Evaluation of the Pharmacokinetics and Safety of Venetoclax in Subjects With Impaired Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Time to Cmax (Tmax) of Venetoclax (Groups 1,2)
研究概览
简要总结
Renal insufficiency is common in participants with blood cancers. The main objective of this study is to evaluate adverse events and movement of oral venetoclax tablets through the body of female participants with severe normal renal function and those with end stage renal disease (ESRD) requiring hemodialysis.
Venetoclax is an investigational drug being developed for the treatment of various hematologic malignancies. Study doctors put the participants in 1 of 2 groups, called treatment arms. Each group receives a different treatment. Approximately 12 female participants between 18 and 75 years, with Body Mass Index (BMI) between 18 to 42 kg/m2 will be enrolled in approximately 4 sites across the world.
Participants with normal renal function will receive single dose of oral venetoclax tablet. Participants with ESRD will receive oral venetoclax tablets just prior to hemodialysis (Period 1 Day 1) and between dialysis days (Period 2 Day 1), doses in the two periods will be separated by at least 7 days.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood and urine tests, checking for side effects.
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
- Female
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) between 18.0 and 42.0 kg/m
- •Postmenopausal or permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
- •Women of childbearing potential, practicing at least 2 protocol specified methods of birth control that are effective from at least 30 days before starting study drug through at least 30 days after the last dose of any study drug.
- •Group 1 only: Must be in general good health based upon the results of a medical history, physical examination, and 12-lead electrocardiogram (ECG) with normal Glomerular Filtration Rate (GFR) at Screening.
- •Group 2 only: Stable condition and acceptable for study participation based upon the results of a medical history, physical examination, laboratory profile, and ECG. Participant with end stage renal disease (ESRD) requiring dialysis on hemodialysis must have been receiving hemodialysis for at least 1 month.
排除标准
- •Participants on a strict vegetarian or vegan diet.
研究组 & 干预措施
Group 1: Participants With Normal Renal Function
Participants with normal renal function will receive single dose of venetoclax on Day 1.
干预措施: Venetoclax (Drug)
Group 2: Participants With End Stage Renal Disease
Participants with end stage renal disease (ESRD) will receive single dose of venetoclax on Period 1 Day 1 and Period 2 Day 1 (Each period is 3 days separated by 7-day washout period).
干预措施: Venetoclax (Drug)
结局指标
主要结局
Time to Cmax (Tmax) of Venetoclax (Groups 1,2)
时间窗: Up to Day 6
Time to Cmax (Tmax) of Venetoclax.
Unbound Fraction Post-dialysis (fu,postdialysis) of Venetoclax in Plasma (Group 2)
时间窗: Day 1
Unbound fraction post-dialysis (fu,postdialysis) of venetoclax in plasma is calculated in participants undergoing hemodialysis in Period 1.
Percentage of Participants With Adverse Events (AEs)
时间窗: Up to approximately 38 days
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Maximum Plasma Concentration (Cmax) of Venetoclax (Groups 1,2)
时间窗: Up to Day 6
Maximum Plasma Concentration (Cmax) of Venetoclax.
Area Under the Plasma Concentration-time Curve over time from time 0 to 48 hours (AUC0-48) of Venetoclax (Groups 1,2)
时间窗: Up to Day 6
Area Under the Plasma Concentration-time Curve over time from time 0 to 48 hours (AUC0-48).
Pre-dose Unbound Fraction (fu) of Venetoclax in Plasma (Groups 1,2)
时间窗: Day 1
Unbound Fraction (fu) of Venetoclax in Plasma.
Dialysis Clearance (CLdialysis) (Group 2)
时间窗: Day 1
Dialysis Clearance (CLdialysis) is calculated in participants undergoing hemodialysis in Period 1.
Unbound Fraction Pre-dialysis (fu,predialysis) of Venetoclax in Plasma (Group 2)
时间窗: Day 1
Unbound fraction pre-dialysis (fu,predialysis) of venetoclax in plasma is calculated in participants undergoing hemodialysis in Period 1.
次要结局
未报告次要终点