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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Allergy, Asthma & Clinical Immunology 1/2017

Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies

Zeitschrift:
Allergy, Asthma & Clinical Immunology > Ausgabe 1/2017
Autoren:
Paul Ratner, Charles P. Andrews, Frank C. Hampel, Bruce Martin, Dale E. Mohar, Denis Bourrelly, Parisa Danaietash, Sara Mangialaio, Jasper Dingemanse, Abdel Hmissi, Jay van Bavel
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13223-017-0183-z) contains supplementary material, which is available to authorized users.

Abstract

Background

Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks.

Methods

A Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season. Both were prospective, randomized, double-blind, placebo- and active-referenced (cetirizine) studies. The Phase 2 trial assessed setipiprant 100–1000 mg b.i.d. and 1000 mg o.d. versus placebo in adult and elderly participants. The Phase 3 trial assessed setipiprant 1000 mg b.i.d. in adolescent, adult, and elderly participants. Efficacy was assessed using daytime nasal symptom scores (DNSS), night-time nasal symptom scores (NNSS) and daytime eye symptom scores (DESS).

Results

579 participants were randomized in the Phase 2 trial (mean age 41.6–43.4 years); 630 were randomized in the Phase 3 trial (mean age 37.5–40.7 years). A statistically significant, dose-related improvement in mean change from baseline DNSS was observed over 2 weeks with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 trial (−0.15 [95% CI −0.29, −0.01]; p = 0.030). Setipiprant 1000 mg b.i.d. had no significant effect on this endpoint in the Phase 3 trial (−0.02 [95% CI −0.12, 0.07]; p = 0.652). Total and individual NNSS and DESS symptom scores were significantly improved with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 but not the Phase 3 trial. Setipiprant showed a favorable safety/tolerability profile.

Conclusions

The Phase 2 trial was the first large clinical study to assess a CRTH2 antagonist in seasonal AR in a real-life setting. Setipiprant dose-related efficacy in the Phase 2 trial was not confirmed during Phase 3. Setipiprant was well tolerated in both studies.
Trial registration NCT01241214 and NCT01484119
Zusatzmaterial
Additional file 1: Figure S1. Patient disposition in a) Phase 2 trial and b) Phase 3 trial.
Additional file 2: Figure S2. Overall pollen counts by day prior to and during Phase 2 and Phase 3 trials.
Additional file 3: Table S1. Setipiprant trough plasma concentrations across dose groups at the end* of weeks 1 and 2 during Phase 2 and Phase 3 trials.
Literatur
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