A Phase 1, Randomized, Double-blind, Placebo-controlled Study To Assess Safety, Tolerability, And Pharmacokinetics Of Multiple Oral Doses Of Pf-06835919 In Healthy Adult Subjects (Part A); And An Open-label Study To Assess Multiple Oral Doses Of Pf-06835919 On Atorvastatin Pharmacokinetics (Part B)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 3 of atorvastatin and 2 active metabolites
研究概览
简要总结
Part A will investigate the safety, tolerability, PK and PD of PF-06835919 administered for 14 days in a multiple ascending dose design. Part B will assess the effect of PF-06835919 co-administration at low and high doses on the PK of atorvastatin in a single cohort.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and females (nonchildbearing potential)
- •18 to 55 years old
- •Body Mass Index 17.5 to 30.5
排除标准
- •Known hereditary fructose intolerance or fructose malabsorption disorder (Part A)
- •Statin intolerance (Part B)
- •Unable to consume high fructose syrup-containing beverage with each meal while in the unit (Part A)
研究组 & 干预措施
Placebo
Tablets administered once or twice daily, with food, in Part A for 14 days.
干预措施: Placebo (Drug)
PF-06835919
Tablets administered once or twice daily, with food, in Part A for 14 days. Tablets administered once or twice daily, for 4 days at a low dose and for 4 days at a higher dose, with food and atorvastatin in Part B.
干预措施: PF-06835919 (Drug)
PF-06835919
Tablets administered once or twice daily, with food, in Part A for 14 days. Tablets administered once or twice daily, for 4 days at a low dose and for 4 days at a higher dose, with food and atorvastatin in Part B.
干预措施: atorvastatin (Drug)
atorvastatin
In Part B, tablets administered once or twice daily, with food, with and without a low dose of PF-06835919 for 4 days and a higher dose of PF-06835919 for 4 days.
干预措施: PF-06835919 (Drug)
atorvastatin
In Part B, tablets administered once or twice daily, with food, with and without a low dose of PF-06835919 for 4 days and a higher dose of PF-06835919 for 4 days.
干预措施: atorvastatin (Drug)
结局指标
主要结局
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 3 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Maximum Observed Plasma Concentration (Cmax) on Day 3 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Number of Participants With Clinical Laboratory Abnormalities
时间窗: Day -2 to Day 24
Part A
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
时间窗: Screening to Day 24
Part A
Change from baseline in 12-lead electrocardiogram
时间窗: Day -1 to Day 24
Part A
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day 7 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day -1 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Maximum Observed Plasma Concentration (Cmax) on Day 7 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Plasma Decay Half-Life (t1/2) on Day 3 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Change from baseline in vital signs
时间窗: Day -1 to Day 24
Part A
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day -1 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day 3 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Plasma Decay Half-Life (t1/2) on Day -1 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Maximum Observed Plasma Concentration (Cmax) on Day -1 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) on Day 3 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) on Day 7 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
Plasma Decay Half-Life (t1/2) on Day 7 of atorvastatin and 2 active metabolites
时间窗: 0,0.5,1,1.5,2,3,4,6,9,12,24,36 and 48 hours post-atorvastatin dose
Part B
次要结局
- Maximum Observed Plasma Concentration (Cmax) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48, and 72 hours post-dose)
- Minimum Observed Plasma Trough Concentration (Cmin) on Day 7 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Accumulation Ratio (Rac) on Day 7 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Accumulation Ratio (Rac) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Plasma Decay Half-Life (t1/2) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Maximum Observed Plasma Concentration (Cmax) on Day 7 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 7 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Maximum Observed Plasma Concentration (Cmax) on Day 1 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 7 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Apparent Volume of Distribution (Vz/F) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Change from Baseline in Vital Signs(Day -2 to Day 18)
- Change from baseline in 12-lead electrocardiogram(Day -2 to Day 18)
- Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 1 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Apparent Oral Clearance (CL/F) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) on Day 7 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Renal Clearance (CLr) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)(Screening to Day 18)
- Number of Participants With Clinical Laboratory Abnormalities(Day -2 to Day 18)
- Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Apparent Oral Clearance (CL/F) on Day 7 Part A(0,0.5,1,2,4,5,6,8 and 12 hours post-dose)
- Minimum Observed Plasma Trough Concentration (Cmin) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Cumulative Amount of Drug Recovered Unchanged in Urine (Ae) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)
- Percent Cumulative Amount of Drug Recovered Unchanged in Urine (Ae%) on Day 14 Part A(0,0.5,1,2,4,5,6,8,12,14,16,24,36,48 and 72 hours post-dose)