A Phase I Study to Assess Safety, Tolerability, Pharmacokinetics and Effect of Food on Multiple Rising Oral Doses of BI 1839100 (Single-blind, Randomised, Placebo-controlled, Parallel Group Design) and the Effect of Multiple Doses of BI 1839100 on the Single Dose Pharmacokinetics of Cytochrome P450 Substrate (Midazolam), a P Glycoprotein Substrate (Digoxin) and OATP Substrate (Rosuvastatin) Administered Orally (Open-label, Fixed-sequence) in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- DDI part: Maximum measured concentration of midazolam, digoxin and rosuvastatin when administered without BI 1839100 in plasma (Cmax)
研究概览
简要总结
Effects of multiple rising doses of BI 1839100 on safety, tolerability, pharmacokinetics and the effect of high-fat meal on pharmacokinetics of BI 1839100 will be assessed as well as assessing potential drug-drug interactions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
MRD: single blinded to subject DDI: open-label
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
- •Physically and mentally 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 18.5 to 31.9 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 140 millimetre(s) of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (bpm) (subjects with heart rate values between 45 and 50 bpm may only be enrolled in case they have a normal thyroid function, no clinical symptoms associated with the bradycardia and no apparent signs of other diseases causing bradycardia such as hypothyroidism or heart conduction abnormalities)
- •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 assessed as clinically relevant by the investigator
- •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 assessed as clinically relevant by the investigator
- •History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply.
研究组 & 干预措施
MRD part: BI 1839100 dose group 1
Multiple rising dose (MRD)
干预措施: BI 1839100 (Drug)
MRD part: BI 1839100 dose group 2
Multiple rising dose (MRD)
干预措施: BI 1839100 (Drug)
MRD part: BI 1839100 dose group 3
Multiple rising dose (MRD)
干预措施: BI 1839100 (Drug)
MRD part: BI 1839100 dose group 4
Multiple rising dose (MRD)
干预措施: BI 1839100 (Drug)
DDI part
Drug-Drug Interaction (DDI)
干预措施: rosuvastatin (Drug)
MRD part: BI 1839100 dose group 5
Multiple rising dose (MRD)
干预措施: BI 1839100 (Drug)
MRD part: Placebo matching BI 1839100
干预措施: Placebo matching BI 1839100 (Drug)
DDI part
Drug-Drug Interaction (DDI)
干预措施: BI 1839100 (Drug)
DDI part
Drug-Drug Interaction (DDI)
干预措施: midazolam (Drug)
DDI part
Drug-Drug Interaction (DDI)
干预措施: digoxin (Drug)
结局指标
主要结局
DDI part: Maximum measured concentration of midazolam, digoxin and rosuvastatin when administered without BI 1839100 in plasma (Cmax)
时间窗: up to 20 days
MRD part: Occurrence of any treatment-emergent adverse event assessed as drug-related by the investigator
时间窗: up to 26 days
Multiple-rising dose (MRD)
DDI part: Area under the concentration-time curve of midazolam, digoxin and rosuvastatin when co-administered with BI 1839100 over the time interval from 0 to the last quantifiable data point (AUC0-tz)
时间窗: up to 7 days
DDI part: Area under the concentration-time curve of midazolam, digoxin and rosuvastatin when administered without BI 1839100 over the time interval from 0 to the last quantifiable data point (AUC0-tz)
时间窗: up to 20 days
Drug-Drug Interaction (DDI)
DDI part: Maximum measured concentration of midazolam, digoxin and rosuvastatin when co-administered with BI 1839100 in plasma (Cmax)
时间窗: up to 7 days
次要结局
- MRD part: Time from dosing to maximum measured concentration of the analyte in plasma (tmax)(at Day 1)
- MRD part: Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 12 hours (AUC0-12)(at Day 1)
- MRD part: Area under the concentration-time curve of the analyte in plasma over a uniform 12 hours dosing interval (τ) [after Nth dose] (AUCτ( ,N))(up to 17 days)
- MRD part: Maximum measured concentration of the analyte in plasma after single dose (Cmax)(at Day 1)
- MRD part: Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 48 hours (AUC0-48)(up to 48 hours)
- MRD part: Maximum measured concentration of the analyte in plasma [after Nth dose] (Cmax( ,N))(up to 17 days)