An Open-label, Two-cycle, Single Sequence, Self-controlled Study Evaluating Effects of Oral Itraconazole or Efavirenz on Pharmacokinetic Profiles of TGRX-326
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Plasma Tmax
研究概览
简要总结
This is a drug-drug interaction study for TGRX-326 to evaluate the effects of CYP3A inhibitor/inducer drugs on pharmacokinetic profiles of TGRX-326, an ALK inhibitor indicated for treatment of Non-small cell lung cancer.
详细描述
This study is designed as an open-label, single sequence, self-controlled study. The study will be conducted for 2 cycles, 10 days per cycle. Itraconazole, a CYP3A inhibitor, and Efavirenz, a CYP3A inducer, will be administrated orally with TGRX-326 to evaluate the effect of these drugs on the pharmacokinetic profiles of TGRX-326. Pharmacokinetic parameters will be evaluated as primary endpoints. Safety evaluation will also be conducted.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •healthy subject; male or female
- •Age between 18 and 45 (inclusive)
- •body mass index (BMI) between 19.0 and 26.0 (inclusive)
- •agree to consent
- •able to communicate with investigator well and complete the study according to study protocol
排除标准
- •abnormal and clinically significant test results (including physical exam, laboratory tests, 12-lead ECG, chest x-ray, etc.)
- •any one positive result for hepatitis-B surface antigen, Hepatitis C antibody, HIV antibody or syphilis antibody
- •prolongation in QT interval
- •use of substance that affects CYP3A4 enzyme activity with 30 days before screening
- •use of any drug within 14 days of test article administration
- •use of any investigational drug or participation of any clinical study within 3 months before screening
- •vaccination within 14 days before first test article administration, or have plans to receive vaccination during the study period
- •history of cardiovascular diseases
- •history of mental conditions including depression, aggressive behaviours, epilepsy, etc.
- •history of major surgery within 6 months before screen, or have unhealed surgical wounds.
- •any clinically significant conditions that investigator believes could affect study outcomes
- •history of allergic reactions, or allergic to any components to the study drugs, or have food allergy/special requirement for food that forbids the subject to follow food requirements for the study
- •daily cigarette consumption of more than 5 within 3 months before screening, or cannot avoid using cigarette/tabacco products during the study
- •history of alcohol abuse (more than 14 units of alcohol per week) within 3 months before screening, or alcohol breath test of > 0.0 mg/dl at screening
- •history of substance abuse, or positive drug results at screening
- •history of certain food intake 2 weeks before screening, and/or use of more than 8 cups of tea/coffee/grapefruit juice
- •positive pregnancy test results, or pregnant/breast-feeding females
- •history of unprotected sexual activities within 1 month before screening
- •have plans for child bearing during study period and for 6 months after study, or disagree to take contraceptive measures during study period and for 6 months after study
- •history of blood donation or blood loss within 3 months before screening, or have plans to donate blood within 1 month after the study
- •any reasons that is deemed unsuitable for study participation as determined by investigator
研究组 & 干预措施
Itraconazole
healthy subjects will be given Itraconazole 200 mg orally with TGRX-326 60 mg
干预措施: Itraconazole+TGRX-326 (Drug)
Efavirenz
healthy subjects will be given Efavirenz 600 mg orally with TGRX-326 60 mg
干预措施: Efavirenz+TGRX-326 (Drug)
结局指标
主要结局
Plasma Tmax
时间窗: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Time to maximum concentration of TGRX-326 measured in plasma
Plasma AUC(0-t)
时间窗: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Area Under drug concentration-time curve (AUC) from time 0 to last measureable timepoint for TGRX-326 as measured in plasma
T1/2
时间窗: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Plasma half-life of TGRX-326
Plasma AUC(0-inf)
时间窗: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Area Under drug concentration-time curve from time 0 to infinity for TGRX-326 as measured in plasma
Plasma volume of distribution (Vz/F)
时间窗: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Apparent volume of distribution of TGRX-326 in plasma
Plasma clearance (CL/F)
时间窗: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Apparent clearance of TGRX-326 in plasma
Plasma Cmax
时间窗: Itraconazole group: Day 1, Days 2-6, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Days 2-6, Day 20, Day 21-24 and Day 25 (or last day of dosing)
Maximum concentration of TGRX-326 measured in plasma
次要结局
- Adverse events/serious adverse events(through completion of the study, an average of 1 month)
- Corrected QT Interval(At screening; Itraconazole group: Day 1, Days 2-5, Day 11, Days 12-15 and Day 16 (or last day of dosing); Efavirenz group: Day 1, Day 20 and Day 25 (or last day of dosing))