A Phase I, Open-label Single Dose Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Subjects With Various Degrees of Hepatic Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Maximum Observed Serum Concentration (Cmax) of Olpasiran
研究概览
简要总结
The primary objective of the study is to evaluate the pharmacokinetics (PK) of a single dose of olpasiran in participants with mild, moderate, or severe hepatic impairment compared to participants with normal hepatic function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female participants of nonchildbearing potential, between 18 and 75 years of age (inclusive) at the time of Screening.
- •Body mass index between 18.0 and 40.0 kg/m^2 (inclusive) at the time of Screening.
- •Participants with Normal Hepatic Function Only:
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations at Screening and Check-in as assessed by the Investigator (or designee).
- •Participants with Hepatic Impairment Only:
- •Child-Pugh A (Group 2), B (Group 3), or C (Group 4) classification defined by both Screening (to determine participant group) and Check-in (to confirm participant group prior to dosing) clinical laboratory values and physical examination findings.
排除标准
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- •Estimated glomerular filtration rate < 60 mL/min/1.73m^2 (Groups 1-3) or < 50 mL/min/1.73m^2 (Group 4 only) by Modification of Diet in Renal Disease formula at Screening or Check-in.
- •Receiving or has received any investigational drug within the 30 days or 5 half-lives (whichever is longer) before receiving olpasiran.
- •Participants who were previously exposed to olpasiran.
- •Female participants with a positive pregnancy test at Screening or Check-in.
- •Participants with Normal Hepatic Function Only:
- •Positive hepatitis panel. Participants whose results are compatible with prior immunization may be included.
- •Alanine aminotransferase and aspartate aminotransferase elevations > 3x upper limit of normal at Screening or Check-in.
- •Participants with Hepatic Impairment Only:
- •Positive for hepatitis B surface antigen. Participants with positive hepatitis B core antibody may be included if hepatitis B surface antigen is negative. Participants with positive hepatitis B surface antibody may be included (consistent with prior vaccination).
- •Active malignancy of any type. Participants with a history of malignancy that has been eradicated with supporting medical documentation indicating that there is no residual malignancy detected in the past 2 years will be allowed.
- •Values outside the normal range for liver function tests that are not consistent with their hepatic condition, as determined by the Investigator (or designee).
研究组 & 干预措施
Single Dose Olpasiran Hepatic Impairment
Participants will be enrolled in 1 of 3 hepatic impairment groups based on their hepatic impairment status, as determined by Child-Pugh classification. All participants will receive a single dose of olpasiran on Day 1.
干预措施: Olpasiran (Drug)
Single Dose Olpasiran Normal Hepatic Function
Participants with normal hepatic function will be enrolled and will receive a single dose of olpasiran on Day 1.
干预措施: Olpasiran (Drug)
结局指标
主要结局
Maximum Observed Serum Concentration (Cmax) of Olpasiran
时间窗: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Olpasiran
时间窗: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Olpasiran
时间窗: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
次要结局
- Number of Participants with Clinically Significant Changes in Vital Signs(Up to Day 85)
- Maximum Inhibitory Effect (Imax) of Plasma Lp(a)(Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85)
- Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations(Up to Day 85)
- Number of Participants Who Experience an Adverse Event (AE)(Up to Day 85)
- Area Under the Effect Time Curve (AUEC) of Plasma Lipoprotein a (Lp[a])(Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85)
- Time to Reach Imax of Lp(a)(Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85)
- Number of Participants With Clinically Significant Changes 12-lead Electrocardiogram (ECG) Measurements(Up to Day 85)