A multicenter, double-blind, randomized, placebo controlled trial of a neurokinin-1 receptor antagonist for overactive bladder.
OBJECTIVE
Neurokinin-1 receptor dependent mechanisms may regulate urinary frequency and urgency. We conducted this study to assess the efficacy and tolerability of the neurokinin-1 receptor antagonist serlopitant vs placebo or tolterodine in patients with overactive bladder.


METHODS
This randomized, double-blind, 69-center trial enrolled adults with overactive bladder (8 or more average daily micturitions and 1 or more daily urge incontinence episodes). After a 1-week placebo run-in the patients were randomized to 8 weeks of daily 0.25, 1 or 4 mg serlopitant, 4 mg tolterodine extended release or placebo. Patients kept 7-day voiding diaries. The primary end point was change from baseline in micturitions per day. Secondary end points included urgency, total incontinence, urge incontinence episodes and incidence of dry mouth.


RESULTS
Of 557 patients randomized 476 completed the trial and had valid efficacy data for analysis. Mean change from baseline in daily micturitions was significantly greater for 0.25 (-1.1) and 4 mg (-1.1) serlopitant, and for tolterodine (-1.5) than for placebo (-0.5), but not for 1 mg serlopitant (-0.8). No serlopitant dose response was demonstrated. Tolterodine was numerically superior to all doses of serlopitant in mean micturitions per day and secondary end points. The incidence of dry mouth on serlopitant (3.3%) was comparable to placebo (4.6%) and lower than tolterodine (8.8%). Serlopitant was generally well tolerated.


CONCLUSIONS
Serlopitant (0.25 and 4 mg) significantly decreased the primary end point of daily micturitions but not the secondary end points compared with placebo. Serlopitant was generally well tolerated. Thus, NK-1 receptor antagonists may have a role in the treatment of overactive bladder but this compound does not offer advantages in efficacy compared to tolterodine.
Frenkl
Tara L
TL
Merck & Co, Inc, Whitehouse Station, New Jersey, USA. tara_frenkl@merck.com
Zhu
Haiyuan
H
Reiss
Theodore
T
Seltzer
Olga
O
Rosenberg
Elizabeth
E
Green
Stuart
S
D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D003408:Cresols / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054833:Isoindoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D064729:Neurokinin-1 Receptor Antagonists; D010665:Phenylpropanolamine / Q000627:therapeutic use*; D000068737:Tolterodine Tartrate; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
D001559:Benzhydryl Compounds; D003408:Cresols; D054833:Isoindoles; D018727:Muscarinic Antagonists; D064729:Neurokinin-1 Receptor Antagonists; C551592:serlopitant; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate