A Phase I, Open Label, Single Dose, Two Parts Study in Male and Female Healthy Subjects to Assess the Safety and Pharmacokinetics of Fosnetupitant 235 mg Administered as IV Bolus and of Derived Netupitant and Netupitant Metabolites
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Study Part A: Number of Treatment-emergent Adverse Events
研究概览
简要总结
This clinical trial will include two parts, i.e., Part A and Part B.
The goal of the Part A is to define the shortest safe and tolerable duration of an intravenous injection of Fosnetupitant 235 mg solution among 4 durations tested in male and female adult healthy volunteers. In study part A, researchers will compare Fosnetupitant 235 mg solution to Akynzeo® solution.
The duration determined in Part A will be investigated in study Part B.
The Part B of the study was not performed.
详细描述
The registered product Akynzeo® (235 mg fosnetupitant/0.25 mg palonosetron) solution for intravenous injection, used before chemotherapy, is to be diluted up to a final volume of 50 mL and administered during 30 min infusion. With the aim to facilitate and improve the use of this kind of products, the Sponsor Helsinn focused on the development of a ready to use solution, not requiring additional dilutions, and to be administered as a bolus injection. The product developed by Helsinn is a liquid formulation for infusion, containing exclusively fosnetupitant 235 mg free base.
Aim of the present open label, single dose, two parts (part A and part B) phase I study is to evaluate the safety and the pharmacokinetic profile of this new product, i.e., Fosnetupitant 235 mg ready to use solution for intravenous injection. In addition, the pharmacokinetic profile of fosnetupitant, netupitant (fosnetupitant is rapidly converted in netupitant after intravenous administration) and netupitant metabolites (M1, M2 and M3) will be investigated after a 30-min infusion of the registered Akynzeo® liquid formulation.
Part A of the study:
In cohort 1, 10 healthy volunteers will receive a dose of Fosnetupitant 235 mg solution as a one single 30-min intravenous infusion and additional 10 subjects will receive a single intravenous dose of Akynzeo® solution as a one single 30-min intravenous infusion, according to a parallel group design.
In each of 3 consecutive cohorts (cohorts 2, 3 and 4), 10 healthy volunteers will receive a single intravenous dose of Fosnetupitant 235 mg solution at a predefined infusion duration and will be sequentially treated as 3 subgroups of 3, 3, and 4 subjects, respectively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Study Part A - cohort 1
Fosnetupitant free base 235 mg administered as single 30 min intravenous infusion or 235 mg fosnetupitant/0.25 mg palonosetron in 20 mL injection solution administered undiluted as a single 30 min intravenous infusion
干预措施: Akynzeo solution (Drug)
Study Part A - cohort 1
Fosnetupitant free base 235 mg administered as single 30 min intravenous infusion or 235 mg fosnetupitant/0.25 mg palonosetron in 20 mL injection solution administered undiluted as a single 30 min intravenous infusion
干预措施: Fosnetupitant 235 mg solution (Drug)
Study Part A - cohort 2
Fosnetupitant free base 235 mg administered as single 15 min intravenous infusion
干预措施: Fosnetupitant 235 mg solution (Drug)
Study Part A - cohort 3
Fosnetupitant free base 235 mg administered as single 5 min intravenous infusion
干预措施: Fosnetupitant 235 mg solution (Drug)
Study Part A - cohort 4
Fosnetupitant free base 235 mg administered as single 2 min intravenous infusion
干预措施: Fosnetupitant 235 mg solution (Drug)
结局指标
主要结局
Study Part A: Number of Treatment-emergent Adverse Events
时间窗: From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)
Number of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.
Study Part A: Number of Subjects With Treatment-emergent Adverse Events
时间窗: From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)
Number of subjects with treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.
Study Part A: Type of Treatment-emergent Adverse Events
时间窗: From screening visit (day of informed consent signature) up to 24 h after the investigational medicinal product administration (a maximum of 21 days)
Type of treatment-emergent adverse events (TEAEs) collected up to 24 h post-dose.
次要结局
- Study Part A: Systolic Blood Pressure(Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: Diastolic Blood Pressure(Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: Pulse Rate(Screening visit/day -1 (enrolment day)/day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: Weight(Screening visit (day of informed consent signature)/final visit (7 days after the treatment))
- Study Part A: Full Physical Examination Through Apparatus/Systems Check(Screening visit (day of informed consent signature)/final visit (7 days after the treatment))
- Study Part A: Short Physical Examination Through Apparatus/Systems Check(Day 2 (24 h after the end of investigational product administration))
- Study Part A: ECGs - Heart Rate(Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: ECGs - PR Interval(Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: ECGs - RR Interval(Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: ECGs - QRS Duration(Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: ECGs - QT Interval(Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: ECGs - QTcB Interval(Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: ECGs - QTcF Interval(Screening visit/ day 1 (treatment day) at pre-administration, at the end of administration and 1, 2, 4, 24 h after the end of administration/final visit (7 days after the treatment))
- Study Part A: Clinical Laboratory Tests (Blood Chemistry, Haematology, Urinalysis)(Screening visit (day of informed consent signature)/final visit (7 days after the treatment))
- Study Part A: Cmax(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: C0(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: Tmax(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: Clast(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: Tlast(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: AUC0-t(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: AUC0-24(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: Terminal Elimination Rate Constant(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: t1/2(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: Systemic Clearance(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: Vz(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)
- Study Part A: MRT(Day 1 (treatment day) at pre-administration, at 2, 5, 10, 15, 20, 30 and 45 min and at 1, 1.5, 2, 3, 4, 8, 12, 24 h after the administration)