An Open-label Non-randomized, Phase 1 Single Dose Study to Evaluate the Pharmacokinetics and Safety of Copanlisib in Subjects With Impaired Hepatic or Renal Function in Comparison to Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Maximum Observed Concentration (Cmax) of Copanlisib in Plasma.
研究概览
简要总结
To evaluate the pharmacokinetics and safety of copanlisib in subjects with impaired hepatic or renal function in comparison to healthy subjects
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All subjects - Male and female subjects between 18 and 80 years of age with a body mass index above 18.0 and below 34.0 kg / m² and a body weight of above or equal 50 kg.
- •Healthy subjects
- •Healthy subjects as determined by absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms, and clinical laboratory determinations. eGFR ≥ 90 mL/min/1.73 m² (according to Modification of Diet in Renal Disease [MDRD] formula).
- •Subjects with moderate or severe hepatic impairment
- •Subjects with confirmed liver cirrhosis by at least one of the following Criteria: histologically by prior liver biopsy showing cirrhosis, liver imaging (computer tomography, and/or ultrasound and/or magnetic resonance imaging scans, and/or fibroscan), or laparoscopy.
- •Child-Pugh Clinical Assessment Score 7 to 9 (moderate) or Score 10 to 15 (severe).
- •Subjects with severe renal impairment
- •Subjects with severe renal impairment with an estimated glomerular filtration rate 15-29 mL/min/1.73 m² according to MDRD formula.
- •Subjects with stable renal disease: no significant change in renal function as evidenced by serum creatinine value within ±25% from the last determination, obtained within at least 3 months before study entry and the absence of the need to start dialysis in the next 3 months.
排除标准
- •All subjects
- •Active coronary artery disease or myocardial infarction within 6 months of study entry. Immuno-compromised subjects including known history/seropositivity of human immunodeficiency virus (HIV).
- •Other concurrent severe and/or uncontrolled medical conditions (e.g. current diagnosis of type 1 or type 2 diabetes mellitus and with HbA1c >8.5%) that could cause unacceptable safety risks or compromise compliance with protocol.
- •Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder cancer as well as localized prostate cancer.
- •Uncontrolled hypertension despite optimal medical management (per investigator's assessment).
- •Administration of strong CYP3A4 inhibitors or inducers within 2 weeks prior to dosing and during study conduct. (A list of these medications can be found in Section 16.6 of the protocol. However, this list may not be comprehensive).
- •Subjects with moderate or severe hepatic impairment
- •Symptoms or history of encephalopathy (Grade III or worse)
- •Failure of any other major organ other than the liver; severe infection, or any clinically significant illness within 4 weeks prior to study drug administration
- •Renal failure with an eGFR <35 mL/min/1.73 m² Subjects with severe renal impairment
- •Acute renal failure at study entry
- •Nephrotic syndrome
- •Failure of any other major organ other than the kidney
- •Acute hepatorenal syndrome
研究组 & 干预措施
BAY80-6946/Healthy subject
Healthy subjects
干预措施: Copanlisib (ALIQOPA, BAY80-6946) (Drug)
BAY80-6946/moderate hepatically impaired patients
Patients with Child-Pugh B (score 7-9) at the screening visit
干预措施: Copanlisib (ALIQOPA, BAY80-6946) (Drug)
BAY80-6946/severe renal impaired patients
Patients with eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation
干预措施: Copanlisib (ALIQOPA, BAY80-6946) (Drug)
BAY80-6946/severe hepatically impaired patients
Patients with Child-Pugh C (score 10-15) at the screening visit
干预措施: Copanlisib (ALIQOPA, BAY80-6946) (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of Copanlisib in Plasma.
时间窗: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Area Under the Concentration vs. Time Curve From Zero to Infinity (AUC) of Copanlisib in Plasma.
时间窗: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion
AUC refers to area under the concentration vs time curve from 0 to infinity which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Area Under the Concentration-time Curve of Copanlisib in Plasma Over the Time Interval From 0 to 168 h.
时间窗: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion
AUC(0-168) refers to AUC from time 0 to 168 hr which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
次要结局
- Number of Subjects With Treatment-emergent Adverse Events (TEAEs) in Different Severity.(Up to 30 days after end of treatment with study drug)
- Number of Subjects With Treatment-emergent Adverse Events (TEAEs)(Up to 30 days after end of treatment with study drug)
- Maximum Observed Concentration (Cmax) of Metabolite M-1.(before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion)
- Area Under the Concentration-time Curve of Metabolite M-1 in Plasma Over the Time Interval From 0 to 168 h.(before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion)