Extension Study of Fesoterodine for Overactive Bladder Syndrome in Children.
Condition: Overactive Bladder
MeSH terms: Urinary Bladder, Overactive
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to evaluate the long term tolerability of Fesoterodine and its
      efficacy for overactive bladder syndrome in children.
    

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. 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. This study is the extension of our ongoing protocol. 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 initial 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).

      After both cycles on OAB medication, patients will be asked to report which medication they
      preferred (least side effects, best efficacy). If they tolerated well Fesoterodine, they will
      be offered to enter FOXY2015, the 12-month extension study on Fesoterodine. If they prefer to
      continue on Ditropan XL, it will be prescribed to the patient and will be followed in regular
      clinic.

      Subjects will have completed a 3-day voiding diary prior to that medical visit to assess the
      efficacy of the single-blind treatment and urotherapy. During FOXY2014, four visits were done
      on week -2, 0, 8 and 17. If they provide informed consent, it will become Visit-5 in
      FOXY2015.

      The patient will also start the extension study at the highest well-tolerated dose of
      fesoterodine while on FOXY2014. If he was using 4mg daily, he will still have the opportunity
      to increase the dosage to 8mg daily (based on efficacy and tolerability assessed by the
      research nurse phone call after 4 weeks of treatment or at visit 6).
    

Intervention name(s): Fesoterodine
Intervention type(s): Drug
Intervention description(s): Administer medication to patients with overactive bladder
Other intervention name(s): Toviaz
Intervention MeSH terms: Fesoterodine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Children; Antimuscarinics; Antocholinergics; Overactive bladder