A Phase 1, Open Label, Randomized, Single Dose, Dose Escalation Study To Assess The Subcutaneous Pharmacokinetics And Pharmacodynamics Of Bococizumab (pf 04950615) Alone And In Co Mixture With Recombinant Human Hyaluronidase (rhuph20, Pf 06744547) In Healthy And Hypercholesterolemic Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Cmax of bococizumab
研究概览
简要总结
This is a Phase 1, open-label, single-dose, randomized, dose escalation study in healthy and hypercholesterolemic subjects. Each subject will receive 1 of 5 treatments as a single subcutaneous injection. Subjects will remain confined at the research clinic for approximately 2 days. After discharge, subjects will return to the research clinic 15 times during 12 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •* Healthy and hypercholesterolemic subjects between the ages of 18 and 65 years.
- •* Healthy subjects must have fasting LDL-C \>/= 70 to \/= 70 mg/dL.
排除标准
- •Use of prescription or non-prescription drugs within 7 days or 5 half-lives (whichever) is longer prior to the first dose of study medication. For hypercholesterolemic subjects the use of statin class medication is allowed.
- •Prior exposure to bococizumab (also known as PF-04950615 or RN316) or other investigational PCSK9 inhibitors.
- •Treatment with monoclonal antibodies within 6 months or 5 half-lives (whichever is longer) before dosing.
研究组 & 干预措施
Cohort 1: bococizumab 150 mg + rHuPH20
bococizumab 150 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
干预措施: Cohort 1: bococizumab 150 mg + rHuPH20 (Biological)
Cohort 2: bococizumab 300 mg
bococizumab 300 mg administered subcutaneously to healthy volunteers
干预措施: Cohort 2: bococizumab 300 mg (Biological)
Cohort 3: bococizumab 300 mg + rHuPH20
bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
干预措施: Cohort 3: bococizumab 300 mg + rHuPH20 (Biological)
Cohort 5: bococizumab 450 mg + rHUPH20
bococizumab 450 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
干预措施: Cohort 5: bococizumab 450 mg + rHuPH20 (Biological)
Cohort 4: bococizumab 300 mg + rHuPH20
bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to subjects with hypercholesterolemia receiving a statin
干预措施: Cohort 4: bococizumab 300 mg + rHuPH20 (Biological)
结局指标
主要结局
Cmax of bococizumab
时间窗: Day 1 - Day 85
Maximum Observed Plasma Concentration (Cmax)
AUCinf of bococizumab
时间窗: Day 1 - Day 85
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞), if data permits (otherwise AUClast will be used).
次要结局
- CL/F(Day 1 - Day 85)
- Vz/F(Day 1 - Day 85)
- Tmax, LDL-C(Baseline up to Day 85)
- AEs(Baseline up to Day 85)
- Vital signs(Baseline up to Day 85)
- AUClast of bococizumab(Day 1 - Day 85)
- ADA(Day 1 - Day 85)
- Tmax(Day 1 - Day 85)
- t1/2(Day 1 - Day 85)
- MaxELDL-C(Baseline up to Day 85)
- nAb(Day 1- Day 85)
- AUEC85(Baseline up to Day 85)
- Laboratory tests(Baseline up to Day 85)
- LDL-C at Week 4(Baseline to Week 4)