Fesoterodine and Oxybutynin XL for Overactive Bladder Syndrome in Children
Information source: Centre Hospitalier Universitaire de Québec, CHU de Québec
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Overactive Bladder
Intervention: Fesoterodine (Drug); Oxybutynin XL (Drug)
Phase: Phase 3
Status: Enrolling by invitation
Sponsored by: Stéphane Bolduc Official(s) and/or principal investigator(s): Stéphane Bolduc, MD, Principal Investigator, Affiliation: CHU de Québec
Summary
The purpose of this study is to evaluate the tolerability of Fesoterodine and Oxytbutynin XL
and to compare their efficacy for overactive bladder syndrome in children.
Clinical Details
Official title: Efficacy and Tolerability of Fesoterodine and Oxybutynin XL for Overactive Bladder Syndrome in Children: a Comparative Study.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment
Primary outcome: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of Fesoterodine and Oxybutynin XL
Secondary outcome: Number of Participants with Improved Overactive Bladder Symptoms as a Measure of Efficacy of Fesoterodine and Oxybutynin XLNumber of urgency and urinary incontinence episodes as a Measure of Efficacy of Fesoterodine and Oxybutynin XL
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 nocturia1, 2. 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. In the last years, Fesoterodine, a new antimuscarinic, has been developed
for the treatment of OAB. Studies show significant improvement of clinical symptoms in
adults with OAB and fewer side effects. The outcomes for the pediatric population remain
unknown due to lack of studies. Antimuscarinic agents are the mainstay of the current
treatment of OAB. 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. Fesoterodine is a new antimuscarinic drug
available as a prolonged release (PR) tablet formulation, and is approved in Europe, Canada
and the USA at doses of 4 mg and 8 mg once daily for the treatment of OAB in adults; it is
not approved for use in the pediatric population. Before randomization, subjects will
undergo 2 weeks of urotherapy. At the end of these 2 weeks, the inclusion and exclusion
criteria will be reassessed and the subjects admissible for the study will be randomized for
a 8 week-treatment period during which the urotherapy will be continued. Eligible subjects
will be randomized to 8 weeks of single-blind treatment with Fesoterodine 4 mg Po Die or
Oxybutynin XL 10 mg Po Die. At the end of the 8 week-treatment period, subjects will stop
their current therapy for one week. At week 9, both cohorts will do a cross over. The cohort
on Fesoterodine will be on Oxybutynin XL and vice versa. After 4 weeks on any given
medication, the possibility of up-titration will be assessed. On a telephone interview with
the research nurse, 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 (Fesoterodine 8mg or Oxybutynin XL 20mg daily). If accepted, the
medication will be provided with instructions to report any new side effects. Oxybutynin XL
(Ditropan XL) is the extended release and once a day formulation of Oxybutynin (actual gold
standard for OAB in children). By using this formulation with children who can swallow
pills, the control group has the same once a day regimen as Fesoterodine (Toviaz), thus
avoiding this possible bias. The bid or tid immediate release formulation is known to create
more side effects and decreases the compliance (sometime hard to administer the afternoon
dose to children at school).
Subjects will complete a 3-day voiding diary prior to each medical visit to assess the
efficacy of the single-blind treatment and urotherapy. Visits will be done on week - 2, 0, 8
and 17 (+/- 5 days)
Eligibility
Minimum age: 5 Years.
Maximum age: 14 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Male or female ≥ 5 years old and ≤14 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.
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 Oxybutynin or Fesoterodine or any contraindication to the
use of those 2 molecules, in accordance to the product monography (to the exception
of pediatric age).
- Subject is taking medication that interact with Fesoterodine 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
Locations and Contacts
Additional Information
Starting date: December 2014
Last updated: August 1, 2015
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