TRPV1 inhibition does not prevent cold dry air-elicited symptoms in non-allergic rhinitis.
BACKGROUND
The transient receptor potential vanilloid 1 (TRPV1)-expressing sensory C-fibers may play a role in the development of nasal hyper-responsiveness and symptoms of non-allergic rhinitis (NAR).


OBJECTIVE
To evaluate the effects of a TRPV1-antagonist, SB-705498, on cold dry air (CDA)-induced symptoms in patients with NAR.


METHODS
This randomized, double-blind, placebo-controlled, crossover study evaluated 14 days of once daily, topical intranasal SB-705498 12 mg in 40 patients with NAR using a CDA challenge experimental model in an environmental exposure chamber (EEC, Cetero Research, Mississauga, Ontario). The primary endpoint was total symptom score (TSS), expressed as weighted mean over 60 minutes (WM0-60) or maximum TSS at 1 hour and 24 hours postdosing.


RESULTS
Treatment with SB-705498, relative to placebo, did not improve WM0-60 or maximum TSS at 1 hour and 24 hours post-dosing on days 1 or 14. Mean (95% CI) treatment differences (SB-705498 - placebo) on day 14 were, for WM0-60 at 1 hour: -0.12 (-0.60, 0.36); for maximum TSS at 1 hour: -0.03 (-0.58, 0.51). SB-705498 had no impact on any other efficacy parameters. SB-705498 was well tolerated and pharmacokinetics analysis supported the dosing regimen.


CONCLUSIONS
SB-705498 12 mg for 14 days did not alleviate the CDA-induced symptoms of NAR. Despite engagement of the TRPV1 receptor, there was no translation to clinical efficacy, suggesting redundancy in symptom pathways.
Robert D
RD
Murdoch
Philippe
P
Bareille
Jane
J
Denyer
Amy
A
Newlands
Jane
J
Bentley
Kevin
K
Smart
Katy
K
Yarnall
Deepen
D
Patel
D000328:Adult; D003080:Cold Temperature; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012220:Rhinitis / Q000517:prevention & control*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014508:Urea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D011759:Pyrrolidines; C512301:SB 705498; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014508:Urea