Camlipixant in Refractory Chronic Cough: A Phase 2b, Randomized, Placebo-controlled Trial (SOOTHE).

Objectives: SOOTHE (NCT04678206), a phase 2b, randomized, placebo-controlledtrial, evaluated the efficacy and safety of P2X3 antagonist camlipixant in adults with refractory chronic cough (cough duration, ⩾1 yr; baseline awake cough frequency, ⩾25 coughs/h).

目的：SOOTHE（NCT04678206）是一项2b期、随机、安慰剂对照试验，评估了P2X3拮抗剂camlipixant在成人难治性慢性咳嗽患者中的疗效和安全性（咳嗽持续时间，⩾1年；基线清醒时咳嗽频率，⩾25次/小时）。

Methods: After a single-blind, 16-day placebo run-in, patients were randomized (1:1:1:1) to receive camlipixant 12.5, 50, or 200 mg twice daily or placebo for 4 weeks.

方法：在单盲、16天安慰剂洗脱期后，患者按1:1:1:1的比例随机接受camlipixant 12.5、50或200 mg每日两次或安慰剂治疗4周。

The primary endpoint was change from baseline to Day 28 in objective 24-hour cough frequency.

主要终点是从基线到第28天24小时客观咳嗽频率的变化。

Secondary endpoints included cough severity and cough-related quality of life.

次要终点包括咳嗽的严重程度和与咳嗽相关的生活质量。

Measurements and Main Results: Overall, 310 patients were randomized.

测量和主要结果：总体上，有310名患者被随机分配。

A statistically significant reduction in placebo-adjusted 24-hour cough frequency was seen in the 50 mg (-34.4%; 95% confidence interval, -50.5 to -13.3; P = 0.0033) and 200 mg (-34.2%; 95% confidence interval, -50.7 to -12.2; P = 0.0047) camlipixant arms.

在50毫克(-34.4%；95%置信区间，-50.5至-13.3；P=0.0033)和200毫克(-34.2%；95%置信区间，-50.7至-12.2；P=0.0047)卡姆利皮克沙恩组中，与安慰剂相比，24小时咳嗽频率有统计学显著性降低。

All camlipixant arms showed a trend for greater improvement in cough severity visual analog scale and Leicester Cough Questionnaire scores over placebo.

所有卡姆利皮克沙恩组在咳嗽严重程度视觉模拟量表和莱斯特咳嗽问卷评分上显示出比安慰剂更大的改善趋势。

Camlipixant was well tolerated with no serious treatment-emergent adverse events reported.

Camlipixant 耐受性良好，未报告严重治疗相关不良事件。

Taste alteration occurred in 4.8-6.5% of patients in camlipixant arms (vs. 0% with placebo); these were usually mild-moderate.

在使用 camlipixant 的患者中，4.8-6.5% 出现味觉改变（与安慰剂的 0% 相比）；这些通常是轻度至中度。

Conclusions: Camlipixant treatment reduced cough frequency and improved patient-reported outcomes in patients with refractory chronic cough, with an acceptable safety profile.

结论：Camlipixant治疗减少了难治性慢性咳嗽患者的咳嗽频率，并改善了患者的自我报告结果，具有可接受的安全性。

Clinical trial registered with www.clinicaltrials.gov (NCT04678206).

临床试验已在www.clinicaltrials.gov注册（NCT04678206）。