A Phase 1, Open-label, Randomized, Single Dose, Parallel Group Study To Assess The Pharmacokinetics And Pharmacodynamics Of Pf-04950615 Following Subcutaneous And Intravenous Doses In Adult Subjects With Hypercholesterolemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 49
- 试验地点
- 14
- 主要终点
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
研究概览
简要总结
This Phase 1 study has been designed to evaluate the absolute bioavailability of PF-04950615 (RN316) in subjects with hypercholesterolemia who are not currently on lipid-lowering therapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Fasting LDL-C greater than or equal to 130 mg/dL at two qualifying screening visits.
- •Total body weight greater than or equal to 50 kg (110 lbs) and less than or equal to 150 kg (330 lbs)
排除标准
- •Lipid-lowering prescription medications, homeopaths, herbal medicines, or nutritional supplements.
- •Poorly controlled type 1 or type 2 diabetes.
- •History of a cardiovascular or cerebrovascular event or related procedure during the past year.
- •Poorly controlled hypertension.
结局指标
主要结局
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of PF-04950615
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time Zero To Infinity (AUCinf) of PF-04950615
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Apparent Volume of Distribution (Vz/F) of PF-04950615 Subcutaneous Groups
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Volume of distribution (Vz) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction of the dose absorbed from plasma after SC administration of drug.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of PF-04950615
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Terminal Elimination Half-life (t1/2) of PF-04950615
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
t1/2 is the time measured for the plasma concentration of drug to decrease by one half.
Apparent Clearance (CL/F) of PF-04950615 Subcutaneous Groups
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance (CL/F) is influenced by the fraction of the dose absorbed from plasma after SC administration of drug.
Clearance (CL) of PF-04950615 Intravenous Group
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Volume of Distribution at Steady State (Vss) of PF-04950615 Intravenous Group
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is determined when overall intake of drug is in dynamic equilibrium with its elimination.
Absolute Bioavailability of PF-04950615 Subcutaneous Groups
时间窗: Pre-dose, 30 minutes, 1, 8, 24, 48, 72, 96, 120, 168, 336, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 2016 hours post-dose
Bioavailability is defined as the rate and extent to which the active moiety administered drug reaches the systemic circulation. Absolute bioavailability of the subcutaneous doses was estimated by comparing log-transformed dose-normalized AUClast for subcutaneous to intravenous dose.
次要结局
- Absolute Value of Fasting Low-density Lipoprotein Cholesterol (LDL-C)(Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85)
- Duration of Fasting LDL-C Suppressed Below 70 mg/dL and 100 mg/dL(Day 1 up to Day 85)
- Percent Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) at Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 85(Baseline, Day 2, 3, 4, 5, 6, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85)