Pharmacokinetics, Safety and Tolerability of BI 425809 (Iclepertin) Following Oral Administration in Male and Female Participants With Different Degrees of Hepatic Impairment (Child-Pugh Classification A and B) Compared With Matched Male and Female Participants With Normal Hepatic Function (an Open-label, Non-randomised, Single-dose, Parallel, Individualmatched Design Trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Area under the concentration-time curve of iclepertin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)
研究概览
简要总结
This study is open to people with and without liver problems. People can join the study if they are 18 to 79 years of age and have a body mass index (BMI) between 18.5 and 35 kg/m2.
Iclepertin (also called BI 425809) is a medicine that is being developed to treat diseases of the brain. The purpose of this study is to find out whether having liver problems influences how iclepertin is taken up in the body. All participants take iclepertin once as a tablet.
Participants are in the study for 2 to 3 weeks. During the first part of the study, they stay at the study site for 4 nights. Afterwards, there are 5 visits to the study site and 1 call. The site staff measures the amount of iclepertin in the blood. The doctors also regularly check participants' health and take note of any unwanted 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
- Treatment
- 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
- •Inclusion criteria applicable to all participants:
- •Male or female participants
- •Age 18-79 years (inclusive)
- •Body Mass Index (BMI) of 18.5 to 35 kilograms per meter squared (kg/m2) (inclusive)
- •Signed and dated written informed consent in accordance with International Council for Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
- •Male participants are not required to use contraception
- •Women of childbearing potential are allowed to participate provided they use a highly effective contraception from at least 30 days before the administration of trial medication until 30 days after trial completion.
- •The following methods of contraception are considered adequate for female participants of childbearing potential:
- •Use of combined (oestrogen and progestogen containing) hormonal contraception that prevents ovulation (oral, intravaginal or transdermal), plus condom
- •Use of progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants), plus condom
- •Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- •Sexually abstinent (true abstinence, in line with the preferred and usual lifestyle of the subject) - -A vasectomised sexual partner who received medical assessment of the surgical success (documented absence of sperm) and provided that partner is the sole sexual partner of the trial participant.
- •Female participants are not considered to be of childbearing potential if they are either surgically sterilized (including hysterectomy) or postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of follicle-stimulating hormone (FSH) above 40 unit per liter (U/L) and oestradiol below 30 nanogram per liter (ng/L) is confirmatory).
- •Inclusion criteria applying only to participants with impaired hepatic function:
- •Hepatic impairment classified as Child-Pugh A (score 5-6 points) or Child Pugh B (score 7-9 points)
- •further inclusion criteria apply
- •Inclusion criteria applying only to participants with normal hepatic function:
- •Individually matched to participants with hepatic impairment according to sex, age, and weight
- •further inclusion criteria apply
排除标准
- •Exclusion criteria applying to all participants:
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- •For diabetics only: uncontrolled diabetes mellitus with a glycated hemoglobin (HbA1c) > 9
- •Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics (PK) of the trial medication (except appendectomy or simple hernia repair)
- •Diseases of the Central Nervous System (CNS) (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders (including but not limited to major depressive disorder or history of suicide attempts)
- •History of relevant orthostatic hypotension, fainting spells, or blackouts
- •Relevant chronic or acute infections
- •further exclusion criteria apply
- •Exclusion criteria applying only to participants with hepatic impairment:
- •A marked prolongation of the time from the start of the Q wave to the end of the T wave (QT)/ Corrected QT (QTc) interval (such as QTc Fridericia (QTcF) intervals that are repeatedly greater than 480 milliseconds (ms) in males or repeatedly greater than 500 ms in females) or any other clinically relevant electrocardiogram (ECG) finding at screening
- •further exclusion criteria apply
- •Exclusion criteria applying only to participants with normal hepatic function:
- •Any finding in the medical examination (including blood pressure (BP), pulse rate (PR) or ECG) deviating from normal and assessed as clinically relevant by the investigator
- •further exclusion criteria apply
研究组 & 干预措施
Iclepertin - Control - normal hepatic function
Participants with normal hepatic function were individual-matched (matching criteria: gender, age within ± 10 years, and weight within ± 15%) to participants with mild or moderate hepatic function (Child-Pugh A or B) and received a single dose of 10 milligram iclepertin as a film-coated tablet following an overnight fast of at least 10 hours. Each control participant with normal hepatic function could be matched to 1 participant in 1 or both groups of participants with hepatic impairment.
干预措施: Iclepertin (Drug)
Iclepertin - Child-Pugh A - Mild hepatic impairment
Participants with mild hepatic function (Child-Pugh A) received a single dose of 10 milligram iclepertin as a film-coated tablet following an overnight fast of at least 10 hours.
干预措施: Iclepertin (Drug)
Iclepertin - Child-Pugh B - Moderate hepatic impairment
Participants with Moderate hepatic function (Child-Pugh B) received a single dose of 10 milligram iclepertin as a film-coated tablet following an overnight fast of at least 10 hours.
干预措施: Iclepertin (Drug)
结局指标
主要结局
Area under the concentration-time curve of iclepertin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)
时间窗: Up to 9 days
Maximum measured concentration of iclepertin in plasma (Cmax)
时间窗: Up to 9 days
Area Under the Concentration-time Curve of Iclepertin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
时间窗: Within 2 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144 and 192 hours following drug administration.
Area under the concentration-time curve of iclepertin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale including the fixed effect 'degree of hepatic impairment' and the random effect 'matched pair'.
Maximum Measured Concentration of Iclepertin in Plasma (Cmax)
时间窗: Within 2 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144 and 192 hours following drug administration.
Maximum measured concentration of iclepertin in plasma (Cmax). Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale including the fixed effect 'degree of hepatic impairment' and the random effect 'matched pair'.
次要结局
- Area under the concentration-time curve of iclepertin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)(Up to 9 days)
- Area Under the Concentration-time Curve of Iclepertin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)(Within 2 hours before and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, 144 and 192 hours following drug administration.)