirabegron
    Other Intervention Name(s)
    Myrbetriq
    Intervention Description
    Switch treatment from antimuscarinic to study medication. A dose up-titration will be possible if well tolerated and sub-optimal efficacy.
    Primary Outcome Measure Information:
    Title
    Improved Overactive Bladder Symptoms as a Measure of Efficacy of Mirabegron
    Description
    Percent change in the frequency of urinary incontinence episodes as a Measure of Efficacy.
    Time Frame
    Participants will be followed for the duration of the study, up to 52 weeks
    Title
    Improved Overactive Bladder Symptoms as a Measure of Efficacy of Mirabegron
    Description
    Change in mean bladder capacity from baseline to final visit based on voiding diary.
    Time Frame
    Participants will be followed for duration of the study, up to 52 weeks
    Secondary Outcome Measure Information:
    Title
    Number of Participants With Cardio Vascular Safety
    Description
    Cardiovascular safety: mean difference in blood pressure (Variation in blood pressure: systolic ±20 mmHg, diastolic ±15 mmHg). Parameters to be measure at each visit but particularly at visit 2 (Week 0, first dose on site), to be obtained before and 1 hour after taking the medication).
    Time Frame
    Participants will be followed for the duration of the study, up to 52 weeks
    Title
    Improved Quality of Life Using the Patient Perception of Bladder Condition (PPBC) Scale
    Description
    The Patient Perception of Bladder Condition (PPBC) scale on a 6-point score scale at baseline and final visit. Explanation of possible answer: does not cause me any problems at all, causes me some very minor problems, causes me some minor problems, causes me (some) moderate problems, causes me severe problems, causes me many severe problems
    Time Frame
    Participants will be followed for the duration of the study, up to 52 weeks
    Title
    Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Mirabegron
    Description
    Cardiovascular safety: mean difference in heart rate (variation in heart rate increase of more than 20%). Heart rate was taken at initiation of study drug, at each visit and at the study end.
    Time Frame
    Participants will be followed for the duration of the study, up to 52 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    5 Years
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female ≥ 5 years old and ≤17 years old OAB diagnostic according to the International Children Continence Society (ICCS) and less than 65% of the expected mean bladder capacity for age is confirmed (30 + (age in years x 30) mL) on a 3-day voiding diary. Weight and height are within the normal percentile (3rd to 97th percentile) and weight is ≥ 20 kg (3rd percentile of a 8 y.o. child, boy or girl), according to the CDC growth chart Ability to swallow pills Subjects/parents (vs. legal guardian) agree to participate to the following study and sign the informed consent Subjects/parents (vs. legal guardian) are able to comply with the study requirements and with the medication restrictions. Female subjects of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain highly effective birth control during the study. Sexually active male subjects agree to use a barrier method of birth control with female partner for the duration of the study and at least one month after ending study treatment. Sexually active male subjects agree to use a condom for the duration of the study and for at least one month after ending study treatment and the female partner to use a reliable form of birth control for the duration of the study and for at least one month after ending study treatment. Patients without symptom improvement or with partial response under medical therapy (at least 2 different antimuscarinic agents) or with significantly bothersome S/E on antimuscarinics. Exclusion Criteria: Subject has a diagnostic of dysfunctional voiding Post-voiding residue > 20 cc Polyuria (> 75 ml/kg/b.w./24 hours) Nephrogenic of central diabetes insipidus Constipation at screening (if the patient is treated and the treatment is successful, the patient will be eligible to the study) Urinary tract infection at visit 2-3-4. If UTI is present at the screening visit, the UTI must be treated and the success of the treatment must be documented with a negative urinalysis at visit 2. QTc interval greater than 460 ms, or any increase of 30 ms on follow-up EKG (mean of 6 separate EKG-3 from visit week-2 and 3 from visit week 0). If a patient meets those criteria in the first month (initial dose), he will be excluded from the study. If the QTc change is noted after the up-titration, the dose will be decreased and EKG will be repeated within 1 week to ensure normalization of QTc. Clinically significant unstable medical condition or disorder Subject is pregnant or intends to become pregnant Serum creatinin more than or equal to 2 times the upper limit of normal Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than or equal to 2 times ULN, or bilirubin more than or equal to 1.5 times ULN. Known hypersensitivity to mirabegron or any contraindication to the use of the molecule, in accordance to the product monography (to the exception of pediatric age). Subject is taking medication that interact with mirabegron and this medication can't be discontinued (see appendix 1 of excluded drugs) Known urological pathology other than OAB that could explain urinary symptoms (as bladder stone…) Non-treated or non-controlled arterial hypertension

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Publication submitted
    IPD Sharing Time Frame
    March 2018
    IPD Sharing Access Criteria
    publication
    Citations:
    PubMed Identifier
    26876327
    Citation
    Blais AS, Nadeau G, Moore K, Genois L, Bolduc S. Prospective Pilot Study of Mirabegron in Pediatric Patients with Overactive Bladder. Eur Urol. 2016 Jul;70(1):9-13. doi: 10.1016/j.eururo.2016.02.007. Epub 2016 Feb 11.
    Results Reference
    result

    Learn more about this trial

    Pilot Study of Mirabegron in Pediatric Patients With Overactive Bladder

    We'll reach out to this number within 24 hrs