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INC280 in Healthy Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function

2020年12月8日 更新者：Novartis Pharmaceuticals

An Open Label, Single-dose, Multi-center, Parallel-group, Two-staged Study to Evaluate Pharmacokinetics of Oral cMET Inhibitor INC280 in Non-Cancer Subjects With Impaired Hepatic Function and Non-Cancer Subjects With Normal Hepatic Function

This is a phase I, multi-center, open-label, single oral dose, parallel group study to evaluate the pharmacokinetics and safety of INC280 in non-cancer subjects with impaired hepatic function and non-cancer subjects with normal hepatic function.The study population will be healthy male and postmenopausal or sterile female subjects who meet all of the inclusion and none of the exclusion criteria. Subjects will be assigned to groups according to their hepatic function: normal (Group 1), mild (Group 2), moderate (Group 3), and severe (Group 4) impairment. This study consists of a two-staged design with interim analysis. In Stage 1, subjects in Groups 1, 2 and 3 will be enrolled. Upon completion of Stage 1, an interim analysis will be conducted. Depending on the results of the analysis, either the study will conclude with no further enrollment or Stage 2 will commence with enrollment of Group 4.

A minimum of 6 evaluable subjects per group will be enrolled.Once enrolled in the study, participants will be confined to the facility for 4 days, given a single dose of INC280 and monitored for pharmacokinetic and safety assessments.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

31

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • Florida
      • Miami、Florida、美国、33136
        • University of Miami Miller School of Medicine Clinical Resea Oncology
      • Miami、Florida、美国、33142
        • Clinical Pharmacology of Miami, LLC.
      • Orlando、Florida、美国、32086
        • Orlando Clinical Research Center
    • Minnesota
      • Minneapolis、Minnesota、美国、55404
        • DaVita Clinical Research
    • North Carolina
      • Durham、North Carolina、美国、27710
        • Duke University Medical Center Oncology

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 75年 (成人、年长者)

接受健康志愿者

是的

有资格学习的性别

全部

描述

Inclusion Criteria (all groups):

  • Female subjects must be postmenopausal or sterile
  • Good health, as determined by absence of clinically significant findings in medical history, physical examination, vital signs, and ECGs, unless it is consistent with known clinical disease for hepatic impairment subjects
  • Adequate organ function and normal laboratory tests, unless it is consistent with known clinical disease for hepatic impairment subjects
  • Body Mass Index (BMI) of 18- 36 kg/m2, with body weight ≥ 50 kg

Inclusion Criteria (hepatic impairment groups):

  • Confirmed liver disease
  • Stable comorbidities are allowed as long as generally considered healthy
  • Subjects with hepatic impairment must meet the following laboratory values:
  • Aspartate transaminase (AST) ≤ 5 x ULN
  • Alanine transaminase (ALT) ≤ 5 x ULN
  • Total bilirubin ≤ 3 x ULN (≤ 5 x XULN for subjects with severe hepatic impairment [group 4])
  • Calculated creatinine clearance (using Cockcroft-Gault formula) ≥ 45 mL/min
  • Platelets > 50 x 10^9/L. Subjects with severe hepatic impairment can be enrolled if platelet count > 40 x 10^9/L

Exclusion Criteria (all groups):

  • History or presence of clinically significant ECG abnormalities or clinically significant cardiovascular disease
  • Immunocompromised subjects, including HIV
  • Use of drugs known to affect CYP3A4
  • Use of QT-prolonging drugs
  • Use of any other drugs, unless they are required to treat the hepatic impairment subject's disease
  • Use of proton pump inhibitors (PPI) medications within 7 days prior to dosing and during the current study until last day of confinement

Exclusion Criteria (normal hepatic function group):

  • A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result

Exclusion Criteria (hepatic impairment groups):

  • Active Grade 3 or 4 hepatic encephalopathy within 4 weeks of study entry
  • Clinical evidence of severe ascites
  • Ascites requiring paracentesis within 3 weeks prior to dosing

Other protocol-defined inclusion/exclusion criteria may apply.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：肝功能正常
肝功能正常的受试者
药品：INC280
Single 200 mg dose INC280
实验性的：轻度肝功能损害
轻度肝功能不全的受试者
药品：INC280
Single 200 mg dose INC280
实验性的：中度肝功能损害
中度肝功能不全的受试者
药品：INC280
Single 200 mg dose INC280
实验性的：Severe hepatic impairment
Subjects with severe hepatic impairment
药品：INC280
Single 200 mg dose INC280

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
AUClast of INC280
大体时间：Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
AUCinf of INC280
大体时间：Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
Cmax of INC280
大体时间：Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
Tmax of INC280
大体时间：Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
T1/2 of INC280
大体时间：Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
CL/F of INC280
大体时间：Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose
Vz/F of INC280
大体时间：Up to 72 hours post-dose
INC280 pharmacokinetic parameters
Up to 72 hours post-dose

次要结果测量

结果测量
措施说明
大体时间
Adverse events based on the CTCAE v4.03 grade (severity) and frequency, and other safety data (e.g., ECG, laboratory results)
大体时间：Up to 30 days
Safety
Up to 30 days
Unbound fraction and AUClast based on unbound concentration in plasma
大体时间：3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and AUCinf based on unbound concentration in plasma
大体时间：3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and Cmax based on unbound concentration in plasma
大体时间：3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and Tmax based on unbound concentration in plasma
大体时间：3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and T1/2 based on unbound concentration in plasma
大体时间：3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and CL/F based on unbound concentration in plasma
大体时间：3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose
Unbound fraction and Vz/F based on unbound concentration in plasma
大体时间：3 hours post-dose
To assess the plasma protein binding of INC280
3 hours post-dose

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Novartis Pharmaceuticals

调查人员

  • 研究主任：NovartisPharmaceuticals、NovartisPharmaceuticals

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2015年6月12日

初级完成 (实际的)

2017年8月14日

研究完成 (实际的)

2017年9月12日

研究注册日期

首次提交

2015年6月9日

首先提交符合 QC 标准的

2015年6月16日

首次发布 (估计)

2015年6月17日

研究记录更新

最后更新发布 (实际的)

2020年12月10日

上次提交的符合 QC 标准的更新

2020年12月8日

最后验证

2019年3月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • CINC280A2106

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

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