A Phase I, Multicenter, Open-label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of BKM120 in Subjects With Mild, Moderate and Severe Hepatic Impairmen
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Plasma concentration of pharmacokinctis (PK) parameter Tmax
研究概览
简要总结
To assess pharamcokinetics, safety and tolerability of a single oral dose of BKM120 in subjects with mild, moderate and severe hepatic impairment
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects should be in good health (except for additional/ specific inclusion criteria related to hepatic impaired subjects) as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests of no significance at screening
- •Subjects must weigh at least 45 kg to participate in this study, and must have a body mass index (BMI) from (18.5-35.0 kg/m2)
- •Subjects must be able to communicate well with the investigator, to understand the requirements of the study and agree to use strict contraception for 16 weeks after the last BKM120 dose
- •--Additional inclusion criteria Group 1 - control healthy subjects
- •Subjects should be matched to the hepatic impaired subjects of group 2 in gender, age (± 10 years), weight (± 20%), and BMI (±5%)
- •--Additional inclusion criteria Group 2 - hepatic impaired subjects
- •Subjects with physical signs consistent with stable hepatic impairment
- •Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment (mild , moderate or severe)
- •Subjects must be free of significant medical disorders unrelated to the subject's hepatic disorder as judged by the investigator.
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L
- •Platelet count ≥ 50 x 109 /L
- •serum creatinine ≤ 1.5 x ULN
排除标准
- •Significant illness, including infections, or hospitalization within the 2 weeks prior to dosing, except for the hepatic impaired subjects who due to their liver disease may be affected by significant medical problems which require frequent hospitalizations. Invasive systemic fungal infections need to be fully resolved prior to study entry
- •Use of tobacco products within 2 weeks prior to dosing or during the study.
- •Consumption of alcohol within 2 days prior to dosing or during the study
- •Subjects with known ongoing alcohol and or/drug abuse within 1 month prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and/or at baseline
- •Subjects not willing to avoid certain study prohibited food, drink, over the counter medicines and supplements
- •Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
- •Medical history of cardiac disease and/or clinically significant ECG abnormalities.
- •History of clinically significant hematologic, renal, endocrinologic, pulmonary cardiovascular, hepatic, or allergic disease medically documented
- •Medical history of relevant psychiatric disorders
- •Subjects with Diabetes Mellitus or subjects with glucose levels out of normal range as judge by the investigator
- •History of immunodeficiency diseases, including Human Immunodeficiency Virus (HIV), as confirmed by (HIV-1, HIV-2) test
- •Additional exclusion criteria Group 1 (matched healthy control subjects) History or presence of liver disease or liver injury as indicated by an abnormal liver function profile A positive Hepatitis C test or a positive Hepatitis B surface antigen (HBsAg)
- •Additional exclusion criteria Group 2- hepatic impaired subjects
- •Subjects with clinically significant abnormal findings, not consistent with clinical disease, upon physical examination, ECG or laboratory evaluation
- •Any evidence of progressive liver disease (within the last 4 weeks prior to the screening visit) as indicated by liver transaminases, alkaline phosphatase and GGT or a ≥ 50% worsening of serum bilirubin or prothrombin time
- •Total bilirubin > 6mg/dl
- •Subject has ascites requiring intervention
研究组 & 干预措施
Mild Hepatic Impaired Group
Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - mildly hepatically impaired
干预措施: BKM120 (Drug)
Moderate Hepatic Impaired group
Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - moderately hepatically impaired
干预措施: BKM120 (Drug)
Severe Hepatic Impaired Group
Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - Severely hepatically impaired
干预措施: BKM120 (Drug)
Control Group
Matching healthy control subjects who do not have hepatic impairment and are matched to the hepatic impaired subjects by sex, age, gender and BMI
干预措施: BKM120 (Drug)
结局指标
主要结局
Plasma concentration of pharmacokinctis (PK) parameter Tmax
时间窗: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter TMax (time to maximum concentration)
Plasma concentration of PK parameter Cmax
时间窗: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CMax (maximum concentration)
Plasma concentration of PK parameter AUC-t
时间窗: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-t (Area under the curve at specified timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s). Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response
Plasma concentration of PK parameter AUC-last
时间窗: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-last (Area under the curve at last timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s). Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response
Plasma concentration of PK parameter AUC-inf
时间窗: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-inf (Area under the curve to time infinity)
Plasma concentration of PK parameter CL/F
时间窗: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
infMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CL/F (clearance)
Plasma concentration of PK parameter Vz/F
时间窗: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
FMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter Vz/F (Volume distribution)
Plasma concentration of PK parameter terminal T 1/2
时间窗: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter terminal T 1/2 (terminal half-life)
次要结局
- measurement of plasma binding(From baseline day-1 to 15 days post dose)
- Adverse events frequency(From baseline day-1 to 30 days post dose)
- Change from baseline in laboratory parameters(From baseline day-1 to 30 days post dose)
- Change from baseline in ECG parameters(From baseline day-1 to 30 days post dose)
- Change from baseline between PK parameters and total bilirubin, prothrombin time or INR and serum albumin(From baseline day-1 to 15 days post dose)
- Adverse events severity(From baseline day-1 to 30 days post dose)