Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence.
OBJECTIVE
Urge urinary incontinence is the involuntary leakage of urine commonly occurring in older adults, particularly women. Preclinical evidence suggests that urge urinary incontinence may occur due to up-regulation of tachykinin mediated bladder/spinal reflex signaling. This study tested the hypothesis that aprepitant, a neurokinin-1 receptor antagonist, may be efficacious in the treatment of urge urinary incontinence.


METHODS
This was a double-blind, randomized, placebo controlled, parallel group pilot study in which postmenopausal women with a history of urge urinary incontinence or mixed incontinence (with predominantly urge urinary incontinence) were assigned to receive a 160 mg capsule of aprepitant (61) or placebo (64) once daily for 8 weeks. The primary end point was percent change from baseline in average daily micturitions assessed by a voiding diary. Secondary end points included average daily total urinary incontinence and urge urinary incontinence episodes, and urgency episodes.


RESULTS
Aprepitant significantly decreased the average daily number of micturitions compared with placebo at 8 weeks. The between-group treatment difference expressed as percent change from baseline was -6.8%, 95% CI (-12.5, -1.1) (p = 0.019). The average daily number of urgency episodes was also significantly reduced compared to placebo (p = 0.049). The average daily number of urge urinary incontinence and total urinary incontinence episodes were also reduced, although the difference was not statistically significant. Aprepitant was generally well tolerated and adverse experiences were generally mild.


CONCLUSIONS
Results of this initial study suggest that neurokinin-1 receptor antagonism may represent a novel therapeutic approach to treating overactive bladder syndrome.
Green
Stuart A
SA
Respiratory & Allergy, Merck Research Laboratories, Merck & Co. Inc., 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. stuart_green@merck.com
Alon
Achilles
A
Ianus
Juliana
J
McNaughton
Kristin S
KS
Tozzi
Carol A
CA
Reiss
Theodore F
TF
D000328:Adult; D000077608:Aprepitant; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D064729:Neurokinin-1 Receptor Antagonists; D010865:Pilot Projects; D017698:Postmenopause; D018040:Receptors, Neurokinin-1 / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D053202:Urinary Incontinence, Urge / Q000188:drug therapy*
D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D000077608:Aprepitant