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A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam in Patients With ALK-positive Advanced Tumors

2020年12月16日 更新者：Novartis Pharmaceuticals

A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam Administered as a Two-drug Cocktail in Patients With ALK-positive Advanced Tumors Including Non-small Cell Lung Cancer (NSCLC)

The purpose of this study was to evaluate the potential inhibitory effects of ceritinib on the CYP3A4- and CYP2C9-mediated metabolism of the probe drugs midazolam and warfarin, respectively, when administered simultaneously as a cocktail. The results obtained from this drug interaction study would provide guidance that would enable an update to the ceritinib labeling and ouldl help guide recommendations for administration of co-medications in future clinical trials.

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)

33

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

  • 丹麦
      • Copenhagen、丹麦、DK-2100
        • Novartis Investigative Site
  • 意大利
    • MI
      • Milano、MI、意大利、20133
        • Novartis Investigative Site
      • Rozzano、MI、意大利、20089
        • Novartis Investigative Site
    • MO
      • Modena、MO、意大利、41124
        • Novartis Investigative Site
    • PD
      • Padova、PD、意大利、35100
        • Novartis Investigative Site
  • 美国
    • Michigan
      • Detroit、Michigan、美国、48202-2689
        • Henry Ford Hospital SC
      • Detroit、Michigan、美国、48201
        • Karmanos Cancer Institute Oncology Department
    • Texas
      • San Antonio、Texas、美国、78229
        • Cancer Therapy & Research Center UT Health Science Center SC-4
  • 西班牙
      • Madrid、西班牙、28046
        • Novartis Investigative Site
      • Madrid、西班牙、28050
        • Novartis Investigative Site
    • Galicia
      • La Coruna、Galicia、西班牙、15006
        • Novartis Investigative Site

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 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of stage IIIB (and is not a candidate for definitive multimodality therapy) or stage IV NSCLC demonstrated ALK-positive or an advanced tumor, other than NSCLC, that carries an ALK genetic alteration (mutation, translocation or amplification) and/or ALK overexpression that has progressed despite standard therapy, or for which no effective standard therapy exists.

  • The test to confirm ALK-positivity may be performed in archival tumor (obtained at or since the time of diagnosis), or in a newly obtained tumor sample taken prior to the first day of study drug. Results confirming ALK-positive status must be available before initiating treatment with ceritinib.
  • Patients who have received prior chemotherapy, other ALK inhibitors, biologic therapy, or other investigational agents, must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03) prior to starting study drug. Patients with grade ≤ 2 peripheral neuropathy or any grade of alopecia, nail changes or skin changes are allowed to enter the study.
  • Patients who have been treated with chemotherapy, with biological therapy or other investigational agent must have discontinued the treatment at least 2 weeks (14 days) prior to starting the study drug on Study Day 1.In case last chemotherapy contained nitrosourea or mitomycin C, the treatment was discontinued at least 6 weeks prior to starting study drug.
  • Patient has the ability to understand and provide signed informed consent.

Exclusion Criteria:

  • Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate), midazolam and warfarin as described in the local product information.
  • History of carcinomatous meningitis.
  • Presence or history of a malignant disease other than an ALK-positive advanced tumor that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
  • Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
  • Unstable angina within 6 months prior to screening.
  • Myocardial infarction within 6 months prior to screening.
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV).
  • Uncontrolled hypertension defined by a Systolic Blood Pressure ≥ 160 mmHg and/or Diastolic Blood Pressure ≥ 100 mmHg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication (s) was allowed prior to screening.
  • Ventricular arrhythmias.
  • Supraventricular and nodal arrhythmias not controlled with medication.
  • Other cardiac arrhythmia not controlled with medication.
  • Corrected QT (QTcF) > 470 ms using Fridericia's correction on the screening electrocardiogram (ECG) (as mean of triplicate ECGs).
  • Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mmHg, with or without anti-hypertensive medication.
  • Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).

Other Protocol defined Inclusion/Exclusion may applied.

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：其他
  • 分配：不适用
  • 介入模型：单组作业
  • 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：色瑞替尼
药品：华法林
药品：咪达唑仑
药品：ceritinib

研究衡量的是什么？

主要结果指标

结果测量
大体时间
Phamacokinetics (PK) parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not limited to: AUCinf
大体时间：Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to: AUC
大体时间：Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 121 days until death or up to 24 months.
Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 121 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to:Cmax
大体时间：Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
PK parameters of probe drugs and their metabolites in the absence or presence of ceritinib dosing, including but not lastlimited to:Tmax
大体时间：Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.

次要结果测量

结果测量
措施说明
大体时间
Ctrough concentrations of ceritinib
大体时间：Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Number of participants with Adverse Events as a measure of safety and tolerability
大体时间：Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
This will be done by looking at the vital signs, lab values and ECG
Days 1,2,3,4,5,6,7,28,29,30,31,32,33,34 and once every 21 days until death or up to 24 months.
Objective Response Rate (ORR)
大体时间：Baseline, every 6 weeks until week 27
Tumor evaluation will be determined locally by investigator per RECIST 1.1
Baseline, every 6 weeks until week 27
Duration of Response (DOR)
大体时间：Baseline, every 6 weeks until week27
Tumor evaluation will be determined locally by investigatorper RECIST 1.1
Baseline, every 6 weeks until week27

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

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。

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10月23日

初级完成 (实际的)

2017年12月12日

研究完成 (实际的)

2017年12月12日

研究注册日期

首次提交

2015年3月16日

首先提交符合 QC 标准的

2015年4月16日

首次发布 (估计)

2015年4月21日

研究记录更新

最后更新发布 (实际的)

2020年12月19日

上次提交的符合 QC 标准的更新

2020年12月16日

最后验证

2019年7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

  • CLDK378A2103
  • 2014-003741-95 (EudraCT编号)

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

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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