A Phase I, Randomised, Open-Label, Single-Dose, Two-Treatment, Two-Way Crossover, Two-Stage Study to Evaluate the Bioequivalence of Onivyde (Irinotecan Liposome Injection) Manufactured at Two Different Sites Administered in Combination With Anti-Cancer Agents in Adult Participants With Metastatic Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Ipsen
- 入组人数
- 177
- 试验地点
- 36
- 主要终点
- Maximum (peak) plasma drug concentration (Cmax) of encapsulated irinotecan for Test relative to and Reference product
研究概览
简要总结
The aim of this study is to compare Onivyde manufactured at two different production sites in adult participants with advanced cancer in the pancreas.
Adult participants with metastatic pancreatic adenocarcinoma will receive Test Product (TP) and Reference Product (RP) Onivyde in line with its approved indication. The order in which they receive them depends on the group to which they are randomly assigned, this will be referred to as the crossover phase.
The average study duration for each participant until end of crossover phase is estimated to be approximately 3 months. After completion of the crossover phase, participants who in the opinion of the investigator will benefit from the treatment will be offered to enter the extension phase where they will receive the commercial Onivyde (RP) until disease progression, withdrawal, unacceptable toxicity or death. Metastatic pancreatic adenocarcinoma is a cancer that has spread (metastasized) beyond the area of the pancreas to other organs of the body.
Onivyde is approved for the treatment of metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy, in combination with 5-fluorouracil (5-FU) and leucovorin (LV).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Sequence RT: Reference Product followed by Test Product
Cycle 1 (Crossover Phase) Day 1: One dose Onivyde® Reference product + 5-FU/LV.
Cycle 1 (Crossover Phase) Day 15: One dose Onivyde Test product + 5-FU/LV
Cycle 2 Onwards (Extension Phase): Participants who choose to continue treatment after Cycle 1 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV
干预措施: Irinotecan liposome injection (Drug)
Sequence RT: Reference Product followed by Test Product
Cycle 1 (Crossover Phase) Day 1: One dose Onivyde® Reference product + 5-FU/LV.
Cycle 1 (Crossover Phase) Day 15: One dose Onivyde Test product + 5-FU/LV
Cycle 2 Onwards (Extension Phase): Participants who choose to continue treatment after Cycle 1 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV
干预措施: Folinic Acid (Drug)
Sequence RT: Reference Product followed by Test Product
Cycle 1 (Crossover Phase) Day 1: One dose Onivyde® Reference product + 5-FU/LV.
Cycle 1 (Crossover Phase) Day 15: One dose Onivyde Test product + 5-FU/LV
Cycle 2 Onwards (Extension Phase): Participants who choose to continue treatment after Cycle 1 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV
干预措施: 5-Fluorouracil (Drug)
Sequence TR: Test Product followed by Reference Product
Cycle 1 (Crossover Phase) Day 1: One dose Onivyde Test product + 5-FU/LV.
Cycle 1 (Crossover Phase) Day 15: One dose Onivyde® Reference product + 5-FU/LV.
Cycle 2 Onwards (Extension Phase): Participants who choose to continue treatment after Cycle 1 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV.
干预措施: Irinotecan liposome injection (Drug)
Sequence TR: Test Product followed by Reference Product
Cycle 1 (Crossover Phase) Day 1: One dose Onivyde Test product + 5-FU/LV.
Cycle 1 (Crossover Phase) Day 15: One dose Onivyde® Reference product + 5-FU/LV.
Cycle 2 Onwards (Extension Phase): Participants who choose to continue treatment after Cycle 1 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV.
干预措施: Folinic Acid (Drug)
Sequence TR: Test Product followed by Reference Product
Cycle 1 (Crossover Phase) Day 1: One dose Onivyde Test product + 5-FU/LV.
Cycle 1 (Crossover Phase) Day 15: One dose Onivyde® Reference product + 5-FU/LV.
Cycle 2 Onwards (Extension Phase): Participants who choose to continue treatment after Cycle 1 will receive Onivyde® Reference product on Day 1 and Day 15 of every 28-day cycle in combination with 5-FU/LV.
干预措施: 5-Fluorouracil (Drug)
结局指标
主要结局
Maximum (peak) plasma drug concentration (Cmax) of encapsulated irinotecan for Test relative to and Reference product
时间窗: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Area under the plasma concentration-time curve from time 0 to time t (AUC(0-t) of encapsulated irinotecan for Test relative to Reference product
时间窗: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞) of encapsulated irinotecan for Test relative to Reference product
时间窗: Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose))
次要结局
- Apparent volume of distribution (VZ) of encapsulated and total irinotecan for Test and Reference products(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Percentage of participants with clinically significant abnormal values(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Maximum (peak) plasma drug concentration (Cmax) of total irinotecan for Test relative to Reference product(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Area under the plasma concentration-time curve from time 0 to time t (AUC(0-t)) of total irinotecan for Test relative to Reference product(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)) of total irinotecan for Test relative to Reference product(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Time to maximum plasma concentration (Tmax) of encapsulated and total irinotecan over 15-days for each Test and Reference products(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Apparent clearance of drug from plasma (CL) of encapsulated and total irinotecan for Test and Reference products(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Terminal half-life (t1/2) of encapsulated and total irinotecan for Test and Reference products(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Apparent terminal elimination rate constant (λZ) of encapsulated and total irinotecan for Test and Reference products(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))
- Percentage of participants with treatment-emergent adverse events (TEAEs) treatment-related leading to discontinuations, or to death(Crossover Phase (From Cycle 1 Day 1 to Day 28 and Cycle 1 Day 29 (pre-dose)))