A Phase 1, Randomized, Single-center, Double-blind, Placebo-controlled Study of Fosmanogepix Administered as Single and Multiple Doses in Healthy Adult Chinese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Manogepix in Part-1
研究概览
简要总结
The purpose of this study was to investigate the pharmacokinetics and safety of the investigational drug fosmanogepix including its active moiety manogepix following a single dose and multiple doses (by intravenous infusion (IV) or orally) in healthy Chinese adults.
The study consisted of 2 consecutive Parts (Part-1, single-dose part followed by Part-2, multiple-dose part) including a total of 54 subjects (32 subjects in Part-1 and 22 subjects in PART-2) randomized.
详细描述
Part-1 duration including screening period was up to 64 days including 4 visits at the clinical site and Part-2 duration including screening period was up to 70 days including 5 visits at the clinical site. The study included a total of 4 study sub-groups (Cohorts 1-4) in which fosmanogepix or placebo was administered in different strengths orally or IV.
Subjects were enrolled and randomly assigned to study drug.
During the study, serial blood samples were collected to understand how fosmanogepix was changed and eliminated from the body.
The primary objective of PART-1 (Single-dose) was to evaluate the pharmacokinetic (PK) profile of manogepix (active moiety of fosmanogepix) after single dose administration in healthy adult Chinese subjects.
The primary objective of PART-2 (Multiple-dose) was to evaluate the PK profile of manogepix (active moiety of fosmanogepix) after repeated doses in healthy adult Chinese subjects.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Main criteria for inclusion and exclusion:
- •Body mass index (BMI) of 18.0 to 30.0 kg/m2 inclusive, and a total body weight > 45 kg for females and > 50 kg for males at Screening.
- •Subjects who were overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, vital signs, creatinine, and estimated creatinine clearance (Cockcroft-Gault formula).
排除标准
- •Active acute or chronic infection, including, but not limited to upper airway infection, urinary tract infection, or skin infection at Screening.
- •Any condition possibly affecting drug absorption.
- •Medical history of neurological disorders including abnormal movements or seizures.
- •Use of prescription or non-prescription drugs, including vaccines, and dietary and herbal supplements from Screening or within five half-lives (whichever is longer) prior to the first dose of study drug and throughout the study.
- •Screening supine blood pressure (BP) ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic), and pulse rate (PR) > 100 beats per minute (bpm) or < 50 bpm, following at least 5 minutes of supine rest.
- •Body temperature higher than 37.5 °C.
- •Screening supine 12 lead ECG demonstrating clinically relevant abnormalities that may affect subject safety or interpretation of study results.
- •Subjects with any of the following abnormalities in clinical laboratory tests at Screening, as assessed by the local laboratory and confirmed by a single repeat test, if deemed necessary:
- •AST or ALT ≥ 1.0 × ULN.
- •Total bilirubin ≥ 1.5 × ULN.
研究组 & 干预措施
Single-dose Part -1 (Cohort 1, oral)
Subjects received fosmanogepix or placebo by oral administration
干预措施: Oral Fosmanogepix (Drug)
Single-dose Part -1 (Cohort 1, oral)
Subjects received fosmanogepix or placebo by oral administration
干预措施: oral placebo (Drug)
Single-dose Part-1 (Cohort 2, IV)
Subjects received fosmanogepix or placebo by IV infusion
干预措施: IV Fosmanogepix (Drug)
Multiple-dose Part-2 (Cohort 3, IV)
Subjects received fosmanogepix or placebo as an IV infusion twice 12 hours apart on Day 1 followed by a maintenance daily dose of fosmanogepix or placebo via IV infusion from Day 2 to Day 7
干预措施: IV Fosmanogepix (Drug)
Multiple-dose Part-2 (Cohort 3, IV)
Subjects received fosmanogepix or placebo as an IV infusion twice 12 hours apart on Day 1 followed by a maintenance daily dose of fosmanogepix or placebo via IV infusion from Day 2 to Day 7
干预措施: IV placebo (Drug)
Single-dose Part-1 (Cohort 2, IV)
Subjects received fosmanogepix or placebo by IV infusion
干预措施: IV placebo (Drug)
Multiple-dose Part-2 (Cohort 4, IV followed by oral)
The subjects received fosmanogepix or placebo as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7.
干预措施: Oral Fosmanogepix (Drug)
Multiple-dose Part-2 (Cohort 4, IV followed by oral)
The subjects received fosmanogepix or placebo as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7.
干预措施: IV Fosmanogepix (Drug)
Multiple-dose Part-2 (Cohort 4, IV followed by oral)
The subjects received fosmanogepix or placebo as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7.
干预措施: IV placebo (Drug)
Multiple-dose Part-2 (Cohort 4, IV followed by oral)
The subjects received fosmanogepix or placebo as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7.
干预措施: oral placebo (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Manogepix in Part-1
时间窗: pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240 hours postdose
Pharmacokinetic (PK) parameter Cmax for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects
Time to Peak Manogepix Concentration (Tmax) of Manogepix in Part-1
时间窗: pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240 hours postdose
PK parameter Tmax for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects
Area Under the Plasma Concentration vs. Time Curve for 0-24 Hours (AUC24) of Manogepix in Part-1
时间窗: pre-dose, 1, 2, 3, 4, 6, 8, 12, 24 hours postdose
PK parameter AUC 24 for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Manogepix in Part-1
时间窗: pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240 hours postdose
PK parameter AUClast for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Manogepix in Part-1
时间窗: pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240 hours postdose
PK parameter AUC (0 - ∞) for manogepix after a single oral administration of 400 mg or 800 mg fosmanogepix or after a single IV infusion of 600 mg or 1,000 mg fosmanogepix over 3 hours to healthy Chinese subjects
Maximum Observed Plasma Concentration (Cmax) of Manogepix in Part-2
时间窗: pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240, 360 hours postdose on Day 7
PK parameter Cmax after fosmanogepix administration as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose from Day 2 to Day 7 or followed by an IV maintenance dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7
Time to Peak Manogepix Concentration (Tmax) of Manogepix in Part-2
时间窗: pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240, 360 hours postdose on Day 7
PK parameter Tmax after fosmanogepix administration as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7
Area Under the Concentration-time Curve at Steady State Over the Dosing Interval Tau (AUCtau) of Manogepix in Part-2
时间窗: pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 240, 360 hours postdose on Day 7
PK parameter AUCtau after fosmanogepix administration as an IV infusion twice 12 hours apart on Day 1 followed by an IV maintenance daily dose from Day 2 to Day 7 or followed by an IV maintenance dose on Day 2 and Day 3, and then switched to oral administration (of fosmanogepix or placebo) daily from Day 4 to Day 7
次要结局
- Fraction of Unbound Manogepix in Plasma in Part 1(pre-dose and 3 hours postdose)
- Number of Subjects With Treatment-emergent AE (TEAE) in Part-1(Up to 36 days)
- Number of Subjects With TEAE in Part-2(Up to 42 days)