A Phase I, Single Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Ascending Inhaled Doses of AZD7594 in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Safety profile in terms of adverse events, ECG, blood pressure, pulse, physical examination, body temperature, haematology, clinical chemistry, urinalysis and spirometry.
研究概览
简要总结
The purpose of this study is to evaluate the safety profile and look at levels of AZD7594 and biomarkers in blood when the drug is administered inhaled to healthy subjects
详细描述
A Phase I, Single Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Ascending Inhaled Doses of AZD7594 in Healthy Male Volunteers
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male volunteers aged 18-45 years inclusive with suitable veins for cannulation or repeated vein puncture
- •Have a body mass index (BMI) between 18 and 30 kg/m2 and weight between 50 and 100 kg (inclusive)
- •Be able to inhale from the Spira nebuliser used in the study
- •Be willing to use a condom with spermicide to prevent pregnancy and drug exposure of a female partner
排除标准
- •History of any clinically significant disease or disorder
- •Current smokers
- •Any clinically relevant abnormal findings
研究组 & 干预措施
1
Subjects will participate in 1 of up to 9 groups in Part A (single ascending dose part) or 1 of 4 groups in Part B (multiple ascending dose part). Ratio of subjects receiving AZD7594 versus placebo is 6:2 in part A and 6:3 in Part B.
干预措施: AZD7594 (Drug)
2
Subjects will participate in 1 of up to 9 groups in Part A or 1 of 4 groups in Part B. Ratio of subjects receiving AZD7594 versus placebo is 6:2 in part A and 6:3 in Part B.
干预措施: Placebo to match (Drug)
结局指标
主要结局
Safety profile in terms of adverse events, ECG, blood pressure, pulse, physical examination, body temperature, haematology, clinical chemistry, urinalysis and spirometry.
时间窗: Screening to 13 days post last dose.
No statistical tests will be performed
次要结局
- Single dose pharmacokinetics (PK) of AZD7594 in terms of : Cmax, tmax, λz, t1/2λz, AUC(0-last), AUC(0-24), AUC, CL/F, Vz/F, MRT, Cmax/D, AUC/D, AUC(0-24)/D.(pre-dose and at 5, 15 and 30 minutes and 1, 2, 4, 6, 9, 12, 18, 24, 36 and 48 hours post-dose. From cohort four 72 and 96 hours post-dose samples will also be taken.)
- Multiple dose PK of AZD7594 in terms of: Cmax, tmax, λz, t1λz, AUC(0-last), AUC(0-24), AUC, CL/F, Vz/F, MRT, Cmax/D, AUC/D,AUC(0-24)/D, Cavg, %Fluctuation, Rac(Cmax) and Rac(AUC(0-24) and time-dependency (AUC(0-24) and AUC)(pre-dose and at 5, 15 and 30 min and 1, 2, 4, 6, 9, 12, 18, 24, 48, 72 hours and 96 h post-dose. Days 6-15: Pre-dose samples only.From day 16: pre-dose and 5, 15 and 30 min and 1, 2, 4, 6, 9, 12, 18, 24, 36 and 48 h post-dose.)
- Pharmacodynamics of AZD7594 following a single dose in terms of: 24-hour plasma cortisol(screening and on the dosing day at the following time points 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24. On the dosing day also at 36 and 48 hours post dose.)
- Pharmacodynamics of AZD7594 following a multiple doses in terms of: 24-hour plasma cortisol(screening and days 1 and 16 at the following time points 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 hours. On day 1 also at 36 and 48 hours.)
- Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma cortisol after adrenocorticotropic hormone stimulation(screening and day 17 at 30 minutes and 1 hour post tetracosactide injection)
- Pharmacodynamics of AZD7594 following multiple doses in terms of: Plasma dehydroepiandrosterone sulphate, plasma 4β-OH-cholesterol, and plasma osteocalcin(screening and day 17)