The CRTH2 antagonist OC000459 reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, placebo-controlled, double-blind trial
The CRTH2 antagonist OC000459 reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, placebo-controlled, double-blind trial
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DOI：
10.1111/all.12042
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发表时间：
2012-12-01
期刊：
影响因子：
12.4
通讯作者：
Pettipher, R.
中科院分区：
文献类型：
--
作者：
Horak, F.;Zieglmayer, P.;Pettipher, R.
背景CRTH 2介导响应于前列腺素D2的Th 2细胞、嗜酸性粒细胞和嗜碱性粒细胞的活化。CRTH 2拮抗剂OC 000459先前已被证明可减轻中度持续性哮喘的气道炎症并改善肺功能。本研究的目的是确定参与CRTH 2在促进鼻和眼部症状的过敏性科目暴露于grass pollent.Methods一个单中心，随机，双盲，安慰剂对照，双向交叉研究进行了35名男性受试者过敏草花粉比较OC 000459 200 mg bid与安慰剂8天。受试者在治疗的第2天和第8天暴露于草花粉（=1400粒/m3）6 h，并在6 h期间评估鼻部症状、眼部症状、其他症状、鼻分泌物重量和动脉测压。在3周的洗脱期后，受试者再转换为替代治疗8天。该试验在临床trials.gov数据库（标识符NCT 01448902）上注册。结果在第一治疗期，与安慰剂相比，用草花粉激发后，用OC 000459治疗显著减少过敏受试者的鼻和眼症状。在给药第2天观察到显著效应，在给药第8天增加。尽管有3周洗脱期，但OC 000459的治疗作用持续至第二个治疗阶段。OC 000459的安全性特征与安慰剂相似。结论OC 000459治疗耐受性良好，导致鼻结膜炎症状显著持续减轻。
Background CRTH2 mediates activation of Th2 cells, eosinophils and basophils in response to prostaglandin D2. The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. The objective of the present study was to determine the involvement of CRTH2 in promoting nasal and ocular symptoms in allergic subjects exposed to grass pollen.Methods A single centre, randomised, double-blind, placebo-controlled, two-way crossover study was conducted in 35 male subjects allergic to grass pollen comparing OC000459 200 mg bid with placebo for 8 days. Subjects were exposed to grass pollen (=1400 grains/m3) for 6 h on the 2nd and 8th days of treatment and assessed for nasal symptoms, ocular symptoms, other symptoms, nasal secretion weight and rhinomanometry over the 6-h period. After a washout period of 3 weeks, subjects were switched to the alternative treatment for a further 8 days. The trial was registered on the clinical trials.gov database (Identifier NCT01448902).Results During the first treatment period, treatment with OC000459 significantly reduced both nasal and ocular symptoms in allergic subjects compared with placebo after challenge with grass pollen. A significant effect was observed on the 2nd day of dosing which was increased on the 8th day of dosing. The therapeutic effects of OC000459 persisted into the second treatment period despite a 3-week washout phase. The safety profile of OC000459 was similar to that of placebo.Conclusion Treatment with OC000459 was well tolerated and led to a significant and persistent reduction in the symptoms of rhinoconjunctivitis.