Investigation of Pharmacokinetics, Safety and Tolerability of Neladenoson Bialanate in Male and Female Subjects With Renal Impairment and in Age-, Gender-, and Weight-matched Healthy Subjects Following a Single Oral Dose of 10 mg Neladenoson Bialanate Given as IR Tablet in a Single-center, Nonrandomized, Non-controlled, Non-blinded, Study With Group Stratification
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Bayer
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Cmax for BAY 84-3174
研究概览
简要总结
Neladenoson bialanate is currently under clinical development for a condition in which the heart has trouble pumping blood through the body (chronic heart failure). Renal impairment which co-occurs in patients with heart failure is a common condition in which the kidneys are not filtering the blood as well as they should. The goal of the study is to learn more about the safety of neladenoson bialanate, how it is tolerated and the way the body absorbs, distributes and excretes the study dug given as a single oral dose of 10 mg immediate release tablet in participants with renal impairment and healthy participants matched for age-, gender-, and weight
详细描述
Study was originally designed with 4 arms (normal renal function, mild, moderate, and severe renal impairment), however as the study was prematurely terminated, there was no participant with normal renal function enrolled
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All subjects:
- •Male or female White subjects (women without childbearing potential), aged 18 to 79 years (inclusive), body mass index 18 to 34 kg/m² (both inclusive)
- •Subjects with renal impairment:
- •Estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m² determined from serum creatinine 2-14 days prior to dosing using the Modification of Diet in Renal Disease equation
- •Stable renal disease, i.e. a serum creatinine value determined at least 3 months before the pre-study visit should not vary by more than 25% from the serum creatinine value determined at the pre-study visit.
- •Healthy subjects:
- •Age-, weight- and gender matched healthy subjects
排除标准
- •An anatomical abnormality of the gut (e.g. gut surgery, continent ileostomy) that could affect the retention times of the drug in the stomach/gut adversely
- •Gastric vagotomy or other condition that might adversely affect the gastric pH level
- •Pancreatic dysfunction/insufficiency
- •Febrile illness within 1 week prior to admission to study center
- •Use of the following co-medications
- •From 2 weeks before administration until end of follow-up:
- •Cytochrome P450 (CYP)3A4 inhibitors (Of note: grapefruit is a strong CYP3A4 inhibitor)
- •CYP3A4 inducers
- •CYP2C8 inhibitors (Of note: clopidogrel is a strong CYP2C8 inhibitor)
- •Theophylline
- •On the day of dosing with neladenoson bialanate:
- •Drugs that undergo significant systemic metabolism over gut wall uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) substrates (e.g. irinotecan)
- •Major breast cancer resistance protein (BCRP) substrates
- •Regular daily consumption of more than 1 L - Plasmapheresis within 4 weeks before study drug administration
- •Therapies (e.g. physiotherapy, acupuncture, etc.) within 1 week before study drug administration
- •History of relevant and not cured cardiac rhythm disorders (i.e. Wolff-Parkinson-White syndrome, intermittent second- or third-degree AV block)
- •Positive urine drug screening
- •Subjects tested to be positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus
研究组 & 干预措施
Neladenoson bialanate, mild renal impairment
Subjects with eGFR ≥60 - <90 mL/min/1.73 received a single immediate-release (IR) tablet dose of 10 mg of neladenoson bialanate in the fasted state
干预措施: Neladenoson bialanate (BAY 1067197) (Drug)
Neladenoson bialanate, moderate renal impairment
Subjects with eGFR ≥30 - <60 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state
干预措施: Neladenoson bialanate (BAY 1067197) (Drug)
Neladenoson bialanate, severe renal impairment
Subjects with eGFR <30 mL/min/1.73 received a single IR tablet dose of 10 mg of neladenoson bialanate in the fasted state
干预措施: Neladenoson bialanate (BAY 1067197) (Drug)
Neladenoson bialanate, control group
Healthy subjects matched for age, gender and body weight received a single IR tablet dose of 10 mg neladenoson bialanate in the fasted state
干预措施: Neladenoson bialanate (BAY 1067197) (Drug)
结局指标
主要结局
Cmax for BAY 84-3174
时间窗: Pre-dose up to approximately 6 weeks after dosing
Maximum observed drug concentration in measured matrix after single dose administration
AUC for BAY 84-3174
时间窗: Pre-dose up to approximately 6 weeks after dosing
Area under the concentration vs. time curve from zero to infinity after single dose administration
Cmax,u for BAY 84-3174
时间窗: Pre-dose up to approximately 6 weeks after dosing
Cmax of unbound drug after single dose administration
fu for BAY 84-3174
时间窗: At 4 hours after dosing
Fraction of free (unbound) drug in plasma or serum after single dose administration
Cmax,norm for BAY 84-3174
时间窗: Pre-dose up to approximately 6 weeks after dosing
Cmax divided by dose per body weight after single dose administration
AUCnorm for BAY 84-3174
时间窗: Pre-dose up to approximately 6 weeks after dosing
AUC divided by dose per body weight after single dose administration
AUCu for BAY 84-3174
时间窗: Pre-dose up to approximately 6 weeks after dosing
AUC of unbound drug after single dose administration
次要结局
- Number of subjects with treatment-emergent adverse events (TEAEs)(Up to approximately 6 weeks after dosing)