Clinical trial NCT04802863: Intrapulmonary Pharmacokinetics of XNW4107, Imipenem and Cilastatin in Healthy Subjects
Official title: A Phase 1, Open-label Study to Evaluate the Safety and Intrapulmonary Pharmacokinetics of XNW4107, Imipenem and Cilastatin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bacterial Infections
Lead sponsor: Evopoint Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-17
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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;

Primary outcomes:
measure: 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.
timeFrame: From baseline to 12 hours post- fifth dose
measure: AUC extrapolated to infinity (AUC0-∞) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
timeFrame: From baseline to 12 hours post- fifth dose
measure: 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.
timeFrame: From baseline to 6 hours post- fifth dose
measure: Maximum concentration (Cmax) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
timeFrame: From baseline to 12 hours post- fifth dose
measure: Minimum concentration (Cmin) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
timeFrame: From baseline to 12 hours post- fifth dose
measure: Time to Cmax (tmax) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
timeFrame: From baseline to 12 hours post- fifth dose
measure: The terminal-phase half-life (t1/2) of plasma PK and lung penetration of XNW4107, imipenem and cilastatin in healthy adult volunteers.
timeFrame: From baseline to 12 hours post- fifth dose
Secondary outcomes:
measure: Number of participants with treatment-related adverse events of Hematology as assessed by CTCAE v5.0
timeFrame: From baseline up to Day 9
measure: Number of participants with treatment-related adverse events of Coagulation as assessed by CTCAE v5.0.
timeFrame: From baseline up to Day 9
measure: Number of participants with treatment-related adverse events of Biochemistry as assessed by CTCAE v5.0.
timeFrame: From baseline up to Day 9
measure: Number of participants with treatment-related adverse events of Urinalysis as assessed by CTCAE v5.0.
timeFrame: From baseline up to Day 9
measure: Number of participants with treatment-related adverse events of Physical Examination as assessed by CTCAE v5.0.
timeFrame: From baseline up to Day 9
measure: Number of participants with treatment-related adverse events of Vital Signs as assessed by CTCAE v5.0.
timeFrame: From baseline up to Day 9
measure: Number of participants with treatment-related adverse events of 12-Lead Electrocardiogram (ECG) as assessed by CTCAE v5.0.
timeFrame: From baseline up to Day 9
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates PA
state: Arizona
Study officials:
References: