A Phase 1 and 2 Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of AZD8233 Following a Multiple Subcutaneous Dose Administration in Japanese Participants With Dyslipidemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 87
- 试验地点
- 8
- 主要终点
- Part B: Change in LDL-C in Serum at Week 12
研究概览
简要总结
A Phase 1 and 2 Study of AZD8233 in Participants with Dyslipidemia and this study consists of Part A , Part B and Part C. Part A is designed as a randomized, single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study. Part B is designed as a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 study. Part C is designed as a randomized , single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study.
详细描述
Part A: This is designed as a randomized, single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study.
Approximately 11 Japanese participants will be randomized in an 8:3 ratio into 1 of the 2 single-blinded treatment arms; AZD8233 high dose or placebo. Participants will be dosed SC on Days 1, 8, 29, and 57.
Part B:This is designed as a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 study. Approximately 60 Japanese participants will be randomized in a 1:1:1 ratio into 1 of the 4 double-blinded treatment arms; AZD8233 low dose, AZD8233 medium dose, or placebo. Participants will be dosed SC on Days 1, 29, and 57.
Part C:This is designed as a randomized, single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study.
Approximately 11 Japanese participants will be randomized in an 8:3 ratio into 1 of the 2 single-blinded treatment arms; AZD8233 medium dose or placebo. Participants will be dosed SC on Days 1, 29, and 57.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Part A: Single blind Part B: Double blind Part C: Single blind
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be 20 to 60 years of age inclusive, at the time of signing the informed consent
- •Participants who have a fasting LDL-C ≥ 70 mg/dL but < 140 mg/dL at screening
- •Participants who have fasting triglycerides < 400 mg/dL at screening
- •Participants who should be receiving statin therapy
- •Participants who should be on stable medication for a certain time period prior to randomization
- •Body mass index (BMI) between 19 and 40 kg/m2
- •Females must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating , and must be of nonchild-bearing potential
- •Participants must be 20 to 75 years of age inclusive, at the time of signing the informed consent
- •Have a fasting LDL-C ≥ 70 mg/dL but < 190 mg/dL at screening (Visit 2)
- •Have fasting triglycerides < 400 mg/dL at screening (Visit 2)
- •Should be receiving statin therapy
- •LDL-lowering medications should be on stable dosing for ≥ 3 months prior to screening with no planned medication or dose change during study participation
- •BMI between 19 and 40 kg/m2
- •Female participants must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating, and must not be of childbearing potential
- •Participants must be 20 to 60 years of age inclusive, at the time of signing the informed consent
- •Participants who have a fasting LDL-C ≥ 70 mg/dL but < 140 mg/dL at screening
- •Participants who have fasting triglycerides < 400 mg/dL at screening
- •Participants who should be receiving statin therapy
- •Participants who should be on stable medication for a certain time period prior to randomization
- •Body mass index (BMI) between 19 and 40 kg/m2
- •Females must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating , and must be of nonchild-bearing potential
排除标准
- •eGFR < 60 mL/min/1.73m2 using the Japanese equation
- •Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding. Or participants receiving anti-coagulation therapy
- •History of major bleed or high-risk of bleeding diathesis
- •Subjects with a high 10-year risk of coronary heart disease as calculated using the Suita score
- •Heart rate after 10 minutes of sitting rest < 50 or > 100 beats per minute
- •Uncontrolled hypertension defined as sitting SBP > 140 mmHg or DBP > 90 mmHg
- •eGFR < 40 mL/min/1.73m2 using the Japanese equation at Visit 1
- •Poorly controlled type 2 diabetes mellitus (T2DM), defined as Haemoglobin A1c (HbA1c) > 10% at Visit 1
- •Acute ischaemic cardiovascular event in the last 12 months prior to randomization
- •Heart failure with New York Heart Association (NYHA) Class III-IV
- •High-risk of bleeding diathesis as judged by the Investigator
- •Uncontrolled hypertension defined as sitting SBP > 160 mmHg or DBP > 90 mmHg at Visit 1 or Visit 3
- •Heart rate after 10 minutes sitting rest < 50 bpm or > 100 bpm at Visit 1 or Visit 3
- •eGFR < 60 mL/min/1.73m2 using the Japanese equation
- •Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding. Or participants receiving anti-coagulation therapy
- •History of major bleed or high-risk of bleeding diathesis
- •Subjects with a high 10-year risk of coronary heart disease as calculated using the Suita score
- •Heart rate after 10 minutes of sitting rest < 50 or > 100 beats per minute
- •Uncontrolled hypertension defined as sitting SBP > 140 mmHg or DBP > 90 mmHg
结局指标
主要结局
Part B: Change in LDL-C in Serum at Week 12
时间窗: Baseline to week 12
Part B: Change from baseline in LDL-C at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed. Note: log(week 12 data) - log(baseline data) = log(week12/baseline), which is a ratio
次要结局
- Part B: Percentage Change From Baseline in LDL-C in Serum at Week 12(Measurement at baseline and week 12)
- Part B: Change in PCSK9 in Plasma at Week 12(Baseline to week 12)
- Part B: Percentage Change From Baseline in PCSK9 in Plasma at Week 12(Measurement at baseline and week 12)
- Part A & Part C: AUC (0-24) of AZD8233(Day 1 and Day 57)
- Part A & Part C: Cmax of AZD8233(Day 1 and Day 57)
- Part A & Part C: t1/2 of AZD8233(Day 1 and Day 57)
- Part A & Part C: CL/F (L/h) of AZD8233(Day 1 and Day 57)
- Part A & Part C: Vz/F (L)(Day 1 and Day 57)