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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02468830
Recruitment Status : Completed
First Posted : June 11, 2015
Results First Posted : June 20, 2018
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
Stéphane Bolduc, CHU de Quebec-Universite Laval

Tracking Information
First Submitted Date  ICMJE May 30, 2015
First Posted Date  ICMJE June 11, 2015
Results First Submitted Date  ICMJE November 9, 2017
Results First Posted Date  ICMJE June 20, 2018
Last Update Posted Date June 20, 2018
Study Start Date  ICMJE April 2013
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2018)
  • Improved Overactive Bladder Symptoms as a Measure of Efficacy of Mirabegron [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]
    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 [ Time Frame: Participants will be followed for duration of the study, up to 52 weeks ]
    Change in mean bladder capacity from baseline to final visit based on voiding diary.
Original Primary Outcome Measures  ICMJE
 (submitted: June 8, 2015)
Improved Overactive Bladder Symptoms as a Measure of Efficacy of Mirabegron [ Time Frame: up to 52 weeks ]
Number of urgency and urinary incontinence episodes as a Measure of Efficacy
  • Improved symptoms: Change from baseline to final voiding diary in mean volume per micturition (first micturition of the day excluded).
  • Mean number of daytime incontinence per 24 h.
  • Mean number of nighttime incontinence per 24 h.
  • Mean number of grade 2 and 3 urgency episodes (according to the CUA voiding diary; 0-3) per 24 h.
  • Mean number of micturition per 24 h.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2018)
  • Number of Participants With Cardio Vascular Safety [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]
    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 [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]
    The Patient Perception of Bladder Condition (PPBC) scale on a 6-point score scale at baseline and final visit. Explanation of possible answer:
    1. does not cause me any problems at all,
    2. causes me some very minor problems,
    3. causes me some minor problems,
    4. causes me (some) moderate problems,
    5. causes me severe problems,
    6. causes me many severe problems
  • Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Mirabegron [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2015)
  • Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Mirabegron [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]
    Side effects: the number of patients presenting side effects of grade 1, 2 and 3 (mild, moderate, severe).
    • Cardiovascular safety: mean difference in blood pressure, mean difference in heart rate, mean difference in QTcB.
    • Vital signs (blood pressure and heart rate), Increase of more than 20% of heart rate at rest Variation in blood pressure: systolic ±20 mmHg, diastolic ±15 mmHg Or symptoms suggesting it, without reaching those variations. o 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.
    • Blood tests profile comparing number of subjects with significant changes: Blood work (including hepatic and renal workups, electrolytes, Hb-Ht).
  • Improved quality of life [ Time Frame: Participants will be followed for the duration of the study, up to 52 weeks ]
    • Effectiveness will also be assessed using the Patient Perception of Bladder Condition (PPBC) scale on a 6-point scale ranging from 1 to 6, at study initiation and every visit.
    • Results will be documented based on subjective relief of symptoms and objective voiding diaries following the ICCS classification.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of Mirabegron in Pediatric Patients With Overactive Bladder
Official Title  ICMJE Prospective Pilot Study of Mirabegron in Pediatric Patients With Overactive Bladder
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Overactive Bladder
  • Urinary Incontinence
Intervention  ICMJE Drug: mirabegron
Switch treatment from antimuscarinic to study medication. A dose up-titration will be possible if well tolerated and sub-optimal efficacy.
Other Name: Myrbetriq
Study Arms  ICMJE Experimental: Mirabegron
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: Drug: mirabegron
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 21, 2016)
58
Original Estimated Enrollment  ICMJE
 (submitted: June 8, 2015)
50
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02468830
Other Study ID Numbers  ICMJE B14-06-1998
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Publication submitted
Supporting Materials: Clinical Study Report (CSR)
Time Frame: March 2018
Access Criteria: publication
Responsible Party Stéphane Bolduc, CHU de Quebec-Universite Laval
Study Sponsor  ICMJE CHU de Quebec-Universite Laval
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account CHU de Quebec-Universite Laval
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP