A Phase 1, Open-label Study to Evaluate the Safety and Intrapulmonary Pharmacokinetics of XNW4107, Imipenem and Cilastatin in Healthy Subjects

XNW4107-004

This is a Phase 1, open-label, single-center study of XNW4107 and imipenem/cilastatin administered intravenously.

2021-03-25

2021-05-15

2021-09-30

Completed

Early phase I

21

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;

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 21, 'type': 'ACTUAL'}}

2023-02-16