An Open-Label, Two-Cohort Study of Absorption, Distribution, Metabolism, Excretion (ADME) of [14C]AZD4144 Following a Single Oral and IV Dose to Healthy Male Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- 80% or more of the radioactivity recovered in excreta
研究概览
简要总结
This study in healthy volunteers aims to explore blood levels and side effects of the test medicine, and look at how it is broken down when injected into a vein or given as a liquid by mouth. The test medicine will be radiolabeled with a small amount of carbon-14 so it can be tracked in the body.
This study will take place at one site in Nottingham, United Kingdom, and will enroll 2 groups of 8 healthy men aged 30-65 years.
详细描述
This study in healthy volunteers aims to explore blood levels and side effects of the test medicine, and look at how it is broken down when injected into a vein or given as a liquid by mouth. The test medicine will be radiolabelled with a small amount of carbon-14 so it can be tracked in the body.
This study will take place at one site in Nottingham, United Kingdom.
It is planned to enroll 2 groups of 8 healthy men aged 30-65 years.
Each group will take part in 1 treatment period and receive a single dose of radiolabelled test medicine, either by injection into a vein or as a liquid by mouth. They'll stay in the clinic for up to 10 nights, attend 2 outpatient visits, and take up to 7 weeks to finish the study.
Blood and urine samples will be collected to do safety tests. Blood, urine and faecal samples will be collected to measure the amount of test medicine and its breakdown products.
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
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males aged 30 to 65 years inclusive
- •BMI of 18.0 to 32.0 kg/m2 inclusive
- •Regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)
排除标准
- •History of any clinically important disease or disorder
- •History or presence of clinically significant cardiovascular, renal, respiratory, gastrointestinal disease, or neurological or psychiatric disorder
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first dosing day
- •Acute diarrhoea or constipation within 7 days of the first dosing day
- •Participants who do not have suitable veins for multiple venepunctures/cannulation
- •Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis
- •Any clinically significant abnormal findings in vital signs
- •Any clinically significant abnormalities on 12-lead ECG
- •Evidence of renal impairment
- •Participants who have received any IMP in the last 90 days prior to the first dosing day
- •Participants who have previously received AZD4144
- •Radiation exposure exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years, occupationally exposed worker, or have been administered IMP in a radiolabelled ADME study in the last 12 months.
- •Blood or plasma donation, or loss of more than 400 mL blood during the 3 months prior to the study.
- •Use of any prescribed or non-prescribed medication including antacids, gastric pH modifying agents, analgesics, herbal remedies, vitamins and minerals within 2 weeks of the first dosing day
- •Use of drugs or herbal medications with CYP3A4 enzyme-inducing properties such as St John's Wort or CYP3A4 inhibiting properties within 3 weeks of the first dosing day
- •Current smokers or known or suspected history of alcohol or drug abuse
- •Excessive intake of caffeine-containing drinks or food
研究组 & 干预措施
Regimen A
Participants in Cohort 1 will receive a single intravenous injection of [14C]AZD4144 Solution for Infusion
干预措施: [14C]AZD4144 Solution for Infusion (Drug)
Regimen B
Participants in Cohort 2 will receive a single oral dose of [14C]AZD4144 Oral Solution
干预措施: [14C]AZD4144 Oral Solution (Drug)
结局指标
主要结局
80% or more of the radioactivity recovered in excreta
时间窗: Plasma, urine and faecal samples from pre-dose until up to 216 hours post-dose
Identification of greater than 80% of the radioactivity recovered in the urine and/or faeces
Amount of AZD4144 excreted (Ae)
时间窗: Urine and faecal samples collected from pre-dose until up to 216 hours post-dose
Mass balance recovery, rates and routes of elimination of total radioactivity of \[14C\]AZD4144 in urine, faecal and all excreta
Amount of AZD4144 excreted expressed as a percentage of the radioactive dose administered (Fe)
时间窗: Urine and faecal samples collected from pre-dose until up to 216 hours post-dose
Mass balance recovery, rates and routes of elimination of total radioactivity of \[14C\]AZD4144 in urine, faeces and all excreta
Cumulative amount of AZD4144 excreted (CumAe)
时间窗: Urine and faecal samples collected from pre-dose until up to 216 hours post-dose
Mass balance recovery, rates and routes of elimination of total radioactivity of \[14C\]AZD4144 in urine, faecal and all excreta
Cumulative amount of AZD4144 excreted expressed as a percentage of the radioactive dose administered (CumFe)
时间窗: Urine and faecal samples collected from pre-dose until up to 216 hours post-dose
Mass balance recovery, rates and routes of elimination of total radioactivity of \[14C\]AZD4144 in urine, faecal and all excreta
Area under the curve (AUC) of circulating plasma total radioactivity (TR) accounting for 10% or more of the dose
时间窗: Plasma, urine and faecal samples from pre-dose until up to 216 hours post-dose
Identification of the chemical structure of each metabolite accounting for more than 10% by AUC of circulating total radioactivity
次要结局
- Time of maximum observed concentration (tmax) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Maximum observed concentration (Cmax) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Area under the curve from time 0 to the time of last measurable concentration (AUC0-t) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Area under the curve from time of the last measurable concentration to infinity as a percentage of the area under the curve extrapolated to infinity (AUCextrap) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Terminal elimination half-life (T1/2) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Apparent volume of distribution at steady state after a single IV administration (Vss) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Total body clearance calculated after a single IV administration (CL) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Renal clearance calculated using plasma AUC (CLR) for AZD4144 and total radioactivity(Plasma, urine and whole blood samples collected from pre-dose until up to 168 hours post-dose)
- Whole blood:plasma concentration ratios(Whole blood and plasma samples collected from pre-dose until 168 hours post-dose)
- Absolute bioavailability(Plasma samples collected from pre-dose until 168 hours post-dose)