Tebipenem (SPR994) Tissue Penetration in Diabetic Patients With Wound Infections and Healthy Volunteers Via In Vivo Microdialysis

Phase 1

Completed

• Conditions: Diabetes; Wound Infection; Healthy Volunteers; ABSSSI
• Interventions: Drug: Tebipenem Pivoxil Hydrobromide

• Registration Number: NCT04919954
• Lead Sponsor: Hartford Hospital

Brief Summary

This study will determine the tissue penetration of a broad-spectrum orally bioavailable carbapenem, tebipenem pivoxil hydrobromide (SPR994) (Spero Therapeutics, Inc.), into the extracellular, interstitial fluid of soft tissue in diabetic patients with lower limb wound infections. Penetration will be compared with a group of healthy volunteer control participants.

Detailed Description

This study will enroll 10 patients with diabetes who are admitted with a lower limb wound infection and 6 healthy volunteer control participants. The study will take place in an inpatient unit at Hartford Hospital for all patients and in the Clinical Research Center at Hartford Hospital for all healthy volunteers. All participants will receive 3 to 7 doses of tebipenem pivoxil hydrobromide (300 mg or 600 mg orally every 8 hours depending on renal function). A microdialysis probe (Mdialysis Inc., N. Chelmsford, MA) will be inserted into the subcutaneous soft tissue near the margin of the wound (patients) or in the thigh (healthy volunteers). The microdialysis probe is perfused with normal saline solution and samples are collected for the 8 hours following the final dose. A peripheral intravenous catheter will be inserted into an arm vein to collect blood samples simultaneously with microdialysis samples. Concentrations in tissue are compared with blood to determine percent penetration.

Study Timeline

• Study First Submitted: 2021-06-03
• Study First Submitted QC: 2021-06-03
• Study First Posted: 2021-06-09
• Study Start: 2021-07-01
• Primary Completion: 2022-08-30
• Study Completion: 2022-12-23
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-18
• Last Update Posted: 2023-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Diabetic Wound Infection	Tebipenem Pivoxil Hydrobromide	Participants with a documented medical history of Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound infection of the lower limb will receive 3 to 7 doses of tebipenem, followed by sampling of interstitial tissue fluid at the margin of the wound by a microdialysis probe over 8 hours following the last dose.
Healthy Volunteers	Tebipenem Pivoxil Hydrobromide	Participants will be male or female healthy adult volunteers with no significant medical or medication history. Participants will receive 3 doses of tebipenem, followed by sampling of interstitial tissue fluid by a microdialysis probe inserted in a thigh over 8 hours following the last dose.

Primary Outcome Measures

Name	Time	Method
Tebipenem Pivoxil Hydrobromide Tissue Penetration	8 hours	The ratio of tebipenem tissue concentrations to blood concentrations following the final tebipenem dose

Secondary Outcome Measures

Name	Time	Method
Tebipenem Pivoxil Hydrobromide Area Under the Curve (AUC) in Tissue	8 hours	The area under the drug concentration-time curve (AUC) in tissue reflects the actual tissue exposure to drug after administration of a dose of the drug and is expressed in mg\*h/L. Venous blood will be obtained via peripheral intravenous catheter immediately before administration of the last dose (pre-dose timepoint), and at 9 time-points post-dose. Dialysate samples of 120μL will be collected in 200µL microvials simultaneously with plasma samples.

Trial Locations

Locations (1)

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States