A Phase 1, Placebo-Controlled, Crossover, Subject- And Investigator-Blind, Sponsor-Open Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Effects On Histamine-Induced Wheal Of A Modified-Release Formulation Of PF-05180999 In Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Plasma Half-Life (t1/2)
研究概览
简要总结
PF-05180999 is a phosphodiesterase-2 inhibitor that is hypothesized to be able to reduce vascular permeability. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and effects on histamine-induced wheal of single doses of PF-05180999 in healthy adult subjects. Histamine-induced wheals are biomarkers of vascular permeability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects between the ages of 18 and 55 years
- •No history of clinically-relevant atopic or dermatological disease
- •Positive reaction to intradermal injection of histamine
排除标准
- •Subjects with 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
- •Intolerance to intradermal histamine injection.
- •Subjects with dark skin (Part B only).
研究组 & 干预措施
Arm A1
Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999
干预措施: PF-05180999 (Drug)
Arm A2
Part A of study to assess safety, tolerability, and pharmacokinetics of PF-05180999 relative to placebo
干预措施: Placebo (Drug)
Arm B1
Part B of study to assess effects of PF-05180999 on histamine-induced wheal
干预措施: 120 mg MR PF-05180999 (Drug)
Arm B2
Part B of study to assess effects of PF-05180999 on histamine-induced wheal
干预措施: 360 mg MR PF-05180999 (Drug)
Arm B3
Positive control to ensure histamine-induced wheal assay integrity
干预措施: 10 mg cetirizine (Drug)
Arm B4
Placebo control
干预措施: Placebo (Drug)
结局指标
主要结局
Plasma Half-Life (t1/2)
时间窗: 0-72 hours post-dose
Time for the plasma concentration to decrease by one-half.
Area Under the Effect Curve (AUEC) for Histamine-Induced Wheal
时间窗: 2-12 hours post-dose
Measure of drug effect
Maximum Observed Plasma Concentration (Cmax)
时间窗: 0-72 hours post-dose
Maximum observed plasma concentration
Time to Reach Maximum Observed Plasma Concentration (Tmax)
时间窗: 0-72 hours post-dose
Time when Cmax occurred
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)
时间窗: 0-72 hours post-dose
Measure of drug absorption and drug exposure
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf)
时间窗: 0-infinity hours post-dose
Measure of drug absorption and drug exposure
次要结局
- Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced wheal(0-72 hours post-dose)
- Area Under the Effect Curve (AUEC) for histamine-induced flare; Dose-response, exposure-response, and maximum response for PF-05180999 against histamine-induced flare(0-72 hours post-dose)