Abstract
Rationale: “Nasal hyper-responsiveness” has been proposed as a key mechanism driving nasal symptoms in patients with non-allergic rhinitits (NAR). Here, we explore the potential clinical use of the selective TRPV1 antagonist, SB-705498, for treatment of symptoms of rhinitis.
Methods: Two clinical studies were conducted to assess the effect of SB-705498 on nasal responses to incrementally dosed, unilateral intranasal capsaicin challenge: In the first study, a single 400mg oral dose of SB-705498 was assessed in healthy volunteers (HVT). In the second study, 12mg of SB-705498 was administered topically to patients with non-allergic rhinitis. SB-705498 or placebo was administered according to a randomised, double blind, crossover (HVT) or parallel group (NAR) design. 1 hour post dosing, incremental capsaicin challenge (2.5, 12.5 and 50mg) was performed. Symptom scores, secretion weights, peak nasal inspiratory flow (PNIF) and mediators in nasal secretions were evaluated. Blood samples were collected for pharmacokinetic analysis.
Results: Both studies showed a clear signal for effect of SB-705498 versus placebo on the clinical endpoints following intranasal challenge with capsaicin. The relative dose potency for TSS was 3.33 (1.45, 8.26 95% CI) in HVT and 2.81 (0.78, 10.7 95% CI) in NAR patients. All other clinical endpoints (satisfying parallelism) showed approximately 2-5 fold potency shift, except PNIF in NAR patients.
Conclusion: SB-705498 inhibits capsaicin induced nasal responses in HVT and NAR. SB-705498 has potential for further development as a novel, topical intranasal medicine for treatment of rhinitis.
- © 2011 ERS