A Double Blind, 3rd Party Open, Placebo Controlled, Dose Escalating, Parallel Study To Investigate The Safety, Toleration And Pharmacokinetics Of Multiple Oral Doses Of PF-04634817 In Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Adverse events, supine and standing vital sign measurements, 12-lead ECGs, blood and urine safety tests.
研究概览
简要总结
The goals of this study are to evaluate the safety and tolerability of multiple ascending doses of PF-04634817 administered orally to healthy adult subjects. In additional, the plasma and urinary pharmacokinetics of multiple ascending doses of PF-04634817 administered orally to healthy adult subjects will be evaluated. Finally, the effect of multiple doses of PF-04634817 on circulating monocytes will be explored.
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 female (of non-childbearing potential) subjects between the ages of 18 and 55 years, inclusive.
- •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
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease;
- •Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication;
- •Use of tobacco- or nicotine-containing products in excess of the equivalent of 5 cigarettes per day;
- •Nursing females;
- •Females of childbearing potential.
研究组 & 干预措施
Cohort 1 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 3 mg per day for 14 days. (2 placebo: 8 active)
干预措施: PF-04634817 (Drug)
Cohort 2 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 3 mg per day for 14 days. (2 placebo: 8 active)
干预措施: PF-04634817 (Drug)
Cohort 3 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 30 mg per day for 14 days. (2 placebo: 8 active)
干预措施: PF-04634817 (Drug)
Cohort 4 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 100 mg per day for 14 days. (2 placebo: 8 active)
干预措施: PF-04634817 (Drug)
Cohort 5 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 300 mg per day for 14 days. (2 placebo: 8 active)
干预措施: PF-04634817 (Drug)
Cohort 6 (N=10) Optional cohort
Placebo-controlled, multiple doses of PF-04634817 up to 300 mg per day for 14 days. (2 placebo: 8 active)
干预措施: PF-04634817 (Drug)
结局指标
主要结局
Adverse events, supine and standing vital sign measurements, 12-lead ECGs, blood and urine safety tests.
时间窗: 14 days
Plasma PK Day 1: Cmax, Tmax, AUClast, AUCtau at all dose levels. Plasma PK Day 14: Cmax, Tmax, AUClast, AUCtau, AUCinf, t½, CL/F and Vss/F at all dose levels.
时间窗: 14 days
AUCtau (Day 14) vs. AUCtau (Day 1) - estimate of accumulation ratio; Cmax (Day 14) vs. Cmax (Day 1); Tmax (Day 14) vs. Tmax (Day 1).
时间窗: 14 days
Urinary PK: Aet (amount excreted in urine); Aet% at all doses of PF-04634817 where t = 24 hours on Day 1 and 14; CLr at all doses on Day 14.
时间窗: 14 days
Pharmacodynamic: MCP-1 change from baseline.
时间窗: 14 days
次要结局
- Pharmacodynamic: p-ERK Inhibition in human monocytes: percent inhibition of monocyte p-ERK activity relative to the pre-dose baseline value(14 days)
- MIP-1β stimulated CCR5 receptor internalization: percent inhibition of internalization relative to the pre-dose baseline value(14 days)
- Absolute and percent change in circulating monocytes; Absolute and percent change in CD14+CD16+ monocytes.(14 days)