A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PNU-100480 (PF-02341272) After Administration Of Multiple Escalating Oral Doses To Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of ascending oral doses of PNU-100480 administered as extemporaneously prepared suspension (EPS) over 14 and 28 days in healthy adult volunteers.
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of multiple doses of PNU-100480 given for 14 or 28 days. Killing activity against the bacterium that causes tuberculosis (TB) will also be measured. The effect of adding an additional tuberculosis (TB) agent (given for 2 days) in addition to PNU-100480 will be evaluated. Linezolid open label to determine activity in whole blood assay (WBA).
详细描述
Evaluate safety, tolerability, pharmacokinetics and whole blood activity (WBA) of PNU-100480 given for 14 or 28 days; evaluate WBA of PNU with pyrazinamide; evaluate WBA of linezolid
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 adult volunteers willing and able to be confined to the Clinical Research Unit and comply with study schedule.
- •Women of non-childbearing potential only.
排除标准
- •History of hypersensitivity to, or intolerance of, linezolid.
- •Antibiotic treatment within 14 days prior to dosing, or any previous antibiotic use at the discretion of the investigator.
- •Previous history of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD).
研究组 & 干预措施
Cohort 1
干预措施: PNU-100480 (Drug)
Cohort 1
干预措施: Placebo (Drug)
Cohort 2
干预措施: PNU-100480 (Drug)
Cohort 2
干预措施: Placebo (Drug)
Cohort 3
干预措施: PNU-100480 (Drug)
Cohort 3
干预措施: Placebo (Drug)
Cohort 4
干预措施: PNU-100480 (Drug)
Cohort 4
干预措施: Placebo (Drug)
Cohort 5
干预措施: PNU-100480 (Drug)
Cohort 5
干预措施: Placebo (Drug)
Cohort 6 (optional)
干预措施: PNU-100480 (Drug)
Cohort 6 (optional)
干预措施: Placebo (Drug)
Linezolid Cohort
干预措施: Linezolid (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of ascending oral doses of PNU-100480 administered as extemporaneously prepared suspension (EPS) over 14 and 28 days in healthy adult volunteers.
时间窗: Monitor adverse events daily; safety eval pre-dose, specified times , discharge, follow-up/as needed
次要结局
- To characterize the single dose and steady state pharmacokinetics of ascending oral doses of PNU-100480 administered over 14 and 28 days in healthy adult volunteers with regard to the parent drug and its metabolites.(Full and sparse PK sampling from Day 1 through final day of dosing)
- To characterize the bactericidal activity in blood of orally administered PNU-100480 against intracellular M. tuberculosis in relation to blood concentrations ofPNU-100480 and its metabolites.(Full and sparse sampling from Day 1 through final day of dosing)
- To characterize the effect of once a day administration of pyrazinamide for 2 days on the pharmacokinetics and bactericidal activity in blood of orally administered PNU-100480 against intracellular M. tuberculosis (Cohorts 5 and 6, Days 27-28 only).(Days 27-28 as applicable)
- To characterize pharmacokinetics and bactericidal activity in blood of orally administered linezolid against intracellular M. tuberculosis following 4 days of QD dosing.(As applicable up to Day 4)