慢性咳嗽患者通常为女性,平均年龄约60岁。然而,P2X3受体拮抗剂Gefapixant的初始药代动力学(PK)表征,用于治疗难治性或无法解释的慢性咳嗽,在主要是年轻成年男性的健康参与者中进行。这项第一阶段研究的目的是评估安全性,耐受性,在年轻(18-55岁)和老年(65-80岁)的男性和女性中,Gefapixant的PK。
随机,双盲,进行了安慰剂对照研究.健康的成年参与者按年龄和性别分为4个队列(年轻男性/女性和老年男性/女性),并随机分为4:1(年轻成年人)或3:1(老年人),每天两次(BID)接受300mg的吉非帕西特,持续1周。随后是吉非哌生600mgBID2周或安慰剂。安全,耐受性,并对PK进行了评估。
在36名随机和治疗的参与者中,28例(100%)接受吉非帕生和6例(75%)接受安慰剂报告≥1个不良事件(AE)。Gefapixant组中最常见的与治疗相关的AE是与味道相关的。7名(25%)接受gefapixant的参与者报告了预定义的肾脏/泌尿系统不良事件(严重程度均为轻度至中度)。与年轻女性和老年人相比,年轻男性的Gefapixant暴露量普遍较低;然而,差异可能是由于估计的肾小球滤过率。
Gefapixant300-600mgBID的安全性与以前的研究基本一致。需要使用人口PK建模对吉非吡克斯PK作为年龄和性别的函数进行其他表征。
Patients with chronic cough are typically female and have a mean age of ~ 60 years. However, initial pharmacokinetic (PK) characterization of the P2X3-receptor antagonist gefapixant, developed to treat refractory or unexplained chronic cough, was performed in healthy participants who were predominantly younger adult males. The objective of this Phase 1 study was to assess the safety, tolerability, and PK of gefapixant in younger (18-55 years) and older (65-80 years) males and females.
A randomized, double-blind, placebo-controlled study was conducted. Healthy adult participants were stratified into 4 cohorts by age and sex (younger males/females and older males/females) and randomized 4:1 (younger adults) or 3:1 (older adults) to receive gefapixant 300 mg twice daily (BID) for 1 week, followed by gefapixant 600 mg BID for 2 weeks or placebo. Safety, tolerability, and PK were assessed.
Of 36 randomized and treated participants, 28 (100%) receiving gefapixant and 6 (75%) receiving placebo reported ≥ 1 adverse event (AE). The most common treatment-related AEs in the gefapixant group were taste related. Predefined renal/urologic AEs were reported by 7 (25%) participants receiving gefapixant (all mild to moderate in severity). Gefapixant exposure was generally lower in younger males compared with younger females and older adults; however, differences may have been due to estimated glomerular filtration rate.
The safety profile of gefapixant 300-600 mg BID was generally consistent with previous studies. Additional characterization of gefapixant PK as a function of age and sex using population PK modeling is warranted.