A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenously Administered LGT209 in Healthy Volunteers and Patients With Hypercholesterolemia on Stable Doses of Statin Medications
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in healthy volunteers
研究概览
简要总结
This study is designed to measure the effects of LGT209 when given intravenously to patients with high cholesterol who are on stable doses of statin medications, and to healthy subjects with elevated cholesterol
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers: Male and female subjects 18 to 70 years of age, in general good health but with high cholesterol
- •Statin patients: Male and female patients 18 to 70 years of age, with high cholesterol on stable statin therapy for at least 3 months
排除标准
- •Healthy volunteers: History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
- •Women of child-bearing potential unless using highly effective methods of contraception
- •Statin patients: Use of any prescription drugs for lipid lowering other than HMG CO-A reductase inhibitors (statins); use of two concurrent antihypertensive medications is allowed, provided stable dosing has been achieved for the prior 3 months
- •Women of child-bearing potential unless using highly effective methods of contraception
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Patient: LGT209 0.3 mg/kg
0.3 mg/kg LGT209 intravenous administration in patients on stable doses of statins
干预措施: LGT209 (Drug)
Patient: LGT209 1 mg/kg
1 mg/kg LGT209 intravenous administration in patients on stable doses of statins
干预措施: LGT209 (Drug)
Patient: LGT209 3 mg/kg
3 mg/kg LGT209 intravenous administration in patients on stable doses of statins
干预措施: LGT209 (Drug)
Patient: LGT209 10 mg/kg
10 mg/kg LGT209 intravenous administration in patients on stable doses of statins
干预措施: LGT209 (Drug)
Patient: LGT209 20 mg/kg
20 mg/kg LGT209 intravenous administration in patients on stable doses of statins
干预措施: LGT209 (Drug)
Healthy Volunteers: LGT209 0.3 mg/kg
0.3 mg/kg LGT209 intravenous administration in healthy volunteers
干预措施: LGT209 (Drug)
Healthy Volunteers: LGT209 1 mg/kg
1 mg/kg LGT209 intravenous administration in healthy volunteers
干预措施: LGT209 (Drug)
Healthy Volunteers: LGT209 3 mg/kg
3 mg/kg LGT209 intravenous administration in healthy volunteers
干预措施: LGT209 (Drug)
Healthy Volunteers: LGT209 10 mg/kg
10 mg/kg LGT209 intravenous administration in healthy volunteers
干预措施: LGT209 (Drug)
Healthy Volunteers: 20 mg/kg
20 mg/kg LGT209 intravenous administration in healthy volunteers
干预措施: LGT209 (Drug)
Patient: Placebo
Matching intravenous placebo in patients on stable doses of statins
干预措施: Placebo (Drug)
Healthy Volunteers: Placebo
Matching intravenous placebo in healthy volunteers
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in healthy volunteers
时间窗: Baseline, Day 29
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in healthy volunteers
时间窗: Baseline, Day 29
Baseline was defined as the arithmetic mean of all the pre-treatment values (i.e. Screening, Day -1 and predose on Day 1)
Pharmacokinetics of LGT209: : Area under the serum concentration-time curve from time zero to infinity (AUC0-inf) of LGT209 in patients and healthy volunteers following intravenous administration
时间窗: Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2); 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Pharmacokinetics of LGT209: observed maximum serum concentrations (Cmax) of LGT209 in patients and healthy volunteers following intravenous administration
时间窗: Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Pharmacokinetics of LGT209: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) of LGT209 in patients and healthy volunteers following intravenous administration
时间窗: Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Number of patients with adverse events, serious adverse events and death
时间窗: from Screening until Day 141
Pharmacokinetics of LGT209: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve (T1/2) of LGT209 in patients and healthy volunteers following intravenous administration
时间窗: Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141
Number of healthy volunteers with adverse events, serious adverse events and death
时间窗: from Screening until Day 141
次要结局
- Pharmacokinetics of intravenous LGT209 in relationship to concentrations of PCSK9 and LDL-C in patients and healthy volunteers(Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141)
- Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration in patients(Baseline, Day 29)
- Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients(Baseline, Day 29)
- Pharmacokinetics of LGT209: the systemic (or total body) clearance from serum following intravenous administration(Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141)
- Pharmacokinetics of LGT209: Area under the serum concentration-time curve from time zero to time 't' (AUC0-t)(Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141)
- Pharmacokinetics of LGT209: Dose-normalized area under the serum concentration-time curve (AUC/D) of LGT209 in patients and healthy volunteers following intravenous administration(Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141)
- Pharmacokinetics of LGT209: Dose-normalized maximum serum concentrations (Cmax/D) of LGT209 in patients and healthy volunteers following intravenous administration(Day 1 ( 1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141)
- Pharmacokinetics of LGT209: Volume of distribution during the terminal elimination phase (Vz) of LGT209 in patients and healthy volunteers following intravenous administration(Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141)
- Pharmacokinetics of LGT209: Volume of distribution at steady state (Vss) of LGT209 in patients and healthy volunteers following intravenous administration(Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141)
- Pharmacokinetics of LGT209: Mean residence time (MRT) of LGT209 in patients and healthy volunteers following intravenous administration(Day 1 (1, 2, 4, 6, 8, 12 hrs post dose); Post-dose at 24 hr (Day 2) 48 hr (Day 3), 96 hr (Day 5), Days 8, 11, 15, 22, 29, 43, 57, 71, 85, 113, 141)