Pharmacokinetics of XNW4107 in Subjects With Various Degrees of Renal Function

NCT04787562 | Completed Phase 1 FDA Drug

• 1 other identifier: XNW4107-003
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1, open-label study to assess the PK, safety and tolerability of XNW4107, imipenem and cilastatin administered by 60-minute (60-min) IV infusion to adults with various degrees of renal insufficiency as compared to subjects with normal renal function.

Conditions

Bacterial Infections

Outcome Measures

Primary Outcomes (6)

• Total body clearance (CL) of XNW4107, imipenem and cilastatin in subjects with various of Renal function.

  From baseline to 48 hours post-dose

• Apparent steady-state volume of distribution (Vss) of XNW4107, imipenem and cilastatin in subjects with various of Renal function.

  From baseline to 48 hours post-dose

• Area under the curve from time zero to infinity (AUC0-∞)of XNW4107, imipenem and cilastatin in subjects with various of Renal function.

  From baseline to 48 hours post-dose

• Maximum plasma concentration (Cmax) of XNW4107, imipenem and cilastatin in subjects with various of Renal function.

  From baseline to 48 hours post-dose

• Time to the maximum plasma concentration (Tmax) of XNW4107, imipenem and cilastatin in subjects with various of Renal function.

  From baseline to 48 hours post-dose

• The terminal elimination half-life (t1/2) of XNW4107, imipenem and cilastatin in subjects with various of Renal function.

  From baseline to 48 hours post-dose

Secondary Outcomes (1)

• Adverse event (include SAEs) will be assessed and categorized.

  From baseline up to 10 days post-dose

Study Arms (5)

Cohort 1: normal renal function

EXPERIMENTAL

Participants with an eGFR ≥ 90 mL/min/1.73m2 receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg

Drug: XNW4107, Imipenem/Cilastatin

Cohort 2: Mild renal insufficiency

EXPERIMENTAL

Participants with an eGFR 60 to \<90 mL/min/1.73m2 receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg

Drug: XNW4107, Imipenem/Cilastatin

Cohort 3: Moderate renal insufficiency

EXPERIMENTAL

Participants with an eGFR 30 to \<60 mL/min/1.73m2 receive a single dose of XNW4107 250mg IV co-administered with imipenem 500mg /cilastatin 500mg

Drug: XNW4107, Imipenem/Cilastatin

Cohort 4: Severe renal insufficiency

EXPERIMENTAL

Participants with an eGFR 15 to \<30 mL/min/1.73m2 receive a single dose of XNW4107 100mg IV co-administered with imipenem 200mg /cilastatin 200mg

Drug: XNW4107, Imipenem/Cilastatin

Cohort 5: End-stage renal disease (ESRD) receiving hemodialysis (HD) therapy

EXPERIMENTAL

Participants with ESRD receiving HD therapy at least 3 times a week for at least 3 months prior to Screening visit receive a single dose of XNW4107 100mg IV co-administered with imipenem 200mg /cilastatin 200mg

Drug: XNW4107, Imipenem/Cilastatin

Interventions

XNW4107, Imipenem/Cilastatin DRUG

Drug: XNW4107 250mg IV over 60 minutes as a single dose Drug: Imipenem/Cilastatin 500mg/500mg IV over 60 minutes as a single dose

Cohort 1: normal renal function

Eligibility Criteria

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

You may qualify if:

• \. Adult males or females, 18 years of age or older.
• \. BMI ≥ 18.5 and ≤ 39.9 (kg/m²) and weight between 50.0 and 130.0 kg (inclusive).
• \. Medically healthy (Cohort 1 only) or medically stable without clinically significant acute or chronic illness (Cohorts 2-5) that may impact the assessment of PK and safety.
• \. Normal renal function with eGFR ≥90 mL/min/1.73m² (Cohort 1), or renal insufficiency with eGFR 60 to \<90 mL/min/1.73m² (Cohort 2), 30 to \<60 mL/min/1.73m² (Cohort 3), or 15 to \<30 mL/min/1.73m² (Cohort 4), ESRD receiving HDs at least 3 times per week for at least 3 months at Screening (Cohort 5)
• \. 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 or product containing any of these from 48 hours prior to study drug administration until discharge from the clinical unit.

You may not qualify if:

• \. Any clinically significant medical history or abnormal findings upon physical examination, or clinical laboratory tests.
• \. Electrocardiogram (ECG) with QTcF interval duration equal or greater than 500 msec obtained at Screening or Check-In.
• \. Results for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin greater than 1.5 × the upper limit of normal (ULN) for the reference laboratory.
• \. History of chronic liver disease, cirrhosis, or biliary disease.
• \. History or presence of CNS disorders, seizures, or other CNS adverse reactions such as confusional states and myoclonic activity.
• \. Positive 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.
• \. Recent history (within 6 months) of known or suspected Clostridium difficile infection.
• \. Positive testing for HIV Ab, HBsAg or HCV Ab.
• \. Recent history of substance or alcohol abuse within the previous year, or habitual use of tobacco or nicotine products or smoking within 3 months prior to Screening.
• \. Positive drug screen and alcohol testing at Screening or Check-in.
• \. For subjects with normal renal function (Cohort 1), the use of any over-the-counter (OTC) medications within 7 days prior to study drug administration or use of prescription medications including nonsteroidal anti-inflammatory drugs, health supplements, and herbal remedies taken within 13 days prior to study drug administration.
• \. For subjects with renal impairment (Cohorts 2-5), the use of prohibited concomitant medication with the exception of those essential for the management of renal impairment and other concomitant stable medical conditions as per the discretion of the Investigator.
• \. Use of probenecid or valproic acid within 30 days prior to study drug administration.
• \. Receipt of an investigational drug within 30 days or 5 half-lives prior to the first administration of study drug, whichever is longer.

Sponsors & Collaborators

• Evopoint Biosciences Inc.: lead

Study Sites (2)

Division of Clinical Pharmacology (DCP), University of Miami

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center (OCRC)

Orlando, Florida, 32809-3017, 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 Officials

• Jason Le

  Evopoint Biosciences Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 8, 2021
• Study Start: February 25, 2021
• Primary Completion: October 30, 2021
• Study Completion: February 28, 2022
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)