A Phase 1, Open-label Study to Evaluate the Safety and Intrapulmonary Pharmacokinetics of XNW4107, Imipenem and Cilastatin in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Area under the concentration curve (AUC) from time zero to the last quantifiable sample (AUC0-t) of plasma PK and lung penetration of XNW4107, imipenem and cilastatine in healthy adult volunteers.
研究概览
简要总结
This is a Phase 1, open-label, single-center study of XNW4107 and imipenem/cilastatin administered intravenously.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
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
- •1． Adult males or female subjects, between 18 and 55 years of age (both inclusive) at the time of screening;
- •BMI ≥ 18.5 and ≤ 32 (kg/m²) and weight between 55.0 and 100.0 kg (both inclusive);
- •Medically healthy without clinically significant abnormalities as assessed by the Investigator based on screening medical history, physical examination, vital signs, 12-lead ECG, hematology, biochemistry, coagulation and urinalysis;
- •Forced expiratory volume in 1 second (FEV1) of at least 80% of predicted value at screening;
- •Non-smoker (with no use of other tobacco, nicotine or marijuana-containing products, in any form), as documented by history (no nicotine or marijuana use within 3 months prior to Screening);
- •Negative urine drug, alcohol or cotinine testing at screening and check-in (Day -1);
- •Participants of reproductive potential (male or female) must be willing to use contraception
- •Ability and willingness to abstain from alcohol, caffeine, xanthine-containing beverages or food (coffee, tea, chocolate, and caffeine-containing sodas, colas, etc.) or product containing any of these from 72 hours prior to study drug administration until discharge from the clinical unit.
排除标准
- •History or presence of significant oncologic, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, vascular or neurological disease, including any acute illness or surgery within the past 3 months determined by the Investigator to be clinically relevant;
- •Recent history (within 6 months) of known or suspected Clostridium difficile infection;
- •History of seizure disorder;
- •Positive testing for human immunodeficiency virus antibody (HIV Ab), hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV Ab);
- •Positive RT-PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening;
- •Close contact with anyone who tested positive for SARS-CoV-2 infection, or presence of symptoms associated with SARS-CoV-2 infection at Screening or Check-in, or within 14 days prior to Screening.
- •Electrocardiogram (ECG) with QTcF interval duration equal or greater than 450 msec for males and 470 msec for females obtained after at least 5 min in a supine or semi-supine position at quiet rest at Screening or Check-In (Day -1);
- •Subjects who have any of the following abnormalities on laboratory values at screening or prior confinement including: a. White blood cell count < 3,000/mm³, hemoglobin < 11g/dL; b. Absolute neutrophil count <1,200/mm³, platelet count <120,000/mm³; c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 1.5 x the upper limit of normal (ULN) for the reference laboratory;
- •History of substance abuse or alcohol abuse within the previous 5 years;
- •Use of prescription medications (with the exception of hormone replacement therapy and contraceptives listed in inclusion criterion #10), including nonsteroidal anti-inflammatory drugs, sucralfate, or herbal preparations within 7 days before Check in (Day -1), or use of an over-the-counter medication, acetaminophen (>2 g/day), vitamins, or supplements (including fish liver oils) within 7 days before Check in (Day -1); or probenecid or valproic acid within 30 days before Check in (Day -1);
- •History of hypersensitivity to β-lactam antibiotics or drugs that include sulfobutylether β-cyclodextrin sodium (SBECD) as an excipient (e.g. Tegretol, Vfend, Geodon and Noxafil);
- •History of significant multiple and/or severe allergies (including latex allergy); anaphylactic reaction; or significant prescription drug, non-prescription drug, or food intolerance.
- •Donation of blood or plasma within 30 days prior to Check-In (Day-1), or loss of whole blood of more than 500 mL within 30 days prior to Check-In (Day-1), or receipt of a blood transfusion within 1 year of study enrollment;
- •Participation in another investigational clinical trial within 30 days prior to screening;
- •A female who is pregnant or breastfeeding;
研究组 & 干预措施
Five doses of XNW4107 with imipenem/cilastatin
Each subject will receive a total of five doses of 250 mg XNW4107 in combination with 500 mg imipenem/500 mg cilastatin via IV infusion administered every 6 hours with each administration infused over 60 minutes.
干预措施: XNW4107, Imipenem/Cilastatin (Drug)
结局指标
主要结局
Area under the concentration curve (AUC) from time zero to the last quantifiable sample (AUC0-t) of plasma PK and lung penetration of XNW4107, imipenem and cilastatine in healthy adult volunteers.
时间窗: From baseline to 12 hours post- fifth dose
AUC extrapolated to infinity (AUC0-∞) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
时间窗: From baseline to 12 hours post- fifth dose
AUC from time zero to 6 hours after start of the infusion (AUC0-6) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
时间窗: From baseline to 6 hours post- fifth dose
Maximum concentration (Cmax) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
时间窗: From baseline to 12 hours post- fifth dose
Minimum concentration (Cmin) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
时间窗: From baseline to 12 hours post- fifth dose
Time to Cmax (tmax) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
时间窗: From baseline to 12 hours post- fifth dose
The terminal-phase half-life (t1/2) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
时间窗: From baseline to 12 hours post- fifth dose
次要结局
- Number of participants with treatment-related adverse events of Hematology as assessed by CTCAE v5.0(From baseline up to Day 9)
- Number of participants with treatment-related adverse events of Coagulation as assessed by CTCAE v5.0.(From baseline up to Day 9)
- Number of participants with treatment-related adverse events of Biochemistry as assessed by CTCAE v5.0.(From baseline up to Day 9)
- Number of participants with treatment-related adverse events of Urinalysis as assessed by CTCAE v5.0.(From baseline up to Day 9)
- Number of participants with treatment-related adverse events of Physical Examination as assessed by CTCAE v5.0.(From baseline up to Day 9)
- Number of participants with treatment-related adverse events of Vital Signs as assessed by CTCAE v5.0.(From baseline up to Day 9)
- Number of participants with treatment-related adverse events of 12-Lead Electrocardiogram (ECG) as assessed by CTCAE v5.0.(From baseline up to Day 9)