A Placebo-controlled, Participant, Investigator and Sponsor Blinded, Randomized Study to Evaluate the Pharmacokinetics and Pharmacodynamics of Inclisiran Treatment Given as Single Subcutaneous Injection in Chinese Participants With Elevated Low-density Lipoprotein Cholesterol (LDL-C) Despite Treatment With LDL-C Lowering Therapies (ORION-14)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants
研究概览
简要总结
Study to evaluate the pharmacokinetics and pharmacodynamics of inclisiran treatment given as single subcutaneous injection in Chinese participants with elevated low-density lipoprotein cholesterol (LDL-C) despite treatment with LDL-C lowering therapies
详细描述
The purpose of the study is to characterize pharmacokinetics, pharmacodynamics, safety and tolerability of inclisiran in Chinese participants with elevated serum LDL-C to support inclisiran registration in China.Inclisiran is a long acting RNA therapeutic agent that inhibits the synthesis of PCSK9, leading to reduced circulating LDL-C levels. Three pivotal Phase III studies have been conducted primarily in non-Asian participants to support New Drug Application/Marketing Authorization Application approval of inclisiran globally. This study design is based on the hypothesis that the global inclisiran clinical data primarily obtained in Caucasian participants could be appropriately extrapolated to Chinese participants.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a participant, investigator and sponsor blinded, randomized study
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any assessment is performed.
- •Male or female participants ≥ 18 years of age at screening
- •Participants should meet fasting serum LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) at screening
- •Participants should meet fasting triglyceride < 400 mg/dL (< 4.52 mmol/L) at screening
- •Participants should be receiving a maximally tolerated dose of statin#.
- •For all participants, all the lipid-lowering therapy/ies (such as but not limited to statins and/or ezetimibe) should have remained stable (stable dose and no medication change) for ≥ 30 days before screening with no planned medication or dose change during study participation. #Maximum tolerated dose was defined as the maximum dose of statin that could be taken on a regular basis without intolerable AEs.
- •Participants not receiving statin must have a documented evidence of intolerance to all doses of at least 2 different statins (or the corresponding local definition of complete intolerance to statins)
排除标准
- •Participants diagnosed with any of following: homozygous familial hypercholesterolemia, New York Heart Association class III & IV heart failure, Type 2 diabetes, severe hypertension, active liver disease, HIV infection or any uncontrolled or serious disease;
- •History of drug abuse or unhealthy alcohol use, malignancy of any organ system, or or allergy to the investigational compound/compound class;
- •Major adverse cardiovascular event within 3 months prior to randomization;
- •Calculated glomerular filtration rate ≤30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology;
- •Use of other investigational drugs or planned use of other investigational products or devices;
- •Women of child-bearing potential unless they are using basic methods of contraception during dosing of investigational drug (total abstinence, sterilization, barrier methods, hormonal contraception, intrauterine device);
- •Treatment with monoclonal antibodies inhibiting PCSK9 within 90 days prior to screening.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
300 mg inclisiran sodium (equivalent to 284 mg inclisiran)
300 mg inclisiran sodium (equivalent to 284 mg inclisiran) x 1 dose (n=15) at Day 1
干预措施: 300 mg inclisiran sodium (equivalent to 284 mg inclisiran) (Drug)
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) x 1 dose (n=15) at Day 1
干预措施: 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) (Drug)
Placebo
Placebo x 1 dose (n=10) at Day 1
干预措施: Placebo (Drug)
结局指标
主要结局
PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants
时间窗: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
PK parameters (Tmax) time to reach maximum peak plasma inclisiran concentration in treated participants
时间窗: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
PK parameters (T1/2) the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve in inclisiran treated participants
时间窗: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
PK parameters (AUC) area under the plasma concentration-time curve in inclisiran treated participants
时间窗: 0-48 hours post-dose
Pharmacokinetics parameters of inclisiran
Percentage change in Proprotein convertase subtilisin kexin 9 (PCSK9) from baseline overtime
时间窗: Baseline to Days 5, 8, 15, 30, 60 and 90
Pharmacodynamics effects of inclisiran
Percentage change in Low density lipoprotein cholesterol (LDL-C) from baseline overtime
时间窗: Baseline to Days 5, 8, 15, 30, 60 and 90
Pharmacodynamics effects of inclisiran
次要结局
- Percent change from baseline to Days 30, 60 and 90 in PD parameter Low density lipoprotein cholesterol (LDL-C)(Baseline to Days 30, 60 and 90)
- Rate of formation of anti-drug antibodies to Inclisiran(Baseline, Days 30 and 90)
- Percent change from baseline to Days 30, 60 and 90 in PD parameter Proprotein convertase subtilisin kexin 9 (PCSK9)(Baseline to Days 30, 60 and 90)