Safety, Tolerability, and Pharmacokinetics of Sulopenem in Adolescents

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

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous sulopenem and oral sulopenem etzadroxil/probenecid in adolescent patients.

Study Overview

• Status: Withdrawn
• Conditions: Intraabdominal Infections; Urinary Tract Infections; Pyelonephritis Acute
• Intervention / Treatment: Drug: Sulopenem

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will be screened for eligibility. Hospitalized patients who are 12-18 years of age and who are receiving background antibiotic treatment for uncomplicated urinary tract infection, complicated urinary tract infection, acute pyelonephritis, or complicated intraabdominal infection, and who meet eligibility requirements will receive a single 1000 mg IV dose of sulopenem on Day 1. The following day, patients will receive a single dose of 500 mg of sulopenem etzadroxil and 500 mg of probenecid given orally as a bilayer tablet. During treatment, pharmacokinetic samples will be collected and patients will be monitored for safety and tolerability.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Medical facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.
2. Patient is male or female adolescent who are ≥12 and <18 years of age.
3. Patient has a diagnosis of uUTI, cUTI, AP, or cIAI as documented by the treating physician
4. Patient will be hospitalized for urinary tract infection, acute pyelonephritis, or complicated intraabdominal infection for at least 48 hours and be receiving appropriate anti-infective treatment.
5. Patient must have sufficient venous access to permit administration of study drug, collection of PK samples, and monitoring of laboratory safety variables.
6. Female patients who are post-menarche must not be pregnant or breast feeding and must have a documented negative serum pregnancy test at Screening.
7. Post-menarchal 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.
8. Patient must be willing to follow all study procedures.

Exclusion Criteria:

1. Patient has creatinine clearance <90 mL/min using the Cockcroft-Gault formula.
2. Patient is unable to tolerate oral medications.
3. Patient has presence of Endocarditis, Meningitis, Necrotizing fasciitis, or Gas gangrene
4. Patient has signs of severe sepsis
5. Patient has evidence of active liver disease or hepatic dysfunction
6. Patient has neutropenia with 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 cephalosporins, known allergy to probenecid, or severe allergic reactions to any drug in the past.
10. Patient has history of intolerance to β-lactam antibiotics, including but not limited to a history of clinically significant diarrhea/loose stools.
11. Patient has a history of hypersensitivity to the study drug or any of the excipients or to medicinal products with similar chemical structures.
12. Patient has involvement in the planning and/or conduct of this study
13. 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.
14. Patient has definite or suspected personal history or family history of clinically significant adverse drug reactions.
15. 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.
16. Patient had treatment in the previous 3 months with any drug known to have a well-defined potential for hepatotoxicity (eg, halothane).
17. Patient weighs <35 kg.
18. Patient is pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sulopenem; Sulopenem intravenous 1000 mg (single dose) on Day 1 followed by oral sulopenem etzadroxil/probenecid 500 mg/500 mg (single dose) on Day 2.	Drug: Sulopenem; sulopenem intravenous 1000 mg on Day 1 and then sulopenem etzadroxil/probenecid oral 500 mg/500 mg on Day 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration	Maximum plasma concentration (Cmax) of sulopenem at multiple timepoints after dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum plasma concentration	Time to maximum plasma concentration (Tmax) of sulopenem at multiple timepoints after dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Time above minimum inhibitory concentration	Time above minimum inhibitory concentration (MIC) at multiple timepoints after dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Area under the plasma concentration-time curve from time zero to time of last quantifiable plasma concentration	Area under the plasma concentration-time curve (AUC) from time zero to time of last quantifiable plasma concentration at multiple timepoints after dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Area under the plasma concentration-time curve from time zero extrapolated to infinity	Area under the plasma concentration-time curve (AUC) from time zero extrapolated to infinity at multiple timepoints after dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Percentage of area under the concentration-time curve extrapolated	Percentage of area under the concentration-time curve (AUC) extrapolated at multiple timepoints after dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Terminal elimination half-life	Terminal elimination half-life at multiple timepoints after dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Total body clearance for intravenous administration	Total body clearance for intravenous administration at multiple timepoints after intravenous dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Apparent total body clearance for oral administration	Apparent total body clearance for oral administration at multiple timepoints after oral dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Volume of distribution for intravenous administration	Volume of distribution for intravenous administration at multiple timepoints after intravenous dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose
Apparent volume of distribution for oral administration	Apparent volume of distribution for oral administration at multiple timepoints after oral dose	To be measured at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 9.0, 10.0, and 12.0 hours post dose

Collaborators and Investigators

• Sponsor: Iterum Therapeutics, International Limited
• Investigators: Study Director: Steven I Aronin, MD, Employee

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Actual): March 25, 2022
• Study Completion (Actual): April 4, 2022

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): June 13, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Nephritis; Nephritis, Interstitial; Pyelitis; Infections; Communicable Diseases; Intraabdominal Infections; Urinary Tract Infections; Pyelonephritis
• Other Study ID Numbers: IT001-106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No