A Phase 1, Single-Dose, Randomized, Double Blind, Placebo-Controlled Study to Evaluate Pharmacokinetics, Safety and Tolerability of XNW4107 for Injection in Healthy Adult Young Females and in Healthy Adult Elderly Males and Females.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- (Plasma) Maximum plasma concentration (Cmax) of of XNW4107, imipenem and cilastatin.
研究概览
简要总结
This is a Phase 1, randomized, double-blind, placebo-controlled study to assess the PK, safety and tolerability of XNW4107, imipenem and cilastatin administered by 60-min (± 3 min) IV infusion in healthy adult young females and in healthy adult elderly males and females.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult female, 18 to 45 years of age (both inclusive) or 65 years or over (≥ 65 years); or healthy adult male 65 years or over (≥ 65 years).
- •BMI ≥ 18.0 and ≤ 32.0 (kg/m²) and weight between 55.0 and 100.0 kg (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 and urinalysis.
- •Male or female, willing to contracept. If female, must be non-pregnant and non-lactating.
- •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 48 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.
- •Electrocardiogram (ECG) with QTcF interval duration equal or greater than 450 msec for males and 470 msec for females obtained after at least 5 minutes 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: • White blood cell count < 3,000/mm³, hemoglobin < 11g/dL; • Absolute neutrophil count <1,200/mm³, platelet count <120,000/mm³; • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 1.5 x the upper limit of normal (ULN) for the reference laboratory.
- •History of seizure disorder except childhood history of febrile seizures.
- •Positive 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.
- •Recent history (within 6 months) of known or suspected Clostridium difficile infection.
- •Positive testing for HIV Ab, HBsAg or HCV Ab.
- •9.Positive urine drug or alcohol testing at screening or check-in (Day -1).
- •10.Use of prescription medications (with the exception of hormone replacement therapy and contraceptives), 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).
- •Receipt of an investigational drug within 30 days or 5 half-lives prior to the first administration of study drug, whichever is longer.
- •Known history of clinically significant hypersensitivity reaction or anaphylaxis to any medication, or history of clinically significant hypersensitivity to the study drug or any related drugs or to any of the excipients, or significant food intolerance.
- •Donation of blood or plasma within 30 days prior to dosing, or loss of whole blood of more than 500 mL within 30 days prior to dosing, or receipt of a blood transfusion within 1 year of study enrollment.
- •Any other condition or prior therapy, which, in the opinion of the Investigator, would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.
研究组 & 干预措施
Cohort 1: Healthy young females
Healthy young females participants, ≥ 18 to ≤ 45 years of age, randomized to receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg.
干预措施: XNW4107 (Drug)
Cohort 1: Healthy young females
Healthy young females participants, ≥ 18 to ≤ 45 years of age, randomized to receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg.
干预措施: Imipenem/Cilastatin (Drug)
Cohort 2: Healthy elderly males
Healthy elderly male participants, ≥ 65 years of age, randomized to receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg.
干预措施: XNW4107 (Drug)
Cohort 2: Healthy elderly males
Healthy elderly male participants, ≥ 65 years of age, randomized to receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg.
干预措施: Imipenem/Cilastatin (Drug)
Cohort 3: Healthy elderly females
Healthy elderly female participants, ≥ 65 years of age, randomized to receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg.
干预措施: XNW4107 (Drug)
Cohort 3: Healthy elderly females
Healthy elderly female participants, ≥ 65 years of age, randomized to receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg.
干预措施: Imipenem/Cilastatin (Drug)
Placebo to XNW 4107 & imipenem/cilastatin
Matching placebo for XNW4107 and imipenem/cilastatin
干预措施: placebo (Drug)
结局指标
主要结局
(Plasma) Maximum plasma concentration (Cmax) of of XNW4107, imipenem and cilastatin.
时间窗: From baseline to 48 hours post-dose
(Plasma)Total body clearance (CL/F) of of XNW4107, imipenem and cilastatin.
时间窗: From baseline to 48 hours post-dose
(Plasma) AUC extrapolated to infinity (AUC0-∞) of of XNW4107, imipenem and cilastatin.
时间窗: From baseline to 48 hours post-dose
(Plasma) Time to the maximum plasma concentration (Tmax) of of XNW4107, imipenem and cilastatin.
时间窗: From baseline to 48 hours post-dose
(Urine) Renal clearance (CLR) of the XNW4107, imipenem and cilastatin dose administered.
时间窗: From baseline to 48 hours post-dose
(Plasma) Area under the curve from time zero to the last quantifiable sample (AUC0-last) of XNW4107, imipenem and cilastatin.
时间窗: From baseline to 48 hours post-dose
(Plasma) Apparent steady-state volume of distribution (Vss/F) of of XNW4107, imipenem and cilastatin.
时间窗: From baseline to 48 hours post-dose
(Plasma) The terminal elimination half-life (t1/2) of XNW4107, imipenem and cilastatin.
时间窗: From baseline to 48 hours post-dose
(Urine) Amount of drug excreted in the urine through 24 hours (Ae0-24)
时间窗: From baseline to 24 hours post-dose
(Urine) Amount of drug excreted in the urine through 48 hours (Ae0-48)
时间窗: From baseline to 48 hours post-dose
(Urine) Fraction of drug excreted in the urine expressed as a percentage of the XNW4107, imipenem and cilastatin dose administered (Ae%)
时间窗: From baseline to 48 hours post-dose
次要结局
- Number of participants with treatment-related adverse events of Coagulation as assessed by CTCAE v5.0.(From baseline up to 10 days post-dose)
- Number of participants with treatment-related adverse events of Urinalysis as assessed by CTCAE v5.0.(From baseline up to 10 days post-dose)
- Number of participants with treatment-related adverse events of Hematology as assessed by CTCAE v5.0(From baseline up to 10 days post-dose)
- Number of participants with treatment-related adverse events of Vital Signs as assessed by CTCAE v5.0.(From baseline up to 10 days post-dose)
- Number of participants with treatment-related adverse events of Physical Examination as assessed by CTCAE v5.0.(From baseline up to 10 days post-dose)
- Number of participants with treatment-related adverse events of Biochemistry as assessed by CTCAE v5.0.(From baseline up to 10 days post-dose)
- Number of participants with treatment-related adverse events of 12-Lead Electrocardiogram (ECG) as assessed by CTCAE v5.0.(From baseline up to 3 days post-dose)