A Randomized, Double Blind, Placebo-Controlled, Single Ascending Dose Trial to Assess the Pharmacokinetics and Safety of Gadopiclenol in Japanese Healthy Volunteers Phase I Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Guerbet
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Cmax
研究概览
简要总结
This single center, single ascending dose, double blind, randomized, placebo-controlled phase I trial will include male and female Japanese healthy volunteers. Within a 4-week run-in period before inclusion in the trial, healthy volunteers will be checked for inclusion/non-inclusion criteria and will then be randomized and administered with gadopiclenol or placebo. For each healthy volunteer, there will be a confinement period of one night before the inclusion visit and 2 days post administration at the clinical unit. The healthy volunteers will return to the clinical unit for safety visit 7 days after study product administration.
In each dose group, 6 healthy volunteers (3 male and 3 female) will receive gadopiclenol and 3 healthy volunteers (2M/1F or 1M/2F) will receive placebo (physiological saline solution, 0.9% sodium chloride) in one single intravenous administration.
Dose escalation from one group to the next group will be sequential and will be allowed only if the clinical and biological safety of all healthy volunteers from the previous tested dose is acceptable. The decision will be made by a Trial Safety Review Board (TSRB), consisting in members of Guerbet team and the principal investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
To ensure that administration of the IMP is carried out under double-blind conditions, an unblinded team (nurse, technician or physician) will be responsible for preparing and administrating the IMP(s). This person will ensure non-disclosure of information.
入排标准
- 年龄范围
- 20 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A Japanese healthy volunteer is defined as being born in Japan and having both parents and four grandparents (maternal and paternal) who are ethnically Japanese and having Japanese lifestyle, including diet, as determined by participant's verbal report.
- •Good health status as determined by investigator according to past medical history, clinical examination, including 12 lead ECG, vital signs (blood pressure, pulse rate, respiratory rate and body temperature) and laboratory tests at screening and inclusion.
排除标准
- •Pregnant or breast-feeding female volunteer.
- •Having acute or chronic renal insufficiency, defined as an eGFR (estimated Glomerular Filtration Rate) <90mL/min/1.73 m2, calculated by using the Japanese coefficient-modified CKD-EPI formula.
- •With known contra-indication(s) to the use or with known sensitivity to one of the products under investigation or to drugs from a similar pharmaceutical class.
- •With known history of severe allergic or anaphylactic reactions to any allergen including drugs and contrast agents.
研究组 & 干预措施
gadopiclenol
Dose per administration: dose/volume of gadopiclenol to be administered will be calculated based on patient's weight at the dose of 0.025; 0.05 or 0.1 mmol/kg BW (depending on each group).
6 volunteers will receive gadopiclenol per group
干预措施: gadopiclenol (Drug)
Placebo
Dose per administration: similar dose (Volume/weight) as the one used for Gadopiclenol in the considered group.
3 volunteers will receive gadopiclenol per group
干预措施: Placebo (Drug)
结局指标
主要结局
Cmax
时间窗: from baseline (30 minutes before injection) to 24hours post injection
Maximum concentrations measured, value taken directly from the observed concentration-time profiles
Tmax
时间窗: from baseline (30 minutes before injection) to 24hours post injection
Time corresponding to Cmax
AUC 0-inf
时间窗: from baseline (30 minutes before injection) to 24hours post injection
Area Under the observed concentration-time Curve from zero (time of drug administration) to infinity with extrapolation of the terminal phase. It will be obtained as follows: AUC 0-inf = AUC 0-T last + (Clast / β)
CLT
时间窗: from baseline (30 minutes before injection) to 24hours post injection
Total Clearance, calculated as CLT = Dose /AUC 0-inf
t 1/2β
时间窗: from baseline (30 minutes before injection) to 24hours post injection
Terminal elimination half-life of gadopiclenol calculated as follows: t 1/2β = ln 2 / β
AUC extrap%
时间窗: from baseline(30 minutes before injection) to 24hours post injection
Percentage of extrapolation of AUC from the last observation (Tlast) to infinity calculated as follows: Percentage of extrapolation of AUC from the last observation (Tlast) to infinity calculated as follows: Percentage of extrapolation of AUC from the last observation (Tlast) to infinity calculated as follows:
Ae
时间窗: Before administration and during intervals 0-6hours, 6-24hours and 24-48hours after gadopiclenol administration
Total amount of gadopiclenol excreted in urine
CLR
时间窗: Before administration and during intervals0-6hours, 6-24hours and 24-48hours after gadopiclenol administration
Renal clearance, calculated as CLR = Ae / AUC 0-inf
Vdβ
时间窗: from baseline (30 min before injection) to 24h post injection
Volume of distribution, calculated as Vdβ = Dose / (AUC 0-inf x β)
次要结局
未报告次要终点