Intrapulmonary Pharmacokinetics of XNW4107, Imipenem and Cilastatin in Healthy Subjects

NCT04802863 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: XNW4107-004
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Bacterial Infections

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  From baseline to 12 hours post- fifth dose

Secondary Outcomes (7)

• 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

Study Arms (1)

Five doses of XNW4107 with imipenem/cilastatin

EXPERIMENTAL

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.

Drug: XNW4107, Imipenem/Cilastatin

Interventions

XNW4107, Imipenem/Cilastatin DRUG

Five doses of 250 mg XNW4107 in combination with 500 mg imipenem/500 mg cilastatin

Five doses of XNW4107 with imipenem/cilastatin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• ． 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.

You may not qualify if:

• \. 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;
• \. 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;

Sponsors & Collaborators

• Evopoint Biosciences Inc.: lead

Study Sites (1)

Pulmonary Associates PA

Phoenix, Arizona, 85032, United States

Location

MeSH Terms

Conditions

Bacterial Infections

Interventions

Imipenem; Cilastatin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 17, 2021
• Study Start: March 25, 2021
• Primary Completion: May 15, 2021
• Study Completion: September 30, 2021
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)