An Open-label, Single Dose, Multicenter Study to Evaluate the Pharmacokinetics and Safety of 50 mg Oral Buparlisib in Subjects With Moderate and Severe Renal Impairment Compared to Matched Control Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Plasma pharmacokinetic (PK) parameter Cmax
研究概览
简要总结
To characterize the pharmacokinetics and safety of buparlisib following a single 50 mg oral dose in subjects with moderate and severe renal impairment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Other than renal impairment, subjects should be in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, (except for additional inclusion criteria for renal impaired patients).
- •Subjects must have a BMI between 18 kg/m2 and 34 kg/m2 and weight at least 50 kg and no more than 120 kg.
- •Additional criteria for renal impaired subjects: - Subjects must have stable renal disease without evidence of renal progressive disease defined as moderate renal impairment (eGFR 30-59 mL/min/1.73m2) or severe renal impairment (eGFR 15-29 mL/min/1.73m2).
- •Additional criteria for matched healthy control subjects: - Matched to at least one renal impaired subject by gender, race, age (± 10 years), and weight (± 20%).
- •An estimated GFR as determined by MDRD equation within normal range as determined by eGFR ≥ 90 mL/min/1.73m2
排除标准
- •Significant illness, including infections, or hospitalization within the 2 weeks prior to dosing, except for the renal impaired subjects who due to their renal disease may be affected by significant medical problems which require frequent hospitalizations.
- •Any surgical or medical condition that may significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study
- •Subject has a medical history of cardiac disease and/or clinically significant ECG abnormalities within 6 months prior to screening.
- •Subject has an active or a history within 6 months prior to screening of clinically significant hematologic, endocrinologic, pulmonary, cardiovascular, hepatic, or allergic disease, medically documented (other than clinical conditions associated with renal impairment for the renal impaired subjects only).
- •- Additional exclusion criteria for renal impaired subjects: - Severe albuminuria > 300 mg/day.
- •Subjects undergoing any method of dialysis.
- •Subjects with renal impairment due to hepatic disease (hepatorenal syndrome).
- •Subjects with clinically significant abnormal findings, not consistent with clinical disease, upon physical examination, ECG or laboratory evaluation.
- •Use of any prescription or non-prescription medication that has the potential to interact with buparlisib within two weeks prior to dosing or during the study.
- •- Additional criteria for matched healthy control subjects: - Use of any prescription or non-prescription medication or vitamins during 14 days prior to dosing.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Moderate renal impairment group
Subjects with moderate renal impairment defined as eGFR of 30-59 mL/min/1.73m2 at screening can be enrolled in this group
干预措施: Buparlisib (Drug)
Severe renal impairment group
Subjects with severe renal impairment defined as eGFR of 15-29 mL/min/1.73m2 at screening can be enrolled in this group
干预措施: Buparlisib (Drug)
Matching healthy control group
Subjects with normal renal function defined as eGFR ≥ 90 mL/min/1.73m2 at screening and matching to the renal impaired subject based on gender, race, age, and weight can be enrolled in this group.
干预措施: Buparlisib (Drug)
结局指标
主要结局
Plasma pharmacokinetic (PK) parameter Cmax
时间窗: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the maximum plasma concentration (PK parameter Cmax). Cmax directly determined from the plasma concentration-time profiles.
Plasma PK parameter AUC0-t
时间窗: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter AU0-t (area under the plasma-concentration time curve from timepoint 0 to time t). AUC determined from the plasma concentration-time profile using non-compartmental analysis.
Plasma PK parameter CL/F
时间窗: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter CL/F (clearance).
Plasma PK parameter AUCinf
时间窗: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter AUCinf (area under the plasma concentration-time curve from time 0 to infinity). AUC determined from the plasma concentration-time profile using non-compartmental analysis.
Urine PK parameter CLR
时间窗: predose, 0-4 h, 4-8 h, 8-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h, 96-120 h, 120-144 h
Measurement of effect of renal impairment on PK of buparlisib by assessment of the urine clearance CLR.
次要结局
- Change from baseline in laboratory parameters(From baseline Day 1 to 30 days post-dose)
- Plasma PK parameter T1/2(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)
- Adverse Events severity and frequency(Baseline Day 1 to 30 days post-dose)
- Unbound plasma PK parameter Vu/F(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)
- Relationship between PK parameters Cmax, AUCinf, AUC0-t, CL/F, urine CLR and renal function.(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)
- Plasma PK parameter Tmax(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)
- Plasma PK parameter Vz/F(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)
- Plasma Protein Binding(predose, 1 hour post-dose)
- Unbound plasma PK parameter Cmax,u(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)
- Unbound plasma PK parameter AUCinf,u(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)
- Unbound plasma PK parameter CLu/F(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)
- Urine PK parameter Ae0-t(predose, 0-4 h, 4-8 h, 8-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h, 96-120 h, 120-144 h)
- Change from baseline in ECG parameters(From baseline Day 1 to 30 days post-dose)
- Unbound plasma PK parameter AUC0-t,u(predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose)