A Phase I Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD5462 Following Single and Multiple Ascending Dose Administration to Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Number of Participants with Adverse Events
研究概览
简要总结
This study will assess the safety, tolerability, and pharmacokinetic (PK) of AZD5462 following single ascending dose (SAD) and multiple ascending dose (MAD) administration in healthy male and female participants and healthy participants of Japanese descent.
详细描述
This Phase I, First in Human (FIH), randomized single-blind, placebo-controlled study will consist of 2 parts (Part A and Part B) with an interleaved study design.
Part A of the study will be a sequential SAD design with 5 dose levels planned to be investigated across 8 cohorts, of which 3 cohorts will solely comprise of participants of Japanese descent. Within each cohort, 6 participants will be randomized to receive AZD5462 and 2 participants randomized to receive placebo.
Part B of the study will be a sequential MAD design with 4 dose levels of AZD5462 planned to be investigated across 5 cohorts, of which 1 cohort will comprise solely of participants of Japanese descent. Within each cohort 6 participants will be randomized to receive AZD5462 and 2 participants randomized to receive placebo.
The duration for participants randomized to Part A of the study is 5 to 6 weeks, and for Part B, 6 to 7 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This study is single blind with regard to treatment (AZD5462 or placebo). This means that the Principal Investigator, all clinical staff involved in the clinical study (except for the unblinded Pharmacist), the participants, and the site monitor will remain blinded, unless safety concerns or a regulatory requirement necessitate unblinding.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female (of non-childbearing potential) participants aged 18 to 50 years of age and healthy participants of Japanese descent, 20 to 50 years of age, with suitable veins for cannulation or repeated venipuncture
- •Females must have a negative pregnancy test at the Screening Visit
- •Have a body mass index between 18 and 32 kg/m^2 inclusive and weigh at least 50 kg and no more than 105 kg inclusive
- •For cohorts comprised solely of participants of Japanese descent, a participant will be considered of Japanese descent only if both parents and all grandparents are Japanese
排除标准
- •History of any clinically important 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
- •Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study drug
- •Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results
- •Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody, and Human immunodeficiency virus
- •Abnormal vital signs
- •Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5462
- •Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks or 5 half-lives of the medication, whichever is longer, prior to the first administration of study drug
- •Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days (or 5 half-lives, whichever is the longest) of the first administration of study drug in this study
- •Clinical signs and symptoms consistent with Coronavirus disease 2019, eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening or on admission
研究组 & 干预措施
Cohort A1: AZD5462 Dose 1
Randomized healthy participants will receive Dose 1 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort A2: AZD5462 Dose 2
Randomized healthy participants will receive Dose 2 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort A3: AZD5462 Dose 3
Randomized healthy participants will receive Dose 3 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort A4 Japanese descent: AZD5462 Dose 3
Randomized participants of Japanese descent will receive Dose 3 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort A5: AZD5462 Dose 4
Randomized healthy participants will receive Dose 4 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort A6 Japanese descent: AZD5462 Dose 4
Randomized participants of Japanese descent will receive Dose 4 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort A7: AZD5462 Dose 5
Randomized healthy participants will receive Dose 5 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort A8 Japanese descent: AZD5462 Dose 5
Randomized participants of Japanese descent will receive Dose 5 of AZD5462.
干预措施: AZD5462 (Drug)
Part A: Placebo (Healthy Participants)
Randomized healthy participants will receive Placebo matched to AZD5462.
干预措施: Placebo (Drug)
Part A: Placebo (Japanese descent participants)
Randomized participants of Japanese descent will receive Placebo matched to AZD5462.
干预措施: Placebo (Drug)
Cohort B1: AZD5462 Dose 1
Randomized healthy participants will receive Dose 1 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort B2: AZD5462 Dose 2
Randomized healthy participants will receive Dose 2 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort B3: AZD5462 Dose 3
Randomized healthy participants will receive Dose 3 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort B4: AZD5462 Dose 4
Randomized healthy participants will receive Dose 4 of AZD5462.
干预措施: AZD5462 (Drug)
Cohort B5 Japanese descent: AZD5462 Dose 4
Randomized participants of Japanese descent will receive Dose 4 of AZD5462.
干预措施: AZD5462 (Drug)
Part B: Placebo (Healthy participants)
Randomized healthy participants will receive Placebo matched to AZD5462.
干预措施: Placebo (Drug)
Part B: Placebo (Japanese descent participants)
Randomized participants of Japanese descent will receive Placebo matched to AZD5462.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants with Adverse Events
时间窗: Upto Follow-up (Part A: Day 10 ± 3; Part B: Day 19 ± 3)
Assessment of the safety and tolerability of AZD5462 following administration of single ascending doses (Part A) and multiple ascending doses (Part B).
次要结局
- Maximum observed plasma (peak) drug concentration (Cmax) for AZD5462(Part A: Day 1 (pre-dose and post-dose), and Days 2, 3, and 10 (post-dose); Part B: Days 1 to 19 (pre and post-doses))
- Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for AZD5462(Part A: Day 1 (pre-dose and post-dose), and Days 2, 3, and 10 (post-dose); Part B: Days 1 to 19 (pre and post-doses))
- Area under plasma concentration time curve from zero to infinity (AUCinf) for AZD5462(Part A: Day 1 (pre-dose and post-dose), and Days 2, 3, and 10 (post-dose); Part B: Days 1 to 19 (pre and post-doses))
- Renal clearance of drug from plasma (CLR) for AZD5462(Part A: Day 1 (pre-dose and post-dose), and Days 2, 3, and 10 (post-dose); Part B: Days 1 to 19 (pre and post-doses))