A Phase I, Placebo Controlled, Randomized, Subject-And Investigator-Blind, Sponsor-Open, Multiple Ascending Dose Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-05180999 In Healthy Adult Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Pfizer
- 主要终点
- Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
PF-05180999 is a novel phosphodiesterase-2 (PDE2) inhibitor. The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple doses of PF-05180999 administered twice daily over 14 days. Exploratory measures of PDE2 inhibition will also be evaluated in blood and blister fluid.
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/or female (of non-childbearing potential) subjects between the ages of 18 and 55 years
- •Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)
排除标准
- •Subjects with Gilbert's disease or screening laboratory test results that deviate from the upper and/or lower limits of the reference or acceptable range. The exception is that all liver function tests must not exceed the upper limit of normal.
- •Subjects with evidence of, or history of, hepatic disorder, including acute or chronic hepatitis B or hepatitis C.
- •Subjects with very light skin or very dark skin (at the discretion of the investigator).
研究组 & 干预措施
Placebo
Placebo tablets
干预措施: Placebo Tablets (Drug)
PF-05180999
Modified-release tablets of PF-05180999
干预措施: PF-05180999 Tablets (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax)
时间窗: 0-12 hours post-dose on Day 1
Single dose Cmax
Time to Reach Maximum Observed Plasma Concentration (Tmax)
时间窗: 0-12 hours post-dose on Day 1
Single dose Tmax
Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
时间窗: 0-12 hours post-dose on Day 1
Single dose AUCtau
Maximum Observed Plasma Concentration at Steady-State (Cmax,ss)
时间窗: 0-12 hours post-dose on Day 14
Steady-state Cmax
Time to Reach Maximum Observed Plasma Concentration at Steady-State (Tmax,ss)
时间窗: 0-12 hours post-dose on Day 14
Steady-state Tmax
Minimum Observed Plasma Trough Concentration at Steady-State (Cmin,ss)
时间窗: 0-12 hours post-dose on Day 14
Steady-state Cmin
Area Under the Curve from Time Zero to End of Dosing Interval at Steady-State (AUCtau,ss)
时间窗: 0-12 hours post-dose on Day 14
Steady-state AUCtau
Apparent Oral Clearance (CL/F)
时间窗: 0-48 hours post-final dose on Day 14
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Volume of Distribution (Vz/F)
时间窗: 0-48 hours post-final dose on Day 14
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Plasma Decay Half-Life (t1/2)
时间窗: 0-48 hours post-final dose on Day 14
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Accumulation Ratio (Racc)
时间窗: 0-12 hours post-dose on Days 1 and 14
Ratio of Day 14 AUCtau to Day 1 AUCtau
Amount Excreted in Urine (Ae)
时间窗: 0-12 hours post-dose on Day 14
Amount of drug excreted in urine
Percent of Dose Excreted in Urine (Ae%)
时间窗: 0-12 hours post-dose on Day 14
Percent of total dose excreted in urine
Renal Clearance (CLr)
时间窗: 0-48 hours post-dose on Day 14
Renal clearance is a quantitative measure of the rate at which a drug substance is removed from the blood via the renal route.
次要结局
- Identification of metabolites of PF-05180999 in urine and plasma(0-12 hours post-dose on Day 14)
- Change from Baseline in Total Leukocyte Levels and Leukocyte Subpopulations in Blister Fluid and Blood(Day 13 and Day 14)
- Change from Baseline in Cytokine Levels in Blister Fluid(Day 13 and Day 14)
- Time-Averaged Area Under the Effect Curve (AUEC/t) for Platelet cGMP and cAMP(0-12 hours post-dose on Day 1 and Day 14)
- AUEC/t Ratio(0-12 hours post-dose on Day 1 and Day 14)
- Urinary 6beta-hydroxycortisol/cortisol ratio(Day 14)
- Plasma 4beta-hydroxycholesterol/cholesterol ratio(Day 14)