A Phase I, Multicenter, Open-label, Single-sequence Drug-drug Interaction Study to Assess the Effect of INC280 on the Pharmacokinetics of Midazolam and Caffeine 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
- 37
- 试验地点
- 3
- 主要终点
- Lambda_z of midazolam and caffeine
研究概览
简要总结
Drg-drug Interaction (DDI) study to assess the effect of INC280 on the pharmacokinetics of midazolam and caffeine 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 or to benzodiazepines or known intolerance and hypersensitivity to caffeine
- •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 ms (male patients), ≥ 460 ms (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 consumed, or are expected to receive or consume midazolam or caffeine-containing products (e.g., tea, coffee, cola), within 2 days prior to Day 1 and during the whole duration of the DDI phase (i.e., from Day -2 to Day 12)
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
INC280
干预措施: Caffeine (Drug)
INC280
干预措施: INC280 (Drug)
INC280
干预措施: Midazolam (Drug)
结局指标
主要结局
Lambda_z of midazolam and caffeine
时间窗: Up to 72 hours post midazolam and caffeine dose
midazolam and caffeine pharmacokinetic parameter
AUClast of midazolam and caffeine
时间窗: Up to 72 hours post midazolam and caffeine dose
midazolam and caffeine pharmacokinetic parameters
Vz/F of midazolam and caffeine
时间窗: Up to 72 hours post midazolam and caffeine dose
midazolam and caffeine pharmacokinetic parameter
AUCinf of midazolam and caffeine
时间窗: Up to 72 hours post midazolam and caffeine dose
midazolam and caffeine pharmacokinetic parameter
Cmax of midazolam and caffeine
时间窗: Up to 72 hours post midazolam and caffeine dose
midazolam and caffeine pharmacokinetic parameter
Tmax of midazolam and caffeine
时间窗: Up to 72 hours post midazolam and caffeine dose
midazolam and caffeine pharmacokinetic parameter
T1/2 of midazolam and caffeine
时间窗: Up to 72 hours post midazolam and caffeine dose
midazolam and caffeine pharmacokinetic parameter
CL/F of midazolam and caffeine
时间窗: Up to 72 hours post midazolam and caffeine dose
midazolam and caffeine pharmacokinetic parameter
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)
- Overall response rate of patients treated with INC280(Baseline, every 6 weeks)
- Disease control rate of patients treated with INC280(Baseline, every 6 weeks)