A Phase I Randomized, Single-blind, Placebo-controlled, and Sequential Group Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4144 Following Single and Multiple Ascending Doses Via Intravenous Administration, and an Open-label, 2-Period, 2-Sequence, Cross-over Study to Assess the Effects of Intravenous AZD4144 on Rosuvastatin and Furosemide Pharmacokinetics in Healthy Participants

AstraZeneca1 个研究点分布在 1 个国家目标入组 91 人开始时间: 2024年7月15日最近更新: 2025年7月4日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: AstraZeneca
入组人数: 91
试验地点: 1
主要终点: Number of participants with adverse events (AEs) (Part A and Part B)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study consists of 3 parts: Part A, Part B and Part C. This study will compare the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD4144 with placebo in healthy participants, in Part A and Part B. Part C of this study will investigate the possibility of drug-drug interaction (DDI) between IV AZD4144 and oral rosuvastatin and furosemide by evaluating the PK of rosuvastatin and furosemide when administered alone and in combination with single IV dose of AZD4144

详细描述

This is a Phase I, randomized study in healthy participants and consists of 3 parts; Part A, Part B and Part C. Part A and B are single-blind, placebo-controlled with single ascending dose (SAD) and multiple ascending dose (MAD) sequential group design, respectively. Part C is an open-label, 2-period, 2-sequence, cross-over design study. Part A and B of the study will assess the safety, tolerability, PK, and PD of AZD4144 solution for infusion compared with placebo while Part C will investigate the possibility of DDI between IV AZD4144 and oral rosuvastatin and furosemide by evaluating the PK of rosuvastatin and furosemide when administered alone and in combination with single IV dose of AZD4144

The study will comprise of:

A screening period of maximum 28 days.
A residential period which lasts from,
Day -1 to Day 4 (single dose on Day 1) for Part A
Day -1 to Day 15 (dosed on days 1, 4-12) for Part B
Day -1 to Day 3 (dose on Day 1) and Day 9 to Day 12 (dose on Day 10) for Part C
A final follow-up visit,
On Day 10+3 for Part A
On Day 20+3 for Part B and C

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Sequential
主要目的: Treatment
盲法: Triple (Participant, Care Provider, Investigator)

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

•All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
•Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception.
•Females of non-childbearing potential must be confirmed at the Screening Visit.
•Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
•Have a BMI between 18 and 32 kg/m2 inclusive at both Screening and Admission and weigh at least 45 kg at Screening.
•For healthy Japanese cohorts (Part A2 and Part B2): healthy male and female participants are to be Japanese, defined as having both parents and 4 grandparents who are Japanese. This includes second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.
•For healthy Chinese cohort (Part A3): healthy male and female Chinese participants for whom both parents and all grandparents are Chinese and not lived outside of China for more than 10 years.

排除标准

•History of any clinically important disease or disorder 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.
•Clinically significant serious active and chronic infections.
•Any history or evidence of TB (active or latent).
•Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.
•Bacillus Calmette Guérin vaccine within one year prior to signing the ICF.
•Any abnormal laboratory values at the Screening Visit or on Admission to the Clinical Unit.
•Any positive result on Screening for serum Hepatitis B surface antigen (HBsAg), anti-Hepatitis B core (HBc), hepatitis C antibody, or Human immunodeficiency virus (HIV).
•Any clinically important abnormalities in ECG.
•History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
•Known hypersensitivity to furosemide and rosuvastatin (for Part C only)
•History of alcohol abuse or excessive intake of alcohol or current smokers or those who have smoked or used nicotine products.
•Use of drugs with enzyme inducing properties or of any prescribed or nonprescribed medication or of systemic hormonal contraceptives.
•Clinical signs and symptoms consistent with COVID-19.