A Phase I, Multicenter, Open-label, Single-sequence Drug-drug Interaction Study to Assess the Effect of INC280 on the Pharmacokinetics of Digoxin and Rosuvastatin in Patients With cMET-dysregulated Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 3
- 主要终点
- Tmax of digoxin and rosuvastatin
研究概览
简要总结
the study aim to assess the effect of INC280 on the pharmacokinetics of digoxin and rosuvastatin in patients with cMET-dysregulated advanced solid tumors
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have:
- •advanced solid tumors and have confirmed cMET dysregulation
- •at least one measurable lesion as defined by RECIST 1.
- •recovered from all toxicities related to prior anti-cancer therapies
- •adequate organ function
- •ECOG performance status (PS) of 0 or 1
排除标准
- •Patients must not have:
- •known hypersensitivity to any of the excipients of INC280
- •prior treatment with cMET or HGF-targeting inhibitor
- •known hypersensitivity to digoxin or rosuvastatin or its excipients
- •symptomatic central nervous system (CNS) metastases who are neurologically unstable
- •presence or history of carcinomatous meningitis
- •history of another primary malignancy that is currently clinically significant or currently requires active intervention
- •Clinically significant, uncontrolled heart diseases, including QTcF ≥ 450 msec (male patients), ≥ 460 msec (female patients) on the screening ECG
- •Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting INC280
- •Major surgery within 4 weeks prior to starting INC280
- •Patients receiving unstable or increasing doses of corticosteroids.
- •Impairment of GI function or GI disease that may significantly alter the absorption of INC280
- •Patients who have received, or are expected to receive digoxin or rosuvastatin within 21 days prior to the beginning of the DDI phase (Day 1) and for the duration of the DDI phase.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
INC280
干预措施: INC280 (Drug)
INC280
干预措施: digoxin (Drug)
INC280
干预措施: rosuvastatin (Drug)
结局指标
主要结局
Tmax of digoxin and rosuvastatin
时间窗: Up to 240 hours post digoxin and rosuvastatin dose
digoxin and rosuvastatin pharmacokinetics parameters
AUCinf of digoxin and rosuvastatin
时间窗: Up to 240 hours post digoxin and rosuvastatin dose
digoxin and rosuvastatin pharmacokinetics parameters
Cmax of digoxin and rosuvastatin
时间窗: Up to 240 hours post digoxin and rosuvastatin dose
digoxin and rosuvastatin pharmacokinetics parameters
T1/2 of digoxin and rosuvastatin
时间窗: Up to 240 hours post digoxin and rosuvastatin dose
digoxin and rosuvastatin pharmacokinetics parameters
CL/F of digoxin and rosuvastatin
时间窗: Up to 240 hours post digoxin and rosuvastatin dose
digoxin and rosuvastatin pharmacokinetics parameters
AUClast of digoxin and rosuvastatin
时间窗: Up to 240 hours post digoxin and rosuvastatin dose
digoxin and rosuvastatin pharmacokinetics parameters
Vz/F of digoxin and rosuvastatin
时间窗: Up to 240 hours post digoxin and rosuvastatin dose
digoxin and rosuvastatin pharmacokinetics parameters
Lambda_z of digoxin and rosuvastatin
时间窗: Up to 240 hours post digoxin and rosuvastatin dose
digoxin and rosuvastatin pharmacokinetics parameters
次要结局
- Adverse events based on the CTCAE v4.03 grade (severity) and other safety data (e.g.,ECG, vital signs, laboratory results)(From consent to 30 days post last dose)
- Disease control rate of patients treated with INC280(Up to 12 months)
- Overall response rate of patients treated with INC280(Up to 12 months)
- Concentration of INC280 during DDI phase(Day 22, Cycle 2 Day 1)