A Phase 2 Double Blind, Parallel Group, Placebo Controlled, Randomized, Dose Ranging Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 Following Twice Monthly Subcutaneous Doses In Hypercholesterolemic Japanese Subjects Who Are Receiving A Stable Dose Of Atorvastatin Or Treatment Naïve.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 218
- 试验地点
- 9
- 主要终点
- Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85
研究概览
简要总结
The purpose of this study is to evaluate the low density lipoprotein cholesterol (LDL-C) lowering effect of Bococizumab (PF-04950615;RN316) administered subcutaneously at every two weeks (Q14D) in hypercholesterolemic Japanese subjects whose LDL-C is not controlled by a stable dose of atorvastatin, or who are naïve to a treatment by lipid lowering drug and whose LDL-C is not controlled.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects whose LDL-C is not controlled by a stable dose of atorvastatin (Population A).
- •Subjects who are naïve to a treatment by lipid lowering drug and whose LDL-C is not controlled (Population B).
排除标准
- •Severe acute or chronic medical or psychiatric condition or laboratory abnormality.
- •Pregnant females; breastfeeding females; males and females of childbearing potential; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception.
- •Subjects who were administered or prior exposed to PF-04950615 and/or anti-body targeting PCSK9.
研究组 & 干预措施
Population A
A total of 9 groups in two population. Population A comprises hypercholesterolemic Japanese subjects whose LDL-C is not controlled by a stable dose of atorvastatin. A subject who is receiving a stable dose of atorvastatin will be randomized into one out of 5 dose groups.
干预措施: Bococizumab (PF-04950615;RN316) (Drug)
Population A
A total of 9 groups in two population. Population A comprises hypercholesterolemic Japanese subjects whose LDL-C is not controlled by a stable dose of atorvastatin. A subject who is receiving a stable dose of atorvastatin will be randomized into one out of 5 dose groups.
干预措施: Placebo (Drug)
Population A
A total of 9 groups in two population. Population A comprises hypercholesterolemic Japanese subjects whose LDL-C is not controlled by a stable dose of atorvastatin. A subject who is receiving a stable dose of atorvastatin will be randomized into one out of 5 dose groups.
干预措施: Ezetimibe (Drug)
Population B
A total of 9 groups in two population. Population B comprises hypercholesterolemic Japanese subjects who are naïve for a treatment by lipid lowering drug and whose fasting LDL-cholesterol is not controlled. A subject who is treatment naïve will be randomized into one out of 4 dose groups.
干预措施: Bococizumab (PF-04950615;RN316) (Drug)
Population B
A total of 9 groups in two population. Population B comprises hypercholesterolemic Japanese subjects who are naïve for a treatment by lipid lowering drug and whose fasting LDL-cholesterol is not controlled. A subject who is treatment naïve will be randomized into one out of 4 dose groups.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85
时间窗: Baseline, Day 85
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = (\[observed value divided by baseline value\] minus 1) multiplied by 100.
Percent Change From Baseline in Fasting Low Density Lipoprotein-Cholesterol (LDL-C) at Day 113
时间窗: Baseline, Day 113
LDL-C is cholesterol in the bloodstream that is carried by low density lipoprotein. Fasting was required at least 10 hours before blood sample collection. Baseline was defined as the mean of the last two non-missing measurements collected prior to the first dose of study treatment. Both measurements must be within 10 days prior to the first dose of study treatment; if only one measurement was available 10 days prior to the first dose of study treatment, then that measurement served as the baseline value. Percent change from baseline = (\[observed value divided by baseline value\] minus 1) multiplied by 100.
次要结局
- Low Density Lipoprotein-Cholesterol (LDL-C)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Percent Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113(Baseline, Day 85, 113)
- Lipoprotein (a) (Lp[a])(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- High Density Lipoprotein- Cholesterol (HDL-C)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Percent Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Day 113(Baseline, Day 85, 113)
- Triglyceride (TG)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Change From Baseline in Apolipoprotein A-II (ApoA-II) at Day 85 and Day 113(Baseline, Day 85, 113)
- Change From Baseline in Very Low Density Lipoprotein-Cholesterol (VLDL-C) at Day 85 and Day 113(Baseline, Day 85, 113)
- Non-High Density Lipoprotein- Cholesterol (Non-HDL-C)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Change From Baseline in Non-High Density Lipoprotein- Cholesterol (Non-HDL-C) at Day 85 and Day 113(Baseline, Day 85, 113)
- Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Total Cholesterol (TC)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Percent Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113(Baseline, Day 85, 113)
- Change From Baseline in Apolipoprotein A-I (ApoA-I) at Day 85 and Day 113(Baseline, Day 85, 113)
- Percent Change From Baseline in Apolipoprotein A-II (ApoA-II) at Day 85 and Day 113(Baseline, Day 85, 113)
- Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 85 and Day 113(Baseline, Day 85, 113)
- Percent Change From Baseline in Lipoprotein (a) (Lp[a]) at Day 85 and Day 113(Baseline, Day 85, 113)
- Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Day 85 and Day 113(Baseline, Day 85, 113)
- Change From Baseline in Total Cholesterol (TC) at Day 85 and Day 113(Baseline, Day 85, 113)
- Apolipoprotein B (ApoB)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Change From Baseline in Apolipoprotein B (ApoB) at Day 85 and Day 113(Baseline, Day 85, 113)
- Apolipoprotein A-I (ApoA-I)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Apolipoprotein A-II (ApoA-II)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Percent Change From Baseline in Apolipoprotein A-I (ApoA-I) at Day 85 and Day 113(Baseline, Day 85, 113)
- Very Low Density Lipoprotein-Cholesterol (VLDL-C)(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04950615(Single dose (Day 1: pre-dose, 24, 48, 72, 96, 120, 144, 168 hour (hr) post-dose), Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose))
- Minimum Observed Plasma Trough Concentration (Cmin) of PF-04950615(Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose))
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04950615(Single dose (Day 1: pre-dose, 24, 48, 72, 96, 120, 144, 168 hour (hr) post-dose), Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose))
- Change From Baseline in High Density Lipoprotein- Cholesterol (HDL-C) at Day 85 and Day 113(Baseline, Day 85, 113)
- Percent Change From Baseline in High Density Lipoprotein- Cholesterol (HDL-C) at Day 85 and Day 113(Baseline, Day 85, 113)
- Change From Baseline in Triglyceride (TG) at Day 85 and Day 113(Baseline, Day 85, 113)
- Percent Change From Baseline in Non-High Density Lipoprotein- Cholesterol (Non-HDL-C) at Day 85 and Day 113(Baseline, Day 85, 113)
- Change From Baseline in Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio at Day 85 and Day 113(Baseline, Day 85, 113)
- Percentage of Participants Achieving Low-density Lipoprotein Cholesterol (LDL-C) Less Than (<) 10, 25, 40, 70 and 100 Milligram Per Deciliter(Baseline up to Day 113)
- Percent Change From Baseline in Triglyceride (TG) at Day 85 and Day 113(Baseline, Day 85, 113)
- Percent Change From Baseline in Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio at Day 85 and Day 113(Baseline, Day 85, 113)
- Number of Participants With Anti-Drug Antibody (ADA) Response(Baseline up to Day 169)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-04950615(Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose))
- Maximum Observed Plasma Concentration (Cmax) of PF-04950615(Single dose (Day 1: pre-dose, 24, 48, 72, 96, 120, 144, 168 hr post-dose), Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose))
- Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio(Baseline, Day 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141, 155, 169)
- Change From Baseline in Apolipoprotein B (ApoB) / Apolipoprotein A-I (ApoA-I) Ratio at Day 85 and Day 113(Baseline, Day 85, 113)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)(Baseline up to Day 169)
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of PF-04950615(Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose))
- Plasma Concentration of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)(Day 1, 5, 8, 15, 22, 29, 36, 43, 50, 57, 71, 85, 99, 106, 113, 127, 141)
- Percent Change From Baseline in Total Cholesterol (TC) / High Density Lipoprotein- Cholesterol (HDL-C) Ratio at Day 85 and Day 113(Baseline, Day 85, 113)
- Terminal Elimination Half-Life (t1/2) of PF-04950615(Multiple dose (Day 99: pre-dose, 24, 72, 120, 168, 336, 504, 672, 1008 hr post-dose))