intrapulmonary pharmacokinetics of xnw4107, imipenem and cilastatin in healthy subjects

Conditions: Bacterial Infections

Summary: this is a phase 1, open-label, single-center study of xnw4107 and imipenem/cilastatin administered intravenously.


Eligibility criteria:
inclusion criteria: * 1． adult males or female subjects, between 18 and 55 years of age (both inclusive) at the time of screening; 2. bmi ≥ 18.5 and ≤ 32 (kg/m²) and weight between 55.0 and 100.0 kg (both inclusive); 3. 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; 4. forced expiratory volume in 1 second (fev1) of at least 80% of predicted value at screening; 5. 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); 6. negative urine drug, alcohol or cotinine testing at screening and check-in (day -1); 7. participants of reproductive potential (male or female) must be willing to use contraception 8. 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. exclusion criteria: * 1. 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; 2. recent history (within 6 months) of known or suspected clostridium difficile infection; 3. history of seizure disorder; 4. positive testing for human immunodeficiency virus antibody (hiv ab), hepatitis b surface antigen (hbsag) or hepatitis c antibody (hcv ab); 5. positive rt-pcr testing for severe acute respiratory syndrome coronavirus 2 (sars-cov-2) at screening; 6. 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. 7. 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); 8. 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; 9. history of substance abuse or alcohol abuse within the previous 5 years; 10. 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); 11. 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); 12. history of significant multiple and/or severe allergies (including latex allergy); anaphylactic reaction; or significant prescription drug, non-prescription drug, or food intolerance. 13. 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; 14. participation in another investigational clinical trial within 30 days prior to screening; 15. a female who is pregnant or breastfeeding;