一项1期、单中心、开放标签、剂量递增的临床试验,旨在评估TreT在健康正常志愿者体内的药代动力学、安全性和耐受性

Peter Smith, C. Watkins, K. Kraft, M. Grant
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引用次数: 2

摘要

理由:联合治疗公司正在开发一种新的药物装置产品,包括一种干粉状制剂的曲前列地尼吸入粉(TreT)和一种小型便携式干粉吸入器,用于治疗肺动脉高压(PAH)。目的:主要目的是评估TreT在健康正常志愿者(hnv)体内的药代动力学(PK)、安全性和耐受性。方法:这是一项开放标签、单次递增剂量的研究,36名hnv被分配到6个TreT单剂量队列(30、60、90、120、150和180µg)。在下一个队列增加剂量之前,对每个队列进行TreT的安全性和耐受性评估。在TreT给药前和给药后480分钟的特定时间采集血液样本。采用经验证的分析方法分析血液样本中的曲前列汀,并采用非室室法计算PK参数。结果:共36例hnv被随机分配并给药。研究期间未发生严重不良事件(ae)、严重ae或死亡。没有ae导致受试者提前死亡。最常见的ae是咳嗽(n=11, 30.6%)和头痛(n=8, 22.2%)。生物分析证实,TreT的treprostiil血浆浓度和暴露达到临床相关浓度,与历史上Tyvaso单剂量临床研究中观察到的浓度相当。treprostiil的Cmax和AUC随剂量的增加呈线性增加。结论:总的来说,TreT是安全且耐受性良好的,并且当作为干粉吸入时产生临床相关浓度的曲前列氨酯。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A phase 1, single-center, open-label, dose-rising clinical trial to evaluate the pharmacokinetics, safety and tolerability of treprostinil inhalation powder (TreT) in healthy normal volunteers
Rationale: United Therapeutics is developing a new drug-device product comprising a dry powder formulation of treprostinil inhalation powder (TreT) and a small, portable, dry powder inhaler, to treat pulmonary arterial hypertension (PAH). Objectives: The primary objective was to evaluate the pharmacokinetics (PK), safety and tolerability of TreT in healthy normal volunteers (HNVs). Methods: This was an open-label, single ascending dose study in 36 HNVs, assigned to 6 single dose cohorts of TreT (30, 60, 90, 120, 150, and 180 µg). Safety and tolerability of TreT was evaluated in each cohort prior to escalating the dose for the next cohort. Blood samples were obtained before TreT administration and at selected times through 480 minutes post‑dose. Blood samples were analyzed for treprostinil using a validated analytical method and PK parameters were calculated using noncompartmental methods. Results: A total of 36 HNVs were randomized and dosed. There were no severe adverse events (AEs), serious AEs, or deaths during the study. No AEs led to a subject’s early termination. The most frequently reported AEs were cough (n=11, 30.6%) and headache (n=8, 22.2%). Bioanalysis confirmed that the treprostinil plasma concentrations and exposure for TreT, achieved clinically relevant concentrations comparable to those observed in historical Tyvaso single dose clinical studies. Cmax and AUC for treprostinil, increased in a linear manner with increasing dose. Conclusion: Overall, TreT was safe and well-tolerated and produced clinically relevant concentrations of treprostinil when inhaled as a dry powder.
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