A Phase 1, Randomized, Double Blind, Third-party Open, Placebo-controlled, Single And Multiple Dose Escalation, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf-06651600 In Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- 24 hour creatinine clearance (Single Dose)
研究概览
简要总结
This study is a first in human study of PF-06651600. PF-06651600 is being developed for treatment of inflammatory bowel disease. This study will test single and multiple doses of PF-06651600. The goal of the study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-06651600 in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 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/female subjects between 18 and 55 years old, inclusive. Females must be of non-child bearing potential.
- •BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
- •Evidence of personally signed and dated informed consent document.
- •Willing and able to comply with scheduled visits, treatment plan, lab tests and other study procedures.
- •Subjects must avoid high intensity UV light exposure (eg, active sunbathing, tanning beds/booths or sunlamps) from the first dose of study drug and for the duration of the study.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, GI, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
- •Use of tobacco/nicotine containing products in excess of 5 cigarettes/day.
- •History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males.
- •Screening blood pressure >140/90 mm Hg.
- •Screening laboratory abnormalities as defined by the protocol.
- •Unwilling or unable to comply with the Lifestyle Guidelines as defined by the protocol.
研究组 & 干预措施
Cohort 6: PF-06651600 or Placebo
Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
Cohort 1: PF-06651600 or Placebo
Single ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
Cohort 2: PF-06651600 or Placebo
Single ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
Cohort 3: PF-06651600 or Placebo
Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
Cohort 4: PF-06651600 or Placebo
Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
Cohort 5: PF-06651600 or Placebo
Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
Cohort 7: PF-06651600 or Placebo
Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
Cohort 8: PF-06651600 or Placebo
Single ascending doses and multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
Cohort 9: PF-06651600 or Placebo
Multiple ascending doses of PF-06651600 or placebo to evaluate safety, tolerability and PK.
干预措施: PF-06651600 or Placebo (Drug)
结局指标
主要结局
24 hour creatinine clearance (Single Dose)
时间窗: Single dose period, Day 0 (baseline) and 24 hours post dose Day 1.
24 hour urine creatinine clearance in healthy subjects participating in the single dose periods. For the single dose period, assessment occurs on Study Days 0 and 1.
Change from baseline of urine volume (Multiple Dose)
时间窗: Multiple dose period, Days 0 (baseline), 7 and 14.
For the multiple ascending dose period assessments occur on Study Days 7 and 14.
Change from baseline in urine electrolytes (Single Dose)
时间窗: Single dose period, Day 0 (baseline) and 24 hours post dose Day 1.
For the single dose period, assessment occurs on Study Days 0 and 1.
Change from baseline in urine osmolality (Multiple Dose)
时间窗: Multiple dose period, Days 0 (baseline), 7 and 14.
For the multiple ascending dose period assessments occur on Study Days 7 and 14.
24 hour creatinine clearance (Multiple Dose)
时间窗: Multiple dose period, Days 0 (baseline), 7 and 14.
24 hour urine creatinine clearance in healthy subjects participating in the multiple dose period. For the multiple ascending dose period assessments occur on Study Days 7 and 14.
Change from baseline in urine volume (Single Dose)
时间窗: Single dose period, Day 0 (baseline) and 24 hours post dose Day 1.
For the single dose period, assessment occurs on Study Days 0 and 1.
Change from baseline in urine osmolality (Single Dose)
时间窗: Single dose period, Day 0 (baseline) and 24 hours post dose Day 1.
For the single dose period, assessment occurs on Study Days 0 and 1.
Change from baseline of urine electrolytes (Multiple Dose)
时间窗: Multiple dose period, Days 0 (baseline), 7 and 14.
For the multiple ascending dose period assessments occur on Study Days 7 and 14.
次要结局
- Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastdn) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Change from baseline of neutrophil counts in whole blood (Multiple Dose)(Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28)
- Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Time to Reach Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinfdn) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Time to Reach Maximum Observed Plasma Concentration (Cmax) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Dose Normalized Maximum Observed Plasma Concentration (Cmaxdn) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Plasma Decay Half-Life (t1/2) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Apparent Total Body Clearance (CL/F) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Area Under the Curve for Dosing Interval (12 or 24 hours) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Change from baseline of BCL2 gene expression in whole blood (Single Dose)(Days -1 and 1 (0, 1, 2, 4, 8, 12 and 24 hours post dose))
- Change from baseline of IP-10 protein concentration in serum (Multiple Dose)(Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16)
- Plasma Decay Half-Life (t1/2) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Apparent Volume of Distribution (Vz/F) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Amount of PF-066561600 Excreted Unchanged (Multiple Dose)(Day 14 (12, 24 hours post dose))
- Change from baseline of reticulocyte counts in whole blood (Single Dose)(Days 0, 2, 3, and 7)
- Percentage of PF-066561600 Excreted Unchanged (Multiple Dose)(Day 14 (12, 24 hours post dose))
- Minimum Observed Plasma Concentration (Cmin) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Renal Clearance (Multiple Dose)(Day 1, Day 14 (12, 24 hours post dose))
- Change from baseline of IP-10 gene expression in blood (Single Dose)(Days 0, 1 (0, 1, 2, 4, 8 and 12 hours post dose) and 16)
- Mean Resonance Time (MRT) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Mean Resonance Time (MRT) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Apparent Total Body Clearance (CL/F) for PF-06651600 (Single Dose)(0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose)
- Average Concentration for Dosing Interval (12 or 24 hours) (Cav) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Observed Accumulation Ratio (Rac) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Observed Accumulation Ratio for Cmax (RacCmax) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Steady State Accumulation Ratio (Rss) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Change from baseline of neutrophil counts in whole blood (Single Dose)(Days 0, 2, 3, and 7)
- Change from baseline of hemoglobin level whole blood (Single Dose)(Days 0, 2, 3, and 7)
- Change from baseline of hemoglobin level in whole blood (Multiple Dose)(Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28)
- Change from baseline of IP-10 gene expression in blood (Multiple Dose)(Days 0, 5, 10, 14 (0, 1, 2, 4, 8 and 12 hours post dose) and 16)
- Apparent Volume of Distribution (Vz/F) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Dose Normalized Area Under the Curve for Dosing Interval (12 or 24 hours) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Peak to Trough Fluctuation (PTF) for PF-06651600 (Multiple Dose)(Days 1, 4, 6, 8, 10, 12 and 14 (0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post dose))
- Change from baseline of BCL2 gene expression in whole blood (Multiple Dose)(Days 1, 5, 10, 14 (0, 1, 2, 4, 8, 12 and 24 hours post dose), 16, and 28)
- Change from baseline of reticulocyte counts in whole blood (Multiple Dose)(Days 0, 4, 8, 12, 14 (pre-dose) 15, and 28)
- Change from baseline of hsCRP protein concentration in serum (Multiple Dose)(Days 0, 2, 7, 14 (0, and 16 hours post dose) and 16)