临床试验/NCT06736223

NCT06736223

已完成

1 期

A Multicentric, Open-label, Non-randomized Study to Evaluate the Pharmacokinetic, Safety and Tolerability of ITF2357 Given as an Oral Single 50 mg Dose in Participants With Chronic Hepatic Impairment Relative to Matched Participants With Normal Hepatic Function

Italfarmaco4 个研究点分布在 2 个国家目标入组 24 人2025年5月28日

干预措施ITF2357

概览

阶段: 1 期
干预措施: ITF2357
疾病 / 适应症: 未指定
发起方: Italfarmaco
入组人数: 24
试验地点: 4
主要终点: Maximum plasma concentration observed (Cmax) of ITF2357
状态: 已完成
最后更新: 3个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This is a multicentric, open-label, non-randomized study to evaluate the pharmacokinetic, safety and tolerability of ITF2357 in participants with chronic hepatic impairment relative to matched participants with normal hepatic function.

详细描述

This study will evaluate the effect of mild and moderate hepatic impairment (HI) on the pharmacokinetics of ITF2357 and its metabolites. The total number of participants to be enrolled in the study is 24 subjects: * 8 Participants with mild HI (Child-Pugh class A) * 8 Participants with moderate HI (Child-Pugh class B) * 8 Participants with normal hepatic function (control group) Each participant will go through: * A screening period from Day (D)-28 to D-2 * One 6-day/5-night inpatient period (from D-1 evening to D5 morning) * An end-of-study evaluation to be done on D10 (±1 day).

注册库

euclinicaltrials.eu

开始日期

2025年5月28日

结束日期

2025年8月13日

最后更新

3个月前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Italfarmaco

责任方

Sponsor

主要研究者

Paolo Tornese

Scientific

Italfarmaco S.p.A.

入排标准

入选标准

•for Participants with HI:
•Male or female participants, between 18 and 75 years of age, inclusive.
•Body weight between 60.0 and 110.0 kg, inclusive if male, and between 50.0 and 100.0 kg, inclusive if female, body mass index (BMI) between 18.00 and 34.99 kg/m2, inclusive.
•Stable chronic liver disease assessed by medical history, physical examination, laboratory values.
•Vital signs after 10 minutes resting in supine position within the following range \[or if out of range, considered not clinically significant (NCS) by the Investigator\]:
•95 mmHg \< systolic blood pressure (SBP) \< 180 mmHg 45 mmHg \< diastolic blood pressure (DBP) \< 100 mmHg 40 bpm \< heart rate (HR) \< 100 bpm.
•12-lead ECG without clinically significant abnormality, in the judgment of the Investigator; in no circumstances should participants be enrolled with corrected QT according to Fridericia (QTcF) \> 450 ms.
•6\. Laboratory parameters within the acceptable range for participants with HI; however, serum creatinine should be strictly below the upper laboratory range.
•7\. Female participants who are not pregnant or nursing at Screening and Day -1, or who are not planning to become pregnant during study period and until 4 weeks after the IMP administration.
•8\. Female participants of non-childbearing potential, defined as one of the following:

排除标准

•for Participants with HI:
•Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecological (if female), or infectious disease, or signs of acute illness.
•Hepatocarcinoma.
•Acute hepatitis.
•Hepatic encephalopathy grade 2, 3, and
•Blood donation within 2 months before inclusion.
•Symptomatic postural hypotension, whatever the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in SBP ≥ 30 mmHg within 3 minutes when changing from supine to standing position.
•Presence or history of drug hypersensitivity, or allergic disease, except seasonal rhinitis, diagnosed and treated by a physician.
•History or presence of regular use of recreational drugs or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis) within 2 years before inclusion.
•Smoking more than 15 cigarettes or equivalent per day, unable to refrain from smoking over 5 cigarettes per day from D-1 and throughout the entire institutionalization (i.e., up to D5).

研究组 & 干预措施

Mild HI

Patients with mild HI (Child-Pugh class A)

干预措施: ITF2357

Moderate HI

Patients with moderate HI (Child-Pugh class B)

干预措施: ITF2357

Healthy Volunteers

Participants with normal hepatic function (control group)

干预措施: ITF2357

结局指标

主要结局

Maximum plasma concentration observed (Cmax) of ITF2357

时间窗: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

Area under the plasma concentration versus time curve to the real time tlast (AUClast) of ITF2357

时间窗: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

Area under the plasma concentration versus time curve extrapolated to infinity (AUC0-inf) of ITF2357

时间窗: Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose

次要结局

Time to reach Cmax (tmax) of ITF2357(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Apparent terminal half-life (t1/2) of ITF2357(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Apparent total plasma clearance from plasma (CL/F) of ITF2357(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Apparent volume of distribution (Vz/F) of ITF2357(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Maximum plasma concentration observed (Cmax) of ITF2357 metabolites(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Area under the plasma concentration versus time curve to the real time tlast (AUClast) of ITF2357 metabolites(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Area under the plasma concentration versus time curve extrapolated to infinity (AUC0-inf) of ITF2357 metabolites(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Time to reach Cmax (tmax) of ITF2357 metabolites(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Apparent terminal half-life (t1/2) of ITF2357 metabolites(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Unbound fraction (fu) of ITF2357 and its metabolites(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Unbound area under the plasma concentration time curve (AUCu) of ITF2357 and its metabolites(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Unbound maximum plasma concentration observed (Cmax,u) of ITF2357 and its metabolites(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Unbound apparent total plasma clearance (CL/Fu) of ITF2357(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Unbound apparent volume of distribution (Vz/Fu) of ITF2357(Pre-dose (30 minutes before administration), then 0.5 to 96-hour post-dose)
Electrocardiogram QT interval corrected according to Fredericia's formula (ECG QTcF)(From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration))
Incidence of Treatment Emergent Adverse Events (TEAEs)(From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration))
Severity of Treatment Emergent Adverse Events (TEAEs)(From Baseline (28 to 2 days before administration) to End of Study (9 to 11 days after administration))