A Phase I, Open-label Trial in Two Parallel Parts to Investigate Mass Balance, Metabolism, and Basic Pharmacokinetics of BI 1810631 (C-14) Administered as Oral Solution (Part A) and to Investigate Absolute Bioavailability of BI 1810631 Administered as Film-coated Tablet Together With an Intravenous Microtracer Dose of BI 1810631 (C-14) (Part B) in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Part A - Fraction Excreted in Urine and Faeces as Percentage of the Administered Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe0-tz)
研究概览
简要总结
Part A - the primary objective is to assess the mass balance and total recovery of [14C]-radioactivity in urine and faeces after oral single dose administration of BI 1810631 (C-14) (test treatment T1) in healthy male subjects.
Part A - the secondary objective is to assess concentrations of BI 1810631 and [14C]-radioactivity in plasma.
Part B - the primary objective is to investigate the absolute bioavailability of BI 1810631 administered as film-coated tablet (test treatment T2, not radio-labelled) compared with BI 1810631 (C-14) (reference treatment R) administered as intravenous microtracer.
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 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
- •Age of 18 to 55 years (inclusive)
- •Body mass index (BMI) of 18.0 to 30.0 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
排除标准
- •Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
- •Repeated measurement of systolic blood pressure outside the range of 90 to 145 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 45 to 90 mmHg, or pulse rate outside the range of 40 to 100 beats per minute (bpm)
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
- •Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
- •History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply
研究组 & 干预措施
Part A - zongertinib (C-14) (T1)
Healthy male subjects were administered a single oral dose of radioactively-labelled zongertinib (C-14) as a solution (test treatment 1 [T1]) with 240 milliliter (mL) of water, after an overnight fast of at least 10 hours (h).
The solution contained a mixture of pure [14C]-labelled zongertinib ("hot") drug substance, and zongertinib, i.e. unlabeled ("cold") drug substance, and it contained a radioactive dose of approximately 3.7 Megabecquerel (MBq).
干预措施: zongertinib (C-14) (Drug)
Part B - zongertinib (T2), then zongertinib (C-14) (R)
Healthy male subjects were administered one zongertinib film-coated tablet (test treatment 2 [T2]) orally with 240 mL of water after an overnight fast of at least 10 h.
Two hours later, subjects were administered a single solution of radioactively-labelled zongertinib (C-14) (reference treatment [R]) via intravenous infusion. The solution contained a mixture of pure [14C]-labelled zongertinib ("hot") drug substance and zongertinib, i.e. unlabelled ("cold") drug substance, and contained a radioactive dose of approximately 0.03 MBq.
干预措施: zongertinib (Drug)
Part B - zongertinib (T2), then zongertinib (C-14) (R)
Healthy male subjects were administered one zongertinib film-coated tablet (test treatment 2 [T2]) orally with 240 mL of water after an overnight fast of at least 10 h.
Two hours later, subjects were administered a single solution of radioactively-labelled zongertinib (C-14) (reference treatment [R]) via intravenous infusion. The solution contained a mixture of pure [14C]-labelled zongertinib ("hot") drug substance and zongertinib, i.e. unlabelled ("cold") drug substance, and contained a radioactive dose of approximately 0.03 MBq.
干预措施: zongertinib (C-14) (Drug)
结局指标
主要结局
Part A - Fraction Excreted in Urine and Faeces as Percentage of the Administered Dose Over the Time Interval From 0 to the Last Quantifiable Time Point (fe0-tz)
时间窗: Within 18 h (urine) or 48 h (faeces) before drug intake; at 0-4, 4-8, 8-12, 12-24 (urine); and at 24 h sampling intervals until 336 h after drug intake (both). Both: after 336 h, every 7 days, up to day 42. Continues in description.
Mass balance and total recovery of \[14C\]-radioactivity: fraction excreted in urine and faeces given as percentage of the administered oral dose of zongertinib (assessed by \[14C\]zongertinib-equivalent\[EQ\]) over the time interval from 0 to the last quantifiable time point (feurine, 0-tz; fefaeces, 0-tz) is reported. Timeframe (continued): after 336 h, if warranted, 24 h collections were to be performed every 7 days on days 21, 28, 35, and 42. Sampling was stopped when the release criteria for radioactivity recovery were met (earliest stopping on Day 15).
Part B - Dose-normalised Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞,Norm)
时间窗: Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, [zongertinib], 2, 2.08, 2.16, 2.25, 2.5, 2.75, 3, 3.5 [[14C]zongertinib], 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, and 168 h [zongertinib and [14C]zongertinib] after first drug administration.
The dose-normalised area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞,norm) after oral administration of zongertinib, and after intravenous administration of \[14C\]zongertinib, is reported. 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. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model, which included the effect 'subjects' as a random effect and 'treatment' as a fixed effect. These quantities were then back-transformed to the original scale.
次要结局
- Part A - Maximum Measured Concentration of Zongertinib in Plasma (Cmax)(Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 168, 216, 264, 336 h after drug administration.)
- Part A - Maximum Measured Concentration of [14C]-Radioactivity (Assessed by [14C]Zongertinib-EQ) in Plasma (Cmax)(Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 168, 216, 264, 336 h after drug administration.)
- Part A - Area Under the Concentration-time Curve of Zongertinib in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz)(Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 168, 216, 264, 336 h after drug administration.)
- Part A - Area Under the Concentration-time Curve of [14C]-Radioactivity (Assessed by [14C]Zongertinib-EQ) in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz)(Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 168, 216, 264, 336 h after drug administration.)
- Part B - Dose-normalised Maximum Measured Concentration in Plasma (Cmax,Norm)(Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, [zongertinib], 2, 2.08, 2.16, 2.25, 2.5, 2.75, 3, 3.5 [[14C]zongertinib], 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, and 168 h [zongertinib and [14C]zongertinib] after first drug administration.)
- Part B - Dose-normalised Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to the Last Quantifiable Time Point (AUC0-tz,Norm)(Within 3 h prior and 0.5, 1, 1.5, 2, 2.5, 3, [zongertinib], 2, 2.08, 2.16, 2.25, 2.5, 2.75, 3, 3.5 [[14C]zongertinib], 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, and 168 h [zongertinib and [14C]zongertinib] after first drug administration.)