Testing a new oral treatment for bacterial infections in healthy adults

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

This study is testing a new oral treatment for bacterial infections to see if it works safely when combined with another antibiotic in healthy adults.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 71 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Qpex Biopharma, Inc. (Industry-sponsored)
• Locations: 1 site (Adelaide, South Australia)
• Trial ID: NCT06079775 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial evaluates the safety and pharmacokinetics of an oral prodrug called Xeruborbactam in combination with the antibiotic Ceftibuten in healthy adult participants. The study aims to determine if there is any drug-drug interaction between these two medications when administered together over a period of 10 days. Participants will receive either the active drugs or placebos in a randomized, double-blind manner to ensure unbiased results. The trial will include assessments of tolerability and safety through clinical evaluations and laboratory tests.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy adults aged 18 to 55 with a BMI between 18.5 and 29.9.

Not a fit: Patients with existing medical conditions or those outside the specified age and weight criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a new effective oral treatment option for bacterial infections.

How similar studies have performed: While this approach is novel, similar studies involving beta-lactamase inhibitors have shown promise in treating bacterial infections.

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)

    Other Exclusion Criteria
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).

Where this trial is running

Adelaide, South Australia

• Cmax — Adelaide, South Australia, Australia (Recruiting)

Study contacts

• Study coordinator: Shawnee Gehrke, MPH

Conditions Bacterial Infections; beta-lactamase inhibitor