A Phase 1, 3-part Study Of Pf-05221304 In Healthy Adults: Part 1 - Randomized, Double-blind, Placebo-controlled Assessment Of Safety And Pharmacokinetics Of Single, Escalating, Oral Doses; Part 2 - Randomized, Double-blind, Placebo-controlled Assessment Of Safety And Pharmacokinetics Of Repeated, Escalating, Oral Doses; Conditional Part 3 - Effect Of Food On The Pharmacokinetics Of Pf-05221304
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Part 3: Plasma Decay Half-Life (t1/2) for PF-05221304 (as permitted)
研究概览
简要总结
The current study is the first clinical trial proposed with PF-05221304. It is designed to evaluate the safety, tolerability, and pharmacokinetics (PK) following administration of single and repeated doses of PF-05221304 to healthy adult subjects. The study may also evaluate effect of food on PK of PF-05221304.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 males and female of non-childbearing potential;
- •Body Mass Index 17.5-30.5 kg/m2;
- •Body weight >50 kg;
排除标准
- •Evidence of history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergises, but excluding untreated, asymptomatic, seasonal allergies at time of dosing
研究组 & 干预措施
Part 1_Cohort 1_Placebo
Single dose of Placebo
干预措施: Placebo (Other)
Part 1_Cohort 1_Active
Single, escalating dose of PF-05221304
干预措施: PF-05221304 (Drug)
Part 1_Cohort 2_Active
Single, escalating dose of PF-05221304
干预措施: PF-05221304 (Drug)
Part 1_Cohort 2_Placebo
Single dose of Placebo
干预措施: Placebo (Other)
Part 2_Active
Repeated, escalating doses of PF-05221304
干预措施: PF-05221304 (Drug)
Part 2_Placebo
Repeated doses of placebo
干预措施: Placebo (Other)
Part 3
Single dose of PF-05221304 with and without food
干预措施: PF-05221304 (Drug)
结局指标
主要结局
Part 3: Plasma Decay Half-Life (t1/2) for PF-05221304 (as permitted)
时间窗: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose
Plasma Decay Half-Life (t1/2)
Part 1: Number of Subjects experiencing an Adverse Event
时间窗: Screening up to 28 days after last dose of study medication
Assessment by adverse event monitoring, 12 lead ECGs, telemetry, vital signs and clinical safety laboratory measurements. Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug was assessed by the investigator (Yes/No). Subjects with multiple occurrences of an AE within a category were counted once within the category.
Part 2: Number of Subjects experiencing an Adverse Event
时间窗: Screening up to 28 days after last dose of study medication
Assessment by adverse event monitoring, 12 lead ECGs, telemetry, vital signs and clinical safety laboratory measurements. Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug was assessed by the investigator (Yes/No). Subjects with multiple occurrences of an AE within a category were counted once within the category.
Part 3: Maximum Observed Plasma Concentration (Cmax) for PF-05221304
时间窗: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose
Maximum Observed Plasma Concentration (Cmax)
Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05221304
时间窗: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Part 3: Apparent Total Body Clearance (CL/F) for PF-05221304 (as permitted)
时间窗: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose
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 apparent total body clearance is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Part 3: Apparent Volume of Distribution (Vz/F) for PF-05221304 (as permitted)
时间窗: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose
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.
Part 3: Time to Reach Maximum Observed Concentration for PF-05221304
时间窗: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Part 3: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] for PF-05221304 (as permitted)
时间窗: 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose
AUC (0-infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (t-infinity).
次要结局
- Part 2: Multiple-dose plasma parameters of Plasma Decay Half-Life (t1/2) for PF-05221304 (as permitted)(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours on Day 1 and 7, and 0 hr on Day 2, Day 4, Day 8, Day 10, Day 13, Day 15, and Day 16 post dose)
- Part 1: Apparent Total Body Clearance (CL/F) for PF-05221304 (as permitted)(0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose)
- Part 2: Multiple-dose plasma parameters of Tmax for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted))
- Part 2: Multiple-dose plasma parameters of AUCtau for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted))
- Part 2: Multiple-dose plasma parameters of CL/F for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted))
- Part 2: Single-dose plasma parameters of Tmax for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Day 1)
- Part 2: Multiple-dose plasma parameters of Peak-trough ratio (PTR) for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted))
- Part 2: Multiple-dose plasma parameters of Observed accumulation ratio (Rac(AUCtau))(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted))
- Part 1: Time to Reach Maximum Observed Concentration for PF-05221304(0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose)
- Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] for PF-05221304 (as permitted)(0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose)
- Part 1: Apparent Volume of Distribution (Vz/F) for PF-05221304 (as permitted)(0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose)
- Part 1:Maximum Observed Plasma Concentration (Cmax) for PF-05221304(0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose)
- Part 1: dose-normalized Cmax and AUClast for PF05221304(0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose)
- Part 1: Plasma Decay Half-Life (t1/2) for PF-05221304 (as permitted)(0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose)
- Part 2: Single dose plasma parameters of Cmax for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Day 1)
- Part 2: Single-dose plasma parameters of Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Day 1)
- Part 2: Multiple-dose plasma parameters of Cmax for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted))
- Part 2: Multiple-dose plasma parameters of Minimum Observed Plasma Trough Concentration (Cmin) for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted))
- Part 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05221304(0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, and 48 hours post dose)
- Part 2: Multiple-dose plasma parameters of Observed accumulation ratio for Cmax (Rac(Cmax)) for PF-05221304(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post dose for Day 7; (and Day 14, as permitted))
- Part 3: Number of Subjects experiencing an Adverse Event(Screening up to 28 days after last dose of study medication)
- Part 2: Multiple-dose plasma parameters of Vz/F for PF-05221304 (as permitted)(0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours on Day 1 and 7, and 0 hr on Day 2, Day 4, Day 8, Day 10, Day 13, Day 15, and Day 16 post dose)