A Study to Investigate Safety and Pharmacokinetics of Intravenous Cefiderocol/Xeruborbactam in Participants With Renal Impairment

NCT ID: NCT07104162

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-16
• Study Completion Date: 2026-12-23

Brief Summary

A Phase 1, Open-label, Single-dose Study to Determine the Safety and Pharmacokinetics of Intravenous Cefiderocol/Xeruborbactam (S-649228) in Participants with Renal Impairment

Detailed Description

Qpex Biopharma, Inc., a wholly owned subsidiary of Shionogi Inc., is developing a fixed combination antibiotic of cefiderocol, a cephalosporin antibiotic approved in the US for the treatment of complicated urinary tract infections (cUTIs) including pyelonephritis, and hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), plus an investigational broad-spectrum beta-lactamase inhibitor (BLI), xeruborbactam (QPX7728) to address the need for new antibiotics for the pathogens deemed as urgent or critical threats.

The aim of this study is to compare single-dose intravenous (IV) pharmacokinetics (PK) and safety of the combination of cefiderocol/xeruborbactam (S-649228) in participants with various degrees of stable renal impairment, including those with end-stage renal disease (ESRD), to control participants with normal renal function.

The results from this study will enable the development of appropriate dosing recommendations in patients with impaired renal function.

Objectives:

The objectives of the study are:

1. To assess the impact of mild, moderate, and severe renal impairment, and intermittent hemodialysis (IHD) on the PK of IV cefiderocol and IV xeruborbactam given to participants with stable renal impairment, normal renal function, and ESRD receiving IHD therapy.

2. To evaluate the safety and tolerability of IV cefiderocol and IV xeruborbactam given to participants with stable renal impairment, normal renal function, and ESRD receiving IHD therapy.

Conditions

Bacterial Infections

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open Label, Single Dose of IV Cefiderocol/Xeruborbactam

Approximately 40 participants will be enrolled in total. Eight participants will be enrolled in each group (G) based on renal impairment (RI) determined by estimated glomerular function rate (eGFR) or need for intermittent hemodialysis (IHD) at screening:

• G1: Mild RI (eGFR 60 < 90 mL/min calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKP-EPI]) adjusted for the participant's body surface [BSA])
• G2: Moderate RI (eGFR 30 to < 60 mL/min calculated using the 2021 CKD-EPI equation adjusted for the participant's BSA)
• G3: Severe RI (eGFR < 30 mL/min calculated using the 2021 CKD-EPI equation) not receiving IHD therapy
• G4: Healthy participants with normal renal function matched to participants in Groups 1 and 2 (Group 3 may be included) based on age, gender and body mass index (BMI)
• G5: Participants with end stage renal disease (ESRD) receiving IHD

All participants will receive a single dose of cefiderocol/xeruborbactam on Day 1.

Group Type: EXPERIMENTAL

Cefiderocol/Xeruborbactam

Intervention Type: DRUG

A fixed dose combination of intravenous cefiderocol and intravenous xeruborbactam

Interventions

Cefiderocol/Xeruborbactam

A fixed dose combination of intravenous cefiderocol and intravenous xeruborbactam

Intervention Type: DRUG

Other Intervention Names

Cefiderocol/QPX7728; S-649228

Eligibility Criteria

Inclusion Criteria

An individual will be eligible to be included in the study only if all of the following criteria apply:

All participants

• Able to understand the study conduct and tasks required of the participants, sign the informed consent form and willing to cooperate with all tests and examinations required by the protocol.
• Aged 18 to 80 years, inclusive, at the time of consent.
• If male, agrees to be sexually abstinent or agrees to use 2 approved methods of contraception (refer to Inclusion Criterion 4) when engaging in heterosexual activity from Day -1 through 90 days following the last administration of the study intervention, and to not donate sperm during this same period of time. If the sexual partner is surgically sterile, contraception is not necessary.
• If female of childbearing potential, must either be sexually abstinent for 14 days prior to Day -1 and remain so through 30 days following dosing of the study intervention or have been using (or agree to use) 2 acceptable methods of birth control when engaging in heterosexual activity
• If female of childbearing potential, must agree not to donate eggs (ova, oocytes) for the purpose of reproduction from Day -1 through 30 days following the last administration of the study intervention.
• If female of non-childbearing potential, must either be postmenopausal (defined as 12 months spontaneous amenorrhea) with serum follicle stimulating hormone (FSH) level in the laboratory-defined postmenopausal range or have undergone sterilization procedures at least 6 months prior to Day -1; documentation of sterilization procedure must be obtained
• Has a BMI ≥ 18.5 kg/m2 and ≤ 45 kg/m2, inclusive.
• Has negative test results for hepatitis B surface antigen (HBsAg), anti-Hepatitis C virus (HCV) antibody, anti-human immunodeficiency virus (HIV) antibody, and SARS-CoV-2.

Participants with normal renal function:

• Has an eGFR ≥ 90 mL/min calculated using the 2021 CKD-EPI equation adjusted for the participant's BSA at screening
• Meets matching criteria for age, BMI, and gender of pooled renally impaired participants as defined in the protocol.

Participants with renal impairment

• Stable mild to severe renal impairment, as assessed by eGFR calculated using the 2021 CKD-EPI equation adjusted for the participant's BSA at screening
• Is on a stable medication regimen

Participants with ESRD on hemodialysis

• Receiving stable IHD at least 3 times a week for at least 3 months, using an arteriovenous fistula, graft, or catheter
• Is on a stable medication regimen

Exclusion Criteria

• Has unstable or new medical condition(s)
• Has had surgery under general anesthesia within the past 3 months prior to Day -1, determined by the investigator to be clinically relevant.
• Documented hypersensitivity reaction or anaphylaxis to any medication.
• History of seizures, convulsions
• Current evidence or history of malignancy
• If female, is pregnant, lactating, or has a positive pregnancy test at screening or Day -1.
• Received any investigational drug within 30 days or 5 half-lives, whichever is longer, of Day -1 for the current clinical study.
• Blood donation or significant blood loss (ie, > 500 mL) within 56 days prior to Day -1.
• Plasma or platelet donation within 14 days prior to Day -1.
• Any acute illness requiring antibiotic drug therapy within 30 days prior to Day -1 or a febrile illness within 7 days prior to Day -1.
• Vigorous exercise from 72 hours prior to Day -1 through the final FU/EOS Visit.
• Positive drug test at the Screening Visit or Day -1
• Positive alcohol test at screening or Day -1 and/or recent history (ie, within 6 months prior to Day -1) of excessive alcohol intake.
• Concurrent use of medications known to affect the elimination of serum creatinine and competitors of renal tubular secretion
• Employees of the investigative site involved in this study.
• Unable or unwilling to adhere to the study-specified procedures and restrictions.
• QTcF interval > 500 msec, previous history or family history of prolonged QT syndrome at screening or Day -1.
• Use of products containing alcohol, caffeine, xanthine, or ephedrine within 24 hours prior to Day -1; use of alcohol 48 hours prior to Day -1; use of proton pump inhibitors (eg, omeprazole and pantoprazole) 7 days prior to Day -1, including both over-the-counter (OTC) and prescription drugs in these categories; or consumption of grapefruit/grapefruit juice, Seville oranges, pomelo, exotic citrus fruits or grapefruit hybrids or juices containing such products within 7 days prior to Day -1.
• Has any clinically significant abnormalities in laboratory values at screening or Day -1, defined in the study protocol.

Participants with normal renal function:

• Abnormal and clinically significant findings on physical examination, medical history, serum chemistry, hematology, or urinalysis per Investigator discretion.

Participants with renal impairment, including those on IHD:

• Abnormal and clinically significant findings on physical examination, medical history, serum chemistry, hematology, or urinalysis per Investigator discretion. Participants in the renal impairment group will have consideration for the degree of renal impairment and presence of comorbidities.
• Has renal disease secondary to hepatic disease (hepatorenal syndrome)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Shionogi Inc.

INDUSTRY

Sponsor Role: collaborator

Biomedical Advanced Research and Development Authority

FED

Sponsor Role: collaborator

Qpex Biopharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Marbury, MD

Role: PRINCIPAL_INVESTIGATOR

Orlando Clinical Research Center

Richard Preston, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami Clinical Pharmacology

Miami, Florida, United States

Site Status: RECRUITING

Orlando Clinical Research Center

Orlando, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Grigor Mamikonyan, PharmD,PhD

Role: CONTACT

gmamikonyan@clinartis.com

(954) 404-8068 ext. 303

Facility Contacts

Richard Preston, MD

Role: primary

Thomas Marbury, MD

Role: primary

Other Identifiers

Qpex-401

Identifier Type: -

Identifier Source: org_study_id