Summary
Background
Neurogenic detrusor overactivity (NDO) can damage the upper urinary tract leading
to chronic renal impairment. Antimuscarinic therapy is used to improve urinary incontinence
and protect the upper urinary tract in patients with NDO.
Objective
This study investigated safety and efficacy of fesoterodine, a muscarinic receptor
antagonist, in 6‒<18-year-old patients with NDO (NCT01557244).
Study design
This open-label phase 3 study included 2 pediatric cohorts. Patients in Cohort 1 (bodyweight
>25 kg) were randomized to fesoterodine 4 or 8 mg extended-release tablets or oxybutynin
XL tablets administered over the 12-week active comparator-controlled phase. The safety
extension phase evaluated fesoterodine 4 and 8 mg for a further 12 weeks, with patients
in the oxybutynin arm allocated to fesoterodine 4 or 8 mg. Patients in Cohort 2 (bodyweight
≤25 kg) were randomized to fesoterodine 2 or 4 mg extended-release beads-in-capsule
(BIC) administered over a 12-week efficacy phase and 12-week safety extension phase.
Patients with stable neurologic disease and clinically or urodynamically proven NDO
were included. The primary endpoint was change from baseline to Week 12 in maximum
cystometric bladder capacity (MCC). Secondary efficacy endpoints included detrusor
pressure at maximum bladder capacity, bladder volume at first involuntary detrusor
contraction, bladder compliance, and incontinence episodes. Safety endpoints included
adverse event incidence, and specific assessments of cognition, behavior and vision.
The pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT; fesoterodine’s active
metabolite) was determined using population-pharmacokinetic analysis.
Results
In Cohort 1 (n = 124), fesoterodine 4 and 8 mg treatment resulted in significant increases
from baseline in the primary endpoint of MCC at Week 12. In Cohort 2 (n = 57), fesoterodine
2 and 4 mg BIC treatment resulted in improvements in MCC from baseline. Fesoterodine
4 and 8 mg and fesoterodine 4 mg BIC led to improvements in some secondary efficacy
endpoints. The most common treatment-related adverse reactions were gastrointestinal
effects, such as dry mouth, which occurred more frequently with oxybutynin than fesoterodine.
No detrimental effects on visual accommodation or acuity, or on cognitive function
or behavior were observed.
Discussion
These safety and efficacy results are consistent with limited published data on fesoterodine
treatment in pediatric populations with overactive bladder or NDO. Study limitations
include the lack of placebo control and the small sample size, which limits the ability
to make formal efficacy comparisons and detect rare adverse reactions.
Conclusion
Graphical Abstract
Keywords
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Article info
Publication history
Published online: November 28, 2022
Accepted:
November 20,
2022
Received in revised form:
November 11,
2022
Received:
July 28,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
