PK & Safety Study of Xeruborbactam Oral Prodrug Combined With Ceftibuten in Participants With Renal Impairment

NCT06157242 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: Qpex-103
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase 1, open-label, single-dose study to determine the safety and pharmacokinetics of ORAvance (ceftibuten/xeruborbactam oral prodrug \[QPX7831\]) in participants with renal impairment

Conditions

Bacterial Infections

Keywords

beta-lactamase inhibitor

Outcome Measures

Primary Outcomes (7)

• Incidence of Treatment Emergent adverse events by subject and by group

  Number of patients with Treatment-Emergent Adverse Events by subject, by group, severity and relationship to treatment

  10 days

• Number of patients with changes from baseline in safety parameters

  Number of patients with changes in safety parameters before and after dosing by subject and group

  10 days

• Peak plasma Concentration measurements by subject and by group (Cmax)

  Comparison will be performed between the groups for concentration measurements (Cmax). Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed.

  10 days

• Time concentration data measurements by subject and by group (Tmax)

  Comparison will be performed between the groups for time concentration data measurements (Tmax)

  10 days

• Area under the plasma concentration versus time curve (AUC) between groups

  Comparison will be performed between the groups for area under the plasma concentration versus time curve (AUC) Mean graphical presentation of the data will be reported. Statistical analysis of exposure parameters will be performed.

  10 days

• Urine Pharmacokinetic (PK) amount excreted by subject and by group

  Urine Pharmacokinetic (PK) parameters such as amount excreted will be calculated from urinary excretion data

  10 days

• Urine Pharmacokinetic (PK) % dose excreted by subject and by group

  Urine Pharmacokinetic (PK) parameters such as amount of % dose excreted will be calculated from urinary excretion data

  10 days

Study Arms (1)

Open Label, Single Dose Combination of Ceftibuten & Xeruborbactam oral prodrug

EXPERIMENTAL

24 pts will be enrolled with varying degrees of RI as well as 8 participants with normal renal function (NRF). 8 participants will be enrolled in each group (G) based on estimated glomerular function rate (eGFR) at screening: * G1: Mild RI (eGFR 60 to 90 mL/min/1.73m2 calculated using the 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/1.73m2 calculated using the CKD-EPI equation adjusted for the participant's BSA) * G3: Severe RI (eGFR \< 30 mL/min/1.73m2 calculated using the CKD-EPI equation) not receiving dialysis therapy * G4: Healthy participants with NRF matched to patients in Groups 1, 2 and 3 based on age, gender and BMI All pts will receive a single dose of ceftibuten \& QPX7831 on Day 1. Pts will remain in the clinic until completion of the post-dose procedures on Day 8. Participants will be contacted by phone between Days 10-12 for follow-up.

Drug: Xeruborbactam Oral Prodrug; Drug: Ceftibuten

Interventions

Xeruborbactam Oral Prodrug DRUG

Experimental

Also known as: QPX7831

Open Label, Single Dose Combination of Ceftibuten & Xeruborbactam oral prodrug

Ceftibuten DRUG

Experimental

Open Label, Single Dose Combination of Ceftibuten & Xeruborbactam oral prodrug

Eligibility Criteria

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

You may qualify if:

• 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.
• Males and females at least 18 years of age, at the time of consent.
• Females of childbearing potential must either be sexually abstinent for 14 days prior to day 1 and remain so through 30 days following the last administration of the study intervention, OR have been using (or agree to use) 2 acceptable methods of birth control for the times specified:
• Intra-uterine device in place for at least 3 months prior to day 1 through 30 days following the final dosing of the study intervention
• Barrier method (condom or diaphragm) for at least 14 days prior to day 1 through 30 days following the final dosing of the study intervention
• Stable hormonal contraceptive for at least 3 months prior to day 1 through 30 days following final dosing of the study intervention
• Surgical sterilization (vasectomy) of partner at least 6 months prior to day 1
• Females of non-childbearing potential must either be postmenopausal (defined as 12 months spontaneous amenorrhea) with a serum follicle stimulating hormone (FSH) level in the laboratory defined postmenopausal range or have undergone 1 of the following sterilization procedures detailed in the study protocol at least 6 months prior to day 1:
• Bilateral tubal ligation
• Hysterectomy
• Hysterectomy with unilateral or bilateral oophorectomy
• Bilateral oophorectomy
• Have a BMI ≥ 18.5 kg/m2 and ≤ 45 kg/m2, inclusive.
• Have sufficient peripheral vascular access, based on the site's assessment, for PK blood sample collection.

You may not qualify if:

• All Participants:
• Have unstable or new medical conditions (eg, cardiovascular, respiratory, hepatic, renal, gastrointestinal, autoimmune, endocrine, or neurological disorders) which have occurred in the 3 months prior to the first dose of study intervention and which are capable of altering the absorption, distribution, metabolism, or elimination of drugs or, in the opinion of the investigator, constitute a risk factor to participating in the study and/or receiving study intervention.
• Documented hypersensitivity reaction or anaphylaxis to any antibiotic including ceftibuten or other beta-lactam antibiotics (eg, cephalosporins, penicillins, carbapenems, or monobactams) or any excipients used in this formulation.
• History of clinically significant seizures, head injury, or meningitis.
• Current evidence or history of malignancy, except squamous cell carcinoma or basal cell carcinoma of the skin, in the 2 years prior to day -1 with no evidence of recurrence.
• Females who are pregnant, lactating, or have a positive pregnancy test at the screening visit or day -1.
• Previously received any dose of ORAvance (ceftibuten/xeruborbactam oral prodrug), xeruborbactam oral prodrug, xeruborbactam or prodrug alone.
• Received any investigational drug within 30 days or 5 half-lives, whichever is longer, prior to day 1 of the current 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 48 hours prior to day -1 until the day of discharge from the study.
• Positive drug test at the screening visit or day -1 unless results can be explained by a prescription medication and/or recent history (ie, within 6 months prior to day -1) of abuse of prescription or illicit drugs as detailed in the study protocol.
• Positive alcohol test at the screening visit or day -1 and/or recent history (ie, within 6 months prior to day -1) of excessive alcohol intake as defined in the study protocol.
• Excessive intake of alcohol, defined as an average weekly intake of \> 14 standard drinks, (standard drink is the equivalent to 120 ml of wine (approximately 12% abv), 350 ml of regular beer (approximately 5% abv), or 45 ml of spirits (40% abv).

Sponsors & Collaborators

• Qpex Biopharma, Inc.: lead
• Shionogi Inc.: collaborator
• Biomedical Advanced Research and Development Authority: collaborator

Study Sites (2)

University of Miami Clinical Pharmacology

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Bacterial Infections

Interventions

Ceftibuten

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jeff Loutit, MBChB

  Qpex Biopharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, single dose design

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 5, 2023
• Study Start: November 10, 2024
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)