IV cefiderocol plus xeruborbactam for people with reduced kidney function

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

This study will test a single IV dose of cefiderocol combined with xeruborbactam in adults with varying kidney impairment to see how the drugs are processed and whether they are safe.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Qpex Biopharma, Inc. (Industry-sponsored)
• Locations: 2 sites (Miami, Florida and 1 other locations)
• Trial ID: NCT07104162 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, open-label, single-dose study comparing pharmacokinetics and safety of intravenous cefiderocol/xeruborbactam across participants with normal renal function, mild, moderate, and severe stable renal impairment, and end-stage renal disease (ESRD) receiving intermittent hemodialysis. Participants will receive a single IV dose and undergo serial blood sampling and safety monitoring to characterize drug exposure, clearance, and tolerability. The study will compare PK parameters between renal function groups and evaluate the effect of hemodialysis on drug removal. Findings will be used to inform dosing recommendations for patients with impaired renal function.

Who should consider this trial

Good fit: Adults aged 18–80 with stable mild to severe renal impairment or ESRD on intermittent hemodialysis, and healthy controls with normal kidney function, who can give informed consent are the intended participants.

Not a fit: People under 18 or over 80, pregnant or breastfeeding individuals, patients with unstable or rapidly changing kidney function, or those with active severe infections are unlikely to benefit from this single-dose PK study.

Why it matters

Potential benefit: If successful, the results could provide dosing guidance that helps make this antibiotic combination safer and more effective for patients with impaired kidneys.

How similar studies have performed: Cefiderocol alone is approved for certain serious infections and prior PK studies in renal impairment have informed dosing, but combining it with the investigational beta‑lactamase inhibitor xeruborbactam is a newer approach that remains to be proven.

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:

An individual must not meet any of the following exclusion criteria to be eligible to participate in the study:

* 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)

Where this trial is running

Miami, Florida and 1 other locations

• University of Miami Clinical Pharmacology — Miami, Florida, United States (Recruiting)
• Orlando Clinical Research Center — Orlando, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Thomas Marbury, MD — Orlando Clinical Research Center
• Study coordinator: Grigor Mamikonyan, PharmD,PhD

Conditions Bacterial Infections; beta-lactamase inhibitor