Intrapulmonary Pharmacokinetics of XNW4107, Imipenem and Cilastatin in Healthy Subjects

NCT ID: NCT04802863

Last Updated: 2023-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-25
• Study Completion Date: 2021-09-30

Brief Summary

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

Conditions

Bacterial Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Five doses of XNW4107 with imipenem/cilastatin

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.

Group Type: EXPERIMENTAL

XNW4107, Imipenem/Cilastatin

Intervention Type: DRUG

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

Interventions

XNW4107, Imipenem/Cilastatin

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

Intervention Type: DRUG

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Evopoint Biosciences Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pulmonary Associates PA

Phoenix, Arizona, United States

Countries

United States

Other Identifiers

XNW4107-004

Identifier Type: -

Identifier Source: org_study_id