NCT04987320已完成1 期
An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Olpasiran in Chinese Subjects With Elevated Serum Lipoprotein(a)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum Observed Concentration (Cmax) of Olpasiran
研究概览
简要总结
The main objective of this study is to evaluate the pharmacokinetics (PK) of a single dose of Olpasiran in Chinese participants with elevated serum lipoprotein(a) (Lp[a]).
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
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion eligibility criteria will be evaluated in 2 parts during the screening period:
- •Part 1: After written informed consent is obtained, subjects will provide a blood sample for a preliminary Lp(a) assessment to determine eligibility for Part 2 screening. Subjects with Lp(a) ≥ 70 nmol/L (or approximately ≥ 27 mg/dL) will be eligible to return to the CRU Part 2 screening. Subjects not eligible to return for Part 2 screening will be screen failed.
- •Part 2: Eligible subjects will complete all remaining screening procedures and tests that establish eligibility within 40 days prior to the Day 1 visit.
- •Must be a resident in mainland China, Hong Kong, or Taiwan, and of Chinese Ancestry.
- •Male or female subjects, between 18 and 60 years of age (inclusive) at the time of Screening.
- •Screening serum Lp(a) ≥ 70 nmol/L (or approximately ≥ 27 mg/dL).
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) as assessed by the Investigator (or designee).
- •Body mass index between 18 and 32 kg/m^2 (inclusive) at the time of Screening.
- •Subjects who are on statin must be on a stable dose of the same statin for at least 6 weeks prior to enrollment, and plan to remain on a stable dose (i.e., no change in medication or dosage) for the duration of the study.
- •Females must be of non-reproductive potential:
- •a. Postmenopausal defined as: i. Age of ≥ 55 years with no menses for at least 12 months; OR ii. Age of < 55 years with no menses for at least 12 months AND with a follicle stimulating hormone (FSH) level > 40 IU/L or according to the definition of "postmenopausal range" for the laboratory involved; OR b. History of hysterectomy; OR c. History of bilateral oophorectomy.
排除标准
- •History or clinical evidence of peripheral neuropathy.
- •Currently receiving apheresis as lipid reducing therapy.
- •History or clinical evidence of bleeding diathesis or any coagulation disorder, including prothrombin time (PT), activated partial thromboplastin time (APTT), or platelet count outside of the laboratory's normal reference range at screening. Subjects with PT and/or APTT values that are outside of the laboratory's normal reference range at screening may still be eligible to proceed to enrollment if the results are judged by the investigator in consultation with the study medical monitor to not be clinically significant.
- •History or clinical evidence of diabetes mellitus, including a fasting glucose ≥ 125 mg/dL (6.9 mmol/L) at Screening.
- •Use of any herbal medicines, vitamins or dietary supplements known to affect lipid metabolism (e.g. sigh oils > 100mg/day, red yeast extract), within 30 days prior to dosing on Day 1 and for the duration of the study.
研究组 & 干预措施
Olpasiran Dose A
Experimental
Participants will be administered Olpasiran dose A as a subcutaneous injection.
干预措施: Olpasiran (Drug)
Olpasiran Dose B
Experimental
Participants will be administered Olpasiran dose B as a subcutaneous injection.
干预措施: Olpasiran (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of Olpasiran
时间窗: Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85
The serum pharmacokinetic (PK) parameters of olpasiran were calculated using standard noncompartmental methods.
次要结局
- Apparent Terminal Elimination Half-life (T1/2) of Olpasiran(Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85)
- Apparent Total Body Clearance (CL/F) of Olpasiran(Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85)
- Area Under the Serum Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Olpasiran(Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85)
- Percentage Change From Baseline in Triglycerides(Baseline and Days 7, 15, 57, 155 and 225)
- Time to Cmax (Tmax) of Olpasiran(Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85)
- Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Olpasiran(Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85)
- Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Olpasiran(Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85)
- Percentage Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)(Baseline and Days 7, 15, 57, 155 and 225)
- Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)(Up to Day 225)
- Percentage Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)(Baseline and Days 7, 15, 57, 155 and 225)
- Percentage Change From Baseline in Total Cholesterol(Baseline and Days 7, 15, 57, 155 and 225)
- Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)(Baseline and Days 7, 15, 57, 155 and 225)
- Percentage Change From Baseline in Apolipoprotein A1 (ApoA1)(Baseline and Days 7, 15, 57, 155 and 225)
- Percentage Change From Baseline in Lipoprotein-a (Lp[a])(Baseline and Days 2, 4, 7, 15, 29, 57, 85, 113, 155, 183 and 225)
- Percentage Change From Baseline in Apolipoprotein B (Apo B)(Baseline and Days 7, 15, 57, 155 and 225)
研究者
研究点 (1)
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