Study to Evaluate Safety, Tolerability, and Pharmacokinetics of XNW4107 Alone or in Combination With Imipenem/Cilastatin

NCT04482569 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: XNW4107-001
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 3-part, first-in-human study to evaluate the safety, tolerability and pharmacokinetics of escalating doses of XNW4107 given as intravenous (IV) infusion in healthy male subjects. In part 1, subjects will receive a single dose of XNW4107. In part 2, subjects will receive XNW4107 for 7 days. In Part 3, subjects will receive XNW4107 in combination with imipenem/cilastatin for 14 days.

Conditions

Bacterial Infections

Keywords

XNW4107; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Safety as assessed by number of participants experiencing adverse events

  Number of participants who experience adverse events in different grades, as defined by Common Terminology for Adverse Events (CTCAE) v5.0

  Change from baseline up to day 43 post-intervention

Study Arms (3)

Single Ascending Dose Study

EXPERIMENTAL

Six XNW4107 doses ( 50-1250 mg ), each administered as a single dose with 60-minute IV infusion

Drug: XNW4107

Multiple Ascending Dose Study

EXPERIMENTAL

Three XNW4107 doses (167-500 mg), each administered as 60-minute IV infusion every 6 hours for 7 days

Drug: XNW4107

Multiple Dose Study of XNW4107 +Imipenem/Cilastatin

EXPERIMENTAL

500 mg XNW4107 co-administered with imipenem/cilastatin as 60-minute IV infusion every 6 hours for 14 days

Drug: XNW4107

Interventions

XNW4107 DRUG

Single or multiple dose ascending study for XNW4107 alone or multiple dose study of XNW4107 in combination with imipenem/cilastatin

Multiple Ascending Dose Study; Multiple Dose Study of XNW4107 +Imipenem/Cilastatin; Single Ascending Dose Study

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male adults aged 18-65 years
• Body Mass Index (BMI) between 18.5 - 32.0, inclusive.
• In good general health, as determined by the Investigator, based on medical history, physical examination, 12 lead electrocardiogram (ECG), vital sign (VS) measurements, and laboratory test results.
• Normal blood pressure (BP), defined as: systolic BP (SBP) ≥90 mmHg and ≤140 mmHg; and diastolic BP (DBP) \<90 mmHg at the time of Screening
• Male subjects with female partners of reproductive potential must agree to practice abstinence or to use a condom (male subject) in addition to an acceptable method (female partner) of contraception for the duration of the study and for at least 90 days post last dose.
• Negative serology results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), human immunodeficiency virus antibody (HIV Ab), hepatitis E immunoglobulin M antibody (IgM anti HEV), and Treponema pallidum antibody chemiluminescent immunoassay (TP IA).
• Negative serology results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), human immunodeficiency virus antibody (HIV Ab), hepatitis E immunoglobulin M antibody (IgM anti HEV), and Treponema pallidum antibody chemiluminescent immunoassay (TP IA).
• Non smoker (with no use of other tobacco or nicotine containing products, in any form), as documented by history (no nicotine within 3 months prior to Screening)
• Negative results for drugs of abuse, alcohol, and cotinine at Screening and Admission

You may not qualify if:

• History of clinically significant psychiatric disorder within the past 5 years.
• History of stroke, chronic seizures, or other major neurological disorder.
• History or evidence of drug/alcohol abuse within 1 year prior to Screening.
• History of clinically significant endocrine, neurological, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or disease.
• History of cancer (malignancy).
• History of any illness that, in the opinion of the study investigator, may confound the results of the study or pose additional risk to the subject if he participates in the study.
• Administration of another investigational medication within 30 days (or 5 half lives, whichever is longer) prior to study drug administration.
• Participation in an investigational device study within 30 days prior to study drug administration.
• Excessive consumption of alcohol, defined as \>3 alcoholic beverages per day (10 ounces of beer \[284 mL\], 4 ounces of wine \[125 mL\], or 1 ounce of distilled spirits \[25 mL\] is approximately equivalent to 1 alcoholic beverage)
• Excessive consumption of coffee, tea, cola, or other caffeinated beverages; excessive consumption is defined as \>6 servings per day (1 serving contains approximately 120 mg caffeine)
• History and/or family history of congenital long QT syndrome, unexplained syncope, or other additional risks of Torsade de Pointes or sudden premature death.
• Any ECG abnormality considered to be clinically significant by the principal investigator (PI)/designee;
• Glomerular filtration rate (GFR) ≤80 mL/min/1.73 m2, as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation.
• Ongoing liver disease or unexplained liver function test (LFT) elevations
• History of hypersensitivity to β lactam antibiotics (including, but not limited to imipenem)

Sponsors & Collaborators

• Evopoint Biosciences Inc.: lead

Study Sites (1)

Pharmaron CPC

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Bacterial Infections

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Officials

• Jason Le

  Evopoint Biosciences Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2020
• First Posted: July 22, 2020
• Study Start: July 10, 2020
• Primary Completion: February 28, 2021
• Study Completion: September 30, 2021
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

US (1)