Investigation of the Pharmacokinetics, Safety, and Tolerability of Neladenoson Bialanate in Subjects With Hepatic Impairment (Classified as Child Pugh A and B) and in Age-, Weight-, and Gender-matched Healthy Subjects, Following a Single Oral Dose in a Single-center, Non-randomized, Non-controlled, Non-blinded Study
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Bayer
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- AUC 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). Liver impairment is a condition in which the liver is not working 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 neladenoson bialanate in participants with liver impairment and healthy participants matched for age-, gender-, and weight
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 and female Caucasian subjects between 18 and 79 years of age (both inclusive) with a body mass index above/equal 18.0 and below/equal 34.0 kg/m² Subjects with hepatic impairment
- •Subjects with documented liver cirrhosis confirmed by histopathology, e.g., previous liver biopsy, laparoscopy, ultrasound, or fibroscan
- •Subjects with hepatic impairment as per Child Pugh system
- •Subjects with stable liver disease during the last 2 months Healthy subjects
- •Healthy subjects with mean age and body weight not varying by more than ±10 years and ±10 kg from the groups of subjects with mild and moderate hepatic impairment, respectively.
排除标准
- •Medical history of continent ileostomy.
- •Febrile illness within 1 week prior to admission to study center.
- •Known hypersensitivity to the study drug (active substances or excipients of the preparation).
- •Subjects with diagnosed malignancy within the past 5 years.
- •Use of any systemic or topical medicine or substances which oppose the study objectives or which might influence them, in particular:
- •Starting from screening on, but minimum from 2 weeks before the study drug administration until the follow-up visit:
- •CYP3A4 inducers
- •CYP3A4 inhibitors
- •Potent CYP2C8 inhibitors
- •Major uridine diphosphate-glucuronosyltransferase isoenzyme 1A1 (UGT1A1) substrate (irinotecan)
- •On the day of administration of neladenoson bialanate:
- •Major breast cancer resistance protein (BCRP) substrates
- •Regular daily consumption of more than 500 mL of usual beer or the equivalent quantity of of more than 2 units of alcohol in another form - Intake of ethanol containing food and beverages from 48 h prior to admission to the study center until 96 h after study drug administration, afterwards not more than 2 units of alcohol per day until follow-up examination.
- •Intake of food and beverages containing grapefruit or pomelo from 14 days prior to study drug administration up to the last time point of PK sampling.
- •Therapies (e.g. physiotherapy, acupuncture, etc.) within 1 week before study drug administration.
- •Positive urine drug screening.
- •Positive results for human immune deficiency - Abnormal (clinically significant) thyroid stimulating hormone (TSH).
研究组 & 干预措施
Neladenoson bialanate, mild hepatic impairment
Subjects with Child Pugh score 5 or 6 received a single immediate-release (IR) tablet dose of 10 mg neladenoson bialanate in the fasted state
干预措施: Neladenoson bialanate (BAY 1067197) (Drug)
Neladenoson bialanate, moderate hepatic impairment
Subjects with Child Pugh score 7-9 received a single IR tablet dose of 10 mg 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
AUC for BAY 84-3174
时间窗: Pre-dose up to 49 days after study drug administration
Area under the concentration vs. time curve from zero to infinity after single dose administration
AUCu for BAY 84-3174
时间窗: Pre-dose up to 49 days after study drug administration
AUC of unbound drug after single dose administration
fu for BAY 84-3174
时间窗: At 4 hours after study drug administration
Fraction of free (unbound) drug in plasma or serum after single dose administration
AUCnorm for BAY 84-3174
时间窗: Pre-dose up to 49 days after study drug administration
AUC divided by dose per body weight after single dose administration
Cmax for BAY 84-3174
时间窗: Pre-dose up to 49 days after study drug administration
Maximum observed drug concentration in measured matrix after single dose administration
Cmax,u for BAY 84-3174
时间窗: Pre-dose up to 49 days after study drug administration
Cmax of unbound drug after single dose administration
Cmax,norm for BAY 84-3174
时间窗: Pre-dose up to 49 days after study drug administration
Cmax divided by dose per body weight after single dose administration
次要结局
- Number of subjects with treatment-emergent adverse events (TEAEs)(Up to 49 days after study drug administration)