背景:P2X3受体拮抗剂似乎具有治疗难治性慢性咳嗽患者的潜力。在这个双盲中,随机化,安慰剂对照研究,我们调查了疗效,安全,新型选择性P2X3受体拮抗剂filapixant(BAY1902607)在难治性慢性咳嗽患者中的耐受性。
方法:在交叉设计之后,23例难治性慢性咳嗽患者(年龄:60.4±9.1岁)在一个时期(20、80、150和250mg,每天两次,4天/3天)和安慰剂。主要疗效终点是每个给药步骤第4天的24小时咳嗽频率。Further,评估主观咳嗽严重程度和健康相关生活质量.
结果:Filapixant剂量≥80mg时可显著降低咳嗽频率和严重程度,改善咳嗽健康相关生活质量。与安慰剂相比,24小时咳嗽频率的降低范围为17%(80mg剂量)至37%(250mg剂量),从23%(80mg)降低至41%(250mg)(安慰剂:6%)。100毫米视觉模拟量表上咳嗽严重程度的降低范围为8毫米(80毫克)至21毫米(250毫克)。没有报告严重或严重的不良事件或导致停止治疗的不良事件。味觉相关不良事件发生率为4%,13%,43%,57%的患者接受了20、80、150和250毫克的filapixant治疗,分别,12%的人接受安慰剂治疗。
结论:Filapixant被证明是有效的,安全,除了味觉紊乱的发生,特别是在较高的剂量-在短期治疗干预期间耐受性良好。临床试验注册EudraCT,eudract.EMA.欧罗巴。欧盟,2018-000129-29;ClinicalTrials.gov,NCT03535168。
BACKGROUND: P2X3 receptor antagonists seem to have a promising potential for treating patients with refractory chronic cough. In this double-blind, randomized, placebo-controlled
study, we investigated the efficacy, safety, and tolerability of the novel selective P2X3 receptor antagonist filapixant (BAY1902607) in patients with refractory chronic cough.
METHODS: Following a crossover design, 23 patients with refractory chronic cough (age: 60.4 ± 9.1 years) received ascending doses of filapixant in one period (20, 80, 150, and 250 mg, twice daily, 4-days-on/3-days-off) and placebo in the other. The primary efficacy endpoint was the 24-h cough frequency on Day 4 of each dosing step. Further, subjective cough severity and health-related quality of life were assessed.
RESULTS: Filapixant at doses ≥ 80 mg significantly reduced cough frequency and severity and improved cough health-related quality of life. Reductions in 24-h cough frequency over placebo ranged from 17% (80 mg dose) to 37% (250 mg dose), reductions over baseline from 23% (80 mg) to 41% (250 mg) (placebo: 6%). Reductions in cough severity ratings on a 100-mm visual analog scale ranged from 8 mm (80 mg) to 21 mm (250 mg). No serious or severe adverse events or adverse events leading to discontinuation of treatment were reported. Taste-related adverse events occurred in 4%, 13%, 43%, and 57% of patients treated with filapixant 20, 80, 150, and 250 mg, respectively, and in 12% treated with placebo.
CONCLUSIONS: Filapixant proved to be efficacious, safe, and-apart from the occurrence of taste disturbances, especially at higher dosages-well tolerated during the short therapeutic intervention. Clinical
trial registration EudraCT, eudract.ema.europa.eu, 2018-000129-29; ClinicalTrials.gov, NCT03535168.