Open-label, Multicenter, Pharmacokinetic, and Safety Study in Children (Term Newborn Infants to 23 Months of Age) Undergoing a Contrast-enhanced MRI With an Intravenous Injection of 0.1 mmol/kg BW Gadobutrol 1.0 M
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 44
- 主要终点
- Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual
研究概览
简要总结
The main purpose of this study is to collect data on the way gadobutrol is taken into, moves around, and is eliminated from, the body of children aged 0 to less than 2 years. The study will also evaluate safety and tolerability, and efficacy of gadobutrol.
A maximum total amount of approximately 5 ml of blood will be needed for these analyses which will be drawn within 2-3 days.
Gadobutrol is a contrast agent used for enhancement of Magnetic Resonance Imaging (MRI), potentially allowing better visibility of tissues in the body. Children aged under 2 years scheduled for a routine contrast-enhanced MRI examination of any body region may take part in this study, in which case they will receive gadobutrol as contrast agent intravenously at the standard dose of 0.1 mmol/kg (0.1 ml/Kg) of body weight. Only subjects without renal insufficiency of any intensity (i.e. estimated Glomerular Filtration Rate <80% of age adjusted normal value calculated based on the Schwartz formula) will be included in the trial.
The duration of this study as a whole is around 1 year and the total number of children to be enrolled is 50. A child will be expected to take part in the study for around 7 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- — 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric subjects aged <2 years (term newborn infants to toddlers 23 months of age inclusive)
- •Subject is scheduled to undergo routine gadolinium-enhanced MRI of any body region
排除标准
- •Subjects undergoing a change in chemotherapy within 48 hours prior to and up to 24 hours after gadobutrol injection
- •Any planned intervention during the study and up to 24 hours after gadobutrol injection (excluding lumbar puncture)
- •Subjects who received or will receive any investigational product within 48 hours before gadobutrol injection or during study participation
- •Subjects who received or will receive any other contrast agent within 48 hours prior to gadobutrol injection or up to 24 hours after gadobutrol injection
- •Subjects with contraindication for MRI such as iron metal implants (e.g. aneurysm clips)
- •History of anaphylactoid or anaphylactic reaction to any allergen including drugs and contrast agents
- •Subject with renal insufficiency of any intensity, i.e. estimated Glomerular Filtration Rate <80% of age adjusted normal value calculated based on the Schwartz formula
研究组 & 干预措施
Overall study
干预措施: Gadobutrol (Gadavist, BAY86-4875) (Drug)
结局指标
主要结局
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Infinity of Gadobutrol: Individual
时间窗: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC from time 0 (start of injection) to infinity was reported in micromole\*hour per liter (micromole\*h/L).
Body Weight-Normalized Total Body Clearance (CL) of Gadobutrol From Plasma: Individual
时间窗: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Clearance is the volume of the fluid presented to the eliminating organ that is effectively completely cleared of drug per unit time and depends on the rate of elimination. CL of gadobutrol normalized for body weight, was reported in Liter per hour per kilogram (L/(h\*kg).
Body Weight-Normalized Apparent Volume of Distribution at Steady State (Vss) of Gadobutrol in Plasma: Individual
时间窗: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Vss is an estimate of drug distribution independent of the elimination process and is proportional to the amount of drug in the body versus the drug plasma concentration at steady-state.
Terminal Elimination Half-Life (t1/2) of Gadobutrol From Plasma: Individual
时间窗: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
Half-life refers to the elimination of the drug, that is, the time it takes for the blood plasma concentration to reach half the concentration. Terminal elimination half-life of gadobutrol from plasma is expressed in hours and is derived from the terminal slope of the concentration versus time curve.
Simulation of Plasma Concentration of Gadobutrol at 20 Minutes Post-Injection (C20)
时间窗: 20 minutes post-injection
Simulation is the use of the model to predict data other than observed data, in this case early Gadobutrol plasma concentration after intravenous injection. Plasma concentration serves as a surrogate for efficacy (signal and contrast enhancement) in MRI. C20 was simulated for virtual pediatric subjects with homogenous distribution over age. Simulated median (5th and 95th percentile in parenthesis) gadolinium plasma concentrations for a dose of 0.1 mmol/kg body weight were presented.
Simulation of Plasma Concentration of Gadobutrol at 30 Minutes Post-Injection (C30)
时间窗: 30 minutes post-injection
Simulation is the use of the model to predict data other than observed data, in this case early Gadobutrol plasma concentration after intravenous injection. Plasma concentration serves as a surrogate for efficacy (signal and contrast enhancement) in MRI. C30 was simulated for virtual pediatric subjects with homogenous distribution over age. Simulated median (5th and 95th percentile in parenthesis) gadolinium plasma concentrations for a dose of 0.1 mmol/kg body weight were presented.
Mean Residence Time (MRT) of Gadobutrol in Plasma: Individual
时间窗: Blood samples were collected at 3 timepoints between 15 minutes and 8 hours post administration of gadobutrol
MRT is the average time that the molecules introduced into the body stay in the body. MRT of Gadobutrol is expressed in hours.
次要结局
- Number of Subjects With Anatomical Area Evaluated(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects by Overall Contrast Quality(Images were taken post-injection (within about 15 minutes))
- Number of Subjects by Overall Contrast Quality by Body Region(Images were taken post-injection (within about 15 minutes))
- Number of Subjects With Technical Adequacy for Diagnosis(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Presence of Pathology by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Technical Adequacy for Diagnosis by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Presence of Pathology(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Border Delineation of Lesion of Vessel(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Border Delineation of Lesion of Vessel by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Number of Lesions Detected(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Number of Lesions Detected by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Contrast Enhancement in Lesion or Vessel(Images were taken pre-injection and post-injection (within about 15 minutes))
- Contrast Enhancement in Lesion or Vessel by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Diagnoses by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Final Diagnosis by Body Region(Up to 4 weeks post-injection)
- Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Change in Diagnosis From Unenhanced to Combined MRI by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Change in Diagnosis From Unenhanced MRI to Final Diagnosis by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects by Visualization of Lesion-Internal Morphology or Homogeneity of Vessel Enhancement by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Diagnoses(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Additional Diagnostic Gain(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Additional Diagnostic Gain by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Confidence in Diagnosis(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Confidence in Diagnosis by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Final Diagnosis(Up to 4 weeks post-injection)
- Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Change in Diagnosis From Combined MRI to Final Diagnosis by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Change in Management From Unenhanced to Combined MRI(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Change in Management From Unenhanced to Combined MRI by Body Region(Images were taken pre-injection and post-injection (within about 15 minutes))
- Number of Subjects With Clinically Significant Abnormal Laboratory Values(Baseline (not exceeding 24 hours before Gadobutrol injection) up to 24 hours post injection)
- Estimated Glomerular Filtration Rate (eGFR) Prior to Gadobutrol Injection(Before gadobutrol injection)