How adolescents absorb and clear sulopenem etzadroxil with probenecid

A Phase 1, Multi-Center, Open-Label Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Sulopenem Etzadroxil + Probenecid in Adolescent Patients With Bacterial Infection

This will test a single oral dose of sulopenem etzadroxil plus probenecid in adolescents 12–17 with bacterial infections to see how their bodies process the drug and whether it is safe and tolerable.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 12 Years to 17 Years
• Sex: All
• Sponsor: Iterum Therapeutics, International Limited (Industry-sponsored)
• Locations: 1 site (Little Rock, Arkansas)
• Trial ID: NCT07092813 on ClinicalTrials.gov

What this trial studies

This is an open-label Phase 1 study enrolling adolescent inpatients and outpatients diagnosed with bacterial infections who are receiving standard-of-care antibiotics. Participants will take a single oral dose of sulopenem etzadroxil plus probenecid and provide timed blood and urine samples to characterize pharmacokinetics. The primary aim is to measure how the drug is absorbed, distributed, metabolized, and excreted in adolescents, with safety and tolerability monitored as secondary outcomes. The study is multicenter and will include standard safety labs and adverse event monitoring during the sampling period.

Who should consider this trial

Good fit: Ideal candidates are adolescents aged 12 to 17 with a physician-diagnosed bacterial infection who are receiving appropriate antibiotics, can provide required blood and urine samples, and whose parent or guardian can give informed consent.

Not a fit: Patients unlikely to benefit include those younger than 12 or 18 and older, those with infections resistant to carbapenems, pregnant or breastfeeding adolescents, or anyone unable to provide venous access or required samples.

Why it matters

Potential benefit: If successful, the results could support appropriate dosing and safety information for using oral sulopenem etzadroxil plus probenecid in adolescents, expanding treatment options.

How similar studies have performed: Oral sulopenem etzadroxil plus probenecid has been approved for uncomplicated UTI in adults, but pediatric pharmacokinetic data are lacking, so this Phase 1 study extends known adult information to adolescents.

Eligibility criteria

Inclusion Criteria:

1. Patient's parent/both parents or guardian must provide written informed consent and a statement of assent from the adolescent patient (if required by Institutional Review Board \[IRB\] according to local regulations and guidelines) must be obtained prior to any study-related procedures. Communication should take place between the Investigator, parent(s)/guardian, and adolescent patient to confirm understanding and compliance with the study requirements.
2. Patient is male or female adolescent who are more than or equal to 12 and \<18 years of age.
3. Patient has a diagnosis of a bacterial infection as documented by the treating physician
4. Patient will be receiving appropriate anti-infective treatment for a bacterial infection.
5. Patient must have sufficient venous access to permit collection of PK samples and monitoring of laboratory safety variables.
6. Female patients who are postmenarchal must not be pregnant, or breast feeding and must have a documented negative pregnancy test at Screening.
7. Postmenarchal females and post-pubertal males must agree to use a highly effective method of birth control with partners of childbearing potential throughout the duration of the study and for 1 month following the last dose of study drug.

   NOTE: A highly effective method of birth control is defined as one that results in a low failure rate (i.e., \<1% per year) when used consistently and correctly. This includes sexual abstinence, implants, some intrauterine devices, or a vasectomized partner. A vasectomy or a condom used with a spermicide is a medically acceptable form of birth control for males.
8. Patient must be willing to follow all study procedures.

Exclusion Criteria:

1. Known renal insufficiency.
2. Patient is unable to tolerate oral medications.
3. Patient has presence of any of the following conditions:

   1. Endocarditis
   2. Meningitis
   3. Necrotizing fasciitis
   4. Gas gangrene
4. Patient has signs of severe sepsis including:

   1. Shock or profound hypotension that is not responsive to fluid challenge.
   2. Disseminated intravascular coagulation as evidenced by prothrombin time or partial thromboplastin time more than or equal to 2 × the upper limit of normal (ULN) or platelets \<50% of the lower limit of the normal.
5. Patient has known active liver disease or hepatic dysfunction (except a confirmed diagnosis of Gilbert's disease) defined as non-transient elevations of aspartate aminotransferase or alanine aminotransferase level elevations more than or equal to 3 × the ULN or non-transient total bilirubin more than or equal to 2 × the ULN.
6. Known neutropenia (absolute neutrophil count \<500 cells/mm3).
7. Patient has history of solid organ transplantation reported at any time.
8. Patient has any finding that, in the view of the Investigator, would compromise the patient's safety requirements.
9. Patient has known allergies to penicillin, carbapenems, and/or cephalosporin antibiotics, known allergy to probenecid, or severe allergic reactions to any drug in the past.
10. Patient has a history of hypersensitivity to the study drug or any of the excipients or to medicinal products with similar chemical structures.
11. Patient or parent/legal guardian has involvement in the planning and/or conduct of this study (applies to both Iterum Therapeutics staff and/or staff at the study sites).
12. Patient has participated in any other clinical study where an investigational product was ingested within 30 days or 5 half-lives of the drug (whichever is longer) prior to the current study.
13. Patient has definite or suspected personal history or family history of clinically significant adverse drug reactions.
14. Patient has history or presence of GI, hepatic, or renal disease, or other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.
15. Patient had treatment in the previous 3 months with any drug known to have a well-defined potential for hepatotoxicity (e.g., halothane).
16. Patient weighs \<30 kg.
17. Patient is pregnant or lactating.
18. Patient has received a carbapenem as their standard of care therapy to treat the diagnosed bacterial infection.

Where this trial is running

Little Rock, Arkansas

• Medical facility — Little Rock, Arkansas, United States (Recruiting)

Study contacts

• Study coordinator: Senior Vice President and Head of Clinical Development

Conditions Pharmacokinetics After Oral Intake; Pharmacokinetics; Adolescents; Sulopenem etzadroxil; Probenecid; Sulopenem; Phase 1