Bacterial Infections
Conditions
Keywords
beta-lactamase inhibitor
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.
Interventions
DRUGCefiderocol/Xeruborbactam
A fixed dose combination of intravenous cefiderocol and intravenous xeruborbactam
Sponsors
Shionogi Inc.
Biomedical Advanced Research and Development Authority
Qpex Biopharma, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, single-dose
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) by participant and by group | 11-22 days (+/- 2) | Number of participants with treatment-emergent adverse events by severity and relationship to treatment |
| Number of participants with changes from baseline in safety parameters | 11-22 days (+/- 2) | Number of participants with changes in safety parameters before and after dosing by subject and group |
| Maximum plasma concentration measurements by subject and by group (Cmax) | 11-22 days (+/- 2) | Comparison will be performed between the groups for maximum plasma concentration (Cmax). |
| Time to maximum plasma concentration (Tmax) | 11-22 days (+/- 2) | Comparison will be performed between the groups for time to maximum plasma concentration (Tmax) |
| Area under the plasma concentration versus time curve (AUC) | 11-22 days (+/- 2) | Comparison will be performed between the groups for area under the plasma concentration versus time curve (AUC) |
| Cumulative amount of drug excreted as unchanged in the urine (Aeu) | 11-22 days (+/- 2) | This parameter will not be estimated in Group 5 |
| Cumulative amount of drug excreted as unchanged in the dialysate (Aed) | 11-22 days (+/- 2) | This parameter will be estimated only in Group 5. Urine pharmacokinetic (PK) parameters will be calculated from urinary excretion and dialysate data. |
Countries
United States
Contacts
Primary ContactGrigor Mamikonyan, PharmD,PhD
Outcome results
None listed