Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 474121 in Young and Elderly Healthy Male and Female Subjects (Double-blind, Randomised, Placebo-controlled, Parallel Group Design) and Evaluation of Midazolam Interaction in Young Healthy Male and Female Subjects (Nested, Open, Fixed-sequence, Intra-individual Comparison)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Drug-related Adverse Events
研究概览
简要总结
The main objectives of this trial are to investigate safety and tolerability of BI 474121 in healthy male and female young and elderly subjects following oral administration of multiple rising doses per day over 14 days.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
- •Age of 18 to 45 years (inclusive) for young or 65 to 80 years (inclusive) for elderly healthy volunteers
- •BMI of 18.5 to 29.9 kg/m2 (inclusive)
- •Signed and dated written informed consent prior to admission to the study, in accordance with GCP and local legislation
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 100 to 140 mm Hg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 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
- •A positive Poly-chain reaction (PCR) test for SARS-CoV-2 and clinical symptoms suggestive for this disease at screening or on Day -3
- •Further exclusion criteria apply
研究组 & 干预措施
BI 474121 2.5mg (Part A)
Young participants administered 1 tablet of 2.5 milligrams (mg) BI 474121 orally once daily over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily.
干预措施: BI 474121 (Drug)
BI 474121 2.5mg (Part A)
Young participants administered 1 tablet of 2.5 milligrams (mg) BI 474121 orally once daily over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily.
干预措施: Midazolam (Drug)
BI 474121 5mg (Part A)
Young participants administered 2 tablets of 2.5 mg BI 474121 orally once daily (daily dose: 5 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
干预措施: BI 474121 (Drug)
BI 474121 10mg (Part A)
Young participants administered 1 tablet of 10 milligrams (mg) BI 474121 orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).
干预措施: BI 474121 (Drug)
BI 474121 10mg (Part A)
Young participants administered 1 tablet of 10 milligrams (mg) BI 474121 orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).
干预措施: Midazolam (Drug)
BI 474121 20mg (Part A)
Young participants administered 2 tablets of 10 milligrams (mg) BI 474121 orally once daily (daily dose: 20 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).
干预措施: BI 474121 (Drug)
BI 474121 20mg (Part A)
Young participants administered 2 tablets of 10 milligrams (mg) BI 474121 orally once daily (daily dose: 20 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).
干预措施: Midazolam (Drug)
BI 474121 30mg (Part A)
Young participants administered 3 tablets of 10 milligrams (mg) BI 474121 orally once daily (daily dose: 30 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).
干预措施: BI 474121 (Drug)
BI 474121 30mg (Part A)
Young participants administered 3 tablets of 10 milligrams (mg) BI 474121 orally once daily (daily dose: 30 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h).
干预措施: Midazolam (Drug)
Placebo (Part A)
Young participants administered matching placebo to part A once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) for placebo participants matched to 2.5mg BI, 10mg BI, 20mg BI, and 30mg BI groups.
干预措施: BI 474121 (Drug)
Placebo (Part A)
Young participants administered matching placebo to part A once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) for placebo participants matched to 2.5mg BI, 10mg BI, 20mg BI, and 30mg BI groups.
干预措施: Midazolam (Drug)
Placebo (Part A)
Young participants administered matching placebo to part A once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
On Day -1, 1, and 14, 75 micrograms (μg) of midazolam for injection used as oral solution were administered orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) for placebo participants matched to 2.5mg BI, 10mg BI, 20mg BI, and 30mg BI groups.
干预措施: Placebo (Drug)
Placebo (Part B)
Elderly participants administered matching placebo to part B once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days
干预措施: Placebo (Drug)
BI 474121 5mg (Part B)
Elderly participants administered 2 tablets of 2.5 mg BI 474121 orally once daily (daily dose: 5 mg) with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
干预措施: BI 474121 (Drug)
BI 474121 10mg (Part B)
Elderly participants administered 1 tablet of 10 milligrams (mg) BI 474121 orally once daily with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) over a treatment period of 14 days.
干预措施: BI 474121 (Drug)
结局指标
主要结局
Percentage of Participants With Drug-related Adverse Events
时间窗: For Midazolam: From first dose of midazolam (on Day -1) until first dose of BI 474121/Placebo, up to 1 day. Other groups: From first dose of BI 474121/Placebo until last dose+7 days of residual effect period, up to 21 days.
Percentage of participants with drug-related adverse events is reported. Medical judgment were used to determine the relationship between study medication and the adverse events, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.
次要结局
- Maximum Measured Concentration of BI 474121 in Plasma (Cmax) After First Dose(Within 1 hour (h) before and at 15 minutes (min), 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h45min after first dose of BI 474121.)
- Maximum Measured Concentration of BI 474121 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)(Within 15 minutes (min) before and at 15 min, 30min, 1hour (h), 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h after administration of BI 474121 on Day 14.)
- Maximum Measured Concentration of Midazolam in Plasma (Cmax) - Day -1(Within 1 hour (h) 30 minutes (min) before and at 15min, 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h after the administration of Midazolam on Day -1.)
- Maximum Measured Concentration of Midazolam in Plasma (Cmax) - Day 1(Within 1 hour (h) before and at 15 minutes (min), 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h45min after administration of Midazolam on Day 1.)
- Area Under the Concentration-time Curve of BI 474121 in Plasma From 0 to 24h (AUC0-24) After First Dose(Within 1 hour (h) before and at 15 minutes (min), 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h45min after first dose of BI 474121.)
- Area Under the Concentration-time Curve of BI 474121 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)(Within 15 minutes (min) before and at 15 min, 30min, 1hour (h), 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h after administration of BI 474121 on Day 14.)
- Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) - Day 1(Within 1 hour (h) before and at 15 minutes (min), 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h45min after administration of Midazolam on Day 1.)
- Maximum Measured Concentration of Midazolam in Plasma (Cmax) - Day 14(Within 15 minutes (min) before and at 15min, 30min, 1hour (h), 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h after administration of Midazolam on Day 14.)
- Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) - Day -1(Within 1 hour (h) 30 minutes (min) before and at 15min, 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 23h after the administration of Midazolam on Day -1.)
- Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) - Day 14(Within 15 minutes (min) before and at 15min, 30min, 1hour (h), 1h30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h after administration of Midazolam on Day 14.)