A Single-Dose, Open-Label, Parallel-Group Study to Assess the Pharmacokinetics of Inclisiran in Subjects With Renal Impairment Compared to Subjects With Normal Renal Function (ORION-7)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Pharmacokinetics: Tmax And t1/2 Of Inclisiran
研究概览
简要总结
This study is a Phase I, single-dose, open-label trial to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a single dose of inclisiran subcutaneous (SC) injection in participants with mild, moderate, and severe renal impairment compared to participants with normal renal 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
- Treatment
- 盲法
- None
盲法说明
Open-Label
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female participants 18 to 80 years of age
- •Participants should be qualified for inclusion based upon estimated CrCl ranges for normal renal function group and mild, moderate, and severe renal impairment groups
排除标准
- •Participants with acute renal disease and/or history of renal transplant
- •Urinary incontinence without catheterization
- •Participants requiring hemodialysis
- •Participants with LDL-C <60 mg/deciliter (dL) (or less than 1.55 millimoles/liter [mmol/L])
- •Participants with Amyloid Kidney (if known by pathology)
- •Participants with any significant hepatic, cardiac, or pulmonary disease or participants who are clinically nephritic
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Inclisiran (normal renal function)
Participants will receive a single dose of 300 milligram (mg) inclisiran administered by SC injection on Day 1. Normal renal function is defined as estimated creatinine clearance (CrCl) of ≥90 milliliter (mL)/minute (min).
干预措施: Inclisiran (Drug)
Inclisiran (mild renal impairment)
Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Mild renal impairment is defined as CrCl ranging from 60 to 89 mL/min.
干预措施: Inclisiran (Drug)
Inclisiran (moderate renal impairment)
Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Moderate renal impairment is defined as CrCl ranging from 30 to 59 mL/min.
干预措施: Inclisiran (Drug)
Inclisiran (severe renal impairment)
Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Severe renal impairment is defined as CrCl ranging from 15 to 29 mL/min.
干预措施: Inclisiran (Drug)
结局指标
主要结局
Pharmacokinetics: Tmax And t1/2 Of Inclisiran
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post dose
Measurement of effect of renal impairment on PK of inclisiran by assessment of time to reach maximum plasma concentration (Tmax) and time for inclisiran to reach half of its initial value (t1/2). Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Pharmacokinetics: AUC0-24, AUC0-48, And AUC0-inf Of Inclisiran
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post dose
Measurement of effect of renal impairment on PK of inclisiran by assessment of area under the curve of the plasma concentration (AUC) from time 0 to 24 hours (AUC0-24), from time 0 to 48 hours (AUC0-48), and from time 0 extrapolated to infinity (AUC0-inf). Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) Of Inclisiran
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post-dose
Measurement of effect of renal impairment on PK of inclisiran by assessment of Cmax. Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Pharmacokinetics: Vd/F During The Terminal Elimination Phase Following SC Administration Of Inclisiran
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post dose
Measurement of effect of renal impairment on PK of inclisiran by assessment of apparent volume of distribution (Vd/F) of inclisiran during the terminal elimination phase. Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Pharmacokinetics: Renal Clearance (CLr) Of Inclisiran
时间窗: 0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals
Measurement of effect of renal impairment on PK of inclisiran by assessment of CLr, calculated as Ae/AUC0-48 plasma. CLr will be calculated if possible (for example, if the percent of unchanged drug excreted in urine exceeds 20%). Pooled urine samples will be used for the analysis.
Pharmacokinetics: Fraction Excreted (Fe) Of Inclisiran
时间窗: 0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals
Measurement of effect of renal impairment on PK of inclisiran by assessment of the urinary recovery rate over a specific collection interval (Fe), calculated as 100\*Ae/Dose. Pooled urine samples will be used for the analysis.
Pharmacokinetics: Apparent Total Clearance (CL/F) Following SC Administration Of Inclisiran
时间窗: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose and Day 4, Day 7, Day 14, and Day 30 post dose
Measurement of effect of renal impairment on PK of inclisiran by assessment of CL/F. Serial blood samples will be collected for the analysis. PK parameters will be determined from the plasma concentration-time profiles using a noncompartmental approach.
Pharmacokinetics: Amount Excreted Unchanged In Urine (Ae) Of Inclisiran Over 48 Hours Post-Dose
时间窗: 0 up to 6 hours, 6 up to 12 hours, 12 up to 24 hours, and 24 up to 48 hour post-dose intervals
Measurement of effect of renal impairment on PK of inclisiran by assessment of Ae of inclisiran. Pooled urine samples will be used for the analysis.
次要结局
- Change From Baseline In Lipids And Lipoproteins At Day 60(Baseline, Day 60)
- Change From Baseline In PCSK9 At Day 60(Baseline, Day 60)