P1, DDI & MAD PK and Safety Study of Xeruborbactam Oral Prodrug in Combo With Ceftibuten in Healthy Participants

NCT ID: NCT06079775

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-30
• Study Completion Date: 2025-01-05

Brief Summary

A Phase 1, Open-Label, Drug-drug Interaction, and Randomized, Double-blind, Controlled, Multiple-dose Pharmacokinetics and Safety Study of Xeruborbactam Oral Prodrug (QPX7831) in Combination with Ceftibuten in Healthy Adult Participants

Detailed Description

Qpex Biopharma, Inc. is developing an oral dosage form that delivers Xeruborbactam, a new boron-based beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases, for oral treatment in combination with a beta-lactam antibiotic.

Ceftibuten is a cephalosporin antibiotic approved in the US for acute exacerbations of chronic bronchitis, acute bacterial otitis media and pharyngitis/tonsillitis.

This Phase 1 study will assess if a PK interaction exists between xeruborbactam oral prodrug and ceftibuten when given in combination at doses of each drug that have previously been shown to be safe. The study will also assess the safety of the combination with dosing over 10 days.

Study Objectives:

1. To assess the safety, tolerability, and PK of single and multiple doses of xeruborbactam oral prodrug and ceftibuten both in combination and alone, in healthy adult participants.

2. To assess whether there is any PK interaction between xeruborbactam oral prodrug and ceftibuten when administered in combination to healthy adult participants.

Conditions

Bacterial Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Single Dose Drug-Drug-Interaction Crossover & Multiple Dose Cohorts

DDI crossover part of the study, subjects will be enrolled into 3 cohorts of 8 subjects each, Cohorts 1, 2, & 3 respectively.

All subjects in Cohorts 1, 2, and 3 will receive a single dose of xeruborbactam oral prodrug (XOP) on Day 1. On Day 6, they will receive a single dose of ceftibuten. On Day 9 they will receive a single combined dose of XOP and ceftibuten.

During the MAD part of the study, subjects will be enrolled into 2 cohorts, Cohorts 4 & 5 respectively.

Subjects in Cohorts 4 (16 subjects) will receive either a combined dose of XOP and ceftibuten, active ceftibuten, or active XOP.

Cohort 4 will be dosed BID on Days 1-9, with last dose on the morning of Day 10.

Subjects in Cohort 5 (15 subjects) will receive active XOP in comb with active ceftibuten which will be admin orally either twice on Day 1 and QD on Days 2-10 (Group 1), BID on Days 1-9 and QD on Day 10 (Group 2), or TID on Days 1-9 and once on Day 10 (Group 3), based on group assignment.

Group Type: EXPERIMENTAL

Xeruborbactam Oral Prodrug

Intervention Type: DRUG

Experimental

Ceftibuten

Intervention Type: DRUG

Experimental

Placebo Comparator to maintain the blind

During Cohort 4, Xeruborbactam Oral Prodrug Placebo and Ceftibuten placebo will be used to maintain the blind. In Cohort 4, ten (10) subjects in each cohort will receive a combined dose of xeruborbactam oral prodrug and ceftibuten. Three (3) subjects in each cohort will receive active ceftibuten capsules with xeruborbactam oral prodrug placebo capsules. Three (3) subjects in each cohort will receive active xeruborbactam oral prodrug capsules with ceftibuten placebo capsules.

Group Type: PLACEBO_COMPARATOR

Xeruborbactam Oral Prodrug Placebo

Intervention Type: DRUG

Placebo Comparator

Ceftibuten Placebo

Intervention Type: DRUG

Placebo Comparator

Interventions

Xeruborbactam Oral Prodrug

Experimental

Intervention Type: DRUG

Ceftibuten

Experimental

Intervention Type: DRUG

Xeruborbactam Oral Prodrug Placebo

Placebo Comparator

Intervention Type: DRUG

Ceftibuten Placebo

Placebo Comparator

Intervention Type: DRUG

Other Intervention Names

QPX7831; QPX7831 Placebo

Eligibility Criteria

Inclusion Criteria

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

Age

1. Participant must be a healthy adult male or female, 18 to 55 years of age (inclusive) at the time of screening.

Type of Participant and Disease Characteristics

2. Participants who are overtly medically healthy with clinically insignificant screening results (eg, laboratory profiles, medical histories, ECGs, physical examination) as assessed by the investigator, sub-investigator, or medical officer.

Weight

3. Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive). Note: BMI = kg/m2 where kg is a weight in kilograms and m2 is a height in meters squared.

Sex and Contraceptive/Barrier Requirements

4. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Male participants:

If male, agree to be sexually abstinent or agree to use 2 approved methods of contraception (refer to inclusion criterion #5) when engaging in sexual activity from study check-in through 30 days following the last administration of the study drug, and to not donate sperm during this same period of time. If the sexual partner is surgically sterile, contraception is not necessary.

5. Female participants:

Females of childbearing potential must either be sexually abstinent for 14 days prior to Day 1 and agree to remain so through 30 days following the last administration of the study drug, OR have been using (or agree to use) 2 of the following acceptable methods of birth control for the times specified:

1. Intra-uterine device (IUD) in place for at least 3 months prior to Day 1 through 30 days following the final dosing of the study drug

2. Barrier method (condom or diaphragm) for at least 14 days prior to Day 1 through 30 days following the final dosing of the study drug

3. Stable hormonal contraceptive for at least 3 months prior to Day 1 and barrier method (condom or diaphragm) for at least 14 days prior to Day 1 through 30 days following final dosing of the study drug

4. Surgical sterilization (vasectomy) of partner at least 6 months prior to Day 1

Informed Consent

6. Capable of giving signed informed consent as described in Appendix 1 Informed Consent Form (Section 10.1.3) that includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

Participants will be excluded from the study if any of the following criteria apply:

Medical Conditions

1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.

2. Documented hypersensitivity reaction or anaphylaxis to any medication, including ceftibuten or other beta-lactam antibiotics (e.g. cephalosporins, penicillins, carbapenems or monobactams) or any excipients used in this formulation.

3. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).

4. Females who are pregnant or lactating.

5. Surgery within the past 3 months prior to Day 1 determined by the investigator, sub-investigator, or medical officer to be clinically relevant.

6. Any acute illness within 30 days prior to Day 1.

7. Any other condition or prior therapy, which, in the opinion of the investigator, sub-investigator, or medical officer would make the participant unsuitable for this study.

Prior/Concomitant Therapy

8. Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to Day 1.

9. Use of any over-the-counter medication, including herbal products, probiotics and vitamins, within the 7 days prior to Day 1. Up to 2 grams per day of paracetamol is allowed for acute events at the discretion of the investigator, sub-investigator, or medical officer.

10. Use of antacids, H2 receptor blockers or proton pump inhibitors 7 days prior to Day 1. This includes calcium carbonate.

Prior/Concurrent Clinical Study Experience

11. Participation in another investigational clinical trial within 30 days prior to Day 1 or within 5 half-lives of the previous investigational drug, whichever is longer.

Diagnostic Assessments

12. QTc corrected according to Fridericia's formula (QTcF) interval > 450 msec for males and > 470 for females or history of prolonged QT syndrome at screening or check-in (Day -1).

13. Calculated creatinine clearance < 80 mL/min (Cockcroft-Gault method) at screening or check-in (Day -1).

14. Any clinically significant abnormalities in laboratory values at screening or check-in (Day -1), in particular:

1. White blood cell count < 3,000/mm3, hemoglobin < 11g/dL

2. Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm3

3. Liver function abnormalities at screening or check-in (Day -1) (defined by an elevation in bilirubin, AST, or ALT > ULN for participants based on age and sex)

15. Blood donation or significant blood loss (ie, > 500 mL) within 56 days prior to Day 1.

16. Plasma donation within 7 days prior to Day 1.

17. Positive urine drug/alcohol testing at screening or check-in (Day -1).

18. History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.

19. Use of more than 5 packs/week of cigarettes (or equivalent amount of nicotine-containing product) within 6 months prior to Day 1. Use of all nicotine containing products 48 hours prior to admission to clinical research unit. Participants must agree to refrain from smoking for the duration of the study.

20. Excessive intake of alcohol, defined as an average daily intake of > 2 standard drinks for women and > 4 standard drinks for men, (standard drink is the equivalent to 4 oz of wine (approximately 12% abv), 12 oz of regular beer (approximately 5% abv), or 1.5 oz of spirits (80 proof).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Qpex Biopharma, Inc.

INDUSTRY

Sponsor Role: lead

Shionogi Inc.

INDUSTRY

Sponsor Role: collaborator

Biomedical Advanced Research and Development Authority

FED

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeff Loutit, MBChB

Role: STUDY_DIRECTOR

Qpex Biopharma, Inc.

Locations

CMAX

Adelaide, South Australia, Australia

Countries

Australia

Other Identifiers

Qpex-102

Identifier Type: -

Identifier Source: org_study_id