A Fixed Sequence, Open-label Study to Assess the Effect of Multiple Doses of AZD4831 on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam
研究概览
简要总结
The study is an open-label, fixed-sequence, cross-over study conducted at a single Clinical Unit to assess the pharmacokinetics (PK) of midazolam in healthy male and female (non-childbearing potential) subjects when administered alone and in combination with AZD4831 after multiple doses (once daily) of AZD4831 for 10 consecutive days.
详细描述
The study will consist of 2 treatment periods and will comprise:
- A Screening period of maximum 28 days;
- Treatment Period 1 and Treatment Period 2:
Treatment Period 1: Midazolam only (Day 1). Treatment Period 2: AZD4831 only (Days 2 to 10, once daily dosing) and AZD4831 plus midazolam (Day 11).
- A final Follow-up Visit after the last administration of investigational medicinal product (IMP) (Day 20 [± 1 day]).
Each subject will be involved in the study for approximately 7 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and/or female subjects with suitable veins for cannulation or repeated venepuncture.
- •Males must be willing to use appropriate contraception methods.
- •Females must not be lactating and must be of non-childbearing potential, confirmed at Screening.
- •Have a body mass index between 18.5 and 30 kg/m^2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive) at Screening.
排除标准
- •History of any clinically significant disease or disorder.
- •History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •A positive Corona Virus Disease 2019 test at Screening or admission to the Clinical Unit on Day -
- •Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results.
- •Any clinically significant abnormal findings in vital signs.
- •clinically significant abnormalities on 12-lead electrocardiogram.
- •Any positive result at the Screening Visit for Hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody.
- •Known or suspected history of drug abuse in the last 2 years.
- •Current smokers or those who have smoked or used nicotine products within the 3 months prior to the Screening Visit.
- •Known or suspected history of alcohol or drug abuse.
- •Use of any prescribed or non-prescribed medication.
- •Subjects with acute pulmonary insufficiency, marked neuromuscular respiratory weakness, obsessional states, phobic states, sleep apnoea syndrome, or unstable myasthenia gravis.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigatoror history of hypersensitivity to drugs with a similar chemical structure or class to AZD4831 or midazolam.
- •History or ongoing allergy/hypersensitivity to drugs(including but not limited to rash, angioedema, acute urticaria).
- •Subjects who, in the opinion of the Investigator, have any clinically significant skin condition.
研究组 & 干预措施
Treatment Arm
Subjects will receive midazolam on Day 1 and AZD4831 once daily from Days 2 to 10, and AZD4831 plus midazolam on Day 11.
干预措施: AZD4831 (Drug)
Treatment Arm
Subjects will receive midazolam on Day 1 and AZD4831 once daily from Days 2 to 10, and AZD4831 plus midazolam on Day 11.
干预措施: Midazolam (Drug)
结局指标
主要结局
Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam
时间窗: Days 1, 2, 11, and 12
Effect of AZD4831 on AUCinf of Midazolam will be assessed.
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Midazolam
时间窗: Days 1, 2, 11, and 12
Effect of AZD4831 on AUClast of Midazolam will be assessed.
Maximum observed plasma (peak) drug concentration (Cmax) of Midazolam
时间窗: Days 1, 2, 11, and 12
Effect of AZD4831 on Cmax of Midazolam will be assessed.
次要结局
- Time to reach peak or maximum observed concentration or response following drug administration (tmax) of Midazolam and AZD4831(Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12)
- Half life associated with terminal slope (λz) of a semi logarithmic concentration timecurve (t½λz) of Midazolam and AZD4831(Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12)
- Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Midazolam and AZD4831(Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12)
- Apparent volume of distribution based on terminal phase (Vz/F) of Midazolam(Days 1, 2, 11, and 12)
- Area under the plasma concentration-curve across the dosing interval (AUCtau) of AZD4831(Days 2-12)
- Cmax of AZD4831(Days 2-12)
- Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831(Days 3-10)
- Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831(Day 11)
- Number of patients with adverse events (AE) and serious AEs (SAE)(From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20))