A PHASE I, OPEN-LABEL, MULTICENTER, 3-PERIOD, FIXED-SEQUENCE STUDY TO INVESTIGATE THE EFFECT OF VEMURAFENIB ON THE PHARMACOKINETICS OF A SINGLE ORAL DOSE OF ACENOCOUMAROL IN PATIENTS WITH BRAFV600 MUTATION-POSITIVE METASTATIC MALIGNANCY
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 主要终点
- Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
研究概览
简要总结
This open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of acenocoumarol in participants with BRAFV600 mutation-positive metastatic malignancies. Participants will receive a single dose of acenocoumarol 4 mg orally on Day 1 and Day 23, vemurafenib 960 mg orally twice daily on Days 4-26. After completion of pharmacokinetic assessments on Day 26, eligible participants will have the option to continue treatment with vemurafenib as part of an extension study (GO28399 [NCT01739764]).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients, 18-70 years of age
- •Patients with either unresectable Stage IIIc or IV BRAFV600 mutation-positive metastatic melanoma or other malignant BRAFV600 mutation-positive tumor type and who have no acceptable standard treatment options
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Full recovery from any major surgery or significant traumatic injury at least 14 days prior to the first dose of study treatment
- •Adequate hematologic and end organ function
- •Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to use 2 effective methods of contraception as defined by protocol during the course of the study and for at least 6 months after completion of study treatment
排除标准
- •Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of Day 1
- •Prior anti-cancer therapy within 28 days (6 weeks for nitrosureas or mitocyn C, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment Day 1
- •Palliative radiotherapy within 2 weeks prior to first dose of study treatment Day 1
- •Experimental therapy within 4 weeks prior to first dose of study treatment Day 1
- •History of clinically significant cardiac or pulmonary dysfunction, including current uncontrolled Grade >/=2 hypertension or unstable angina
- •Current Grade >/=2 dyspnea or hypoxia or need for oxygen supplementation
- •History of myocardial infarction within 6 months prior to first dose of study treatment
- •Active central nervous system lesions (i.e. participants with radiographically unstable, symptomatic lesions)
- •History of bleeding or coagulation disorders
- •Allergy or hypersensitivity to vemurafenib or acenocoumarol formulations
- •History of malabsorption or other condition that would interfere with the enteral absorption of study treatment
- •Participants with VKORC1 mutations (1639G→A, 1173C→T) in either one allele (heterozygous)or two alleles (homozygous)
- •Participants with CYP2C9*3 mutations in either one allele (heterozygous) or two alleles (homozygous)
- •History of clinically significant liver disease (including cirrhosis), current alcohol abuse, or active hepatitis B or hepatitis C virus infection
- •Human immunodeficiency virus (HIV) infection requiring antiretroviral treatment, or AIDS-related illness
- •Pregnant or lactating women
研究组 & 干预措施
Acenocoumarol + Vemurafenib
干预措施: acenocoumarol (Drug)
Acenocoumarol + Vemurafenib
干预措施: vemurafenib (Drug)
结局指标
主要结局
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Maximum plasma concentration (Cmax)
时间窗: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Area under the concentration-time curve (AUC)
时间窗: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Time to maximum plasma concentration (Tmax)
时间窗: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Terminal half-life (t1/2)
时间窗: Pre-dose and up to 72 hours post-dose
Pharmacokinetics of single-dose acenocoumarol under conditions of vemurafenib steady-state exposure: Apparent clearance (CL/F)
时间窗: Pre-dose and up to 72 hours post-dose
次要结局
- Safety: Incidence of Adverse Events and Serious Adverse Events(approximately 1.5 years)