ABSSSI, Diabetes, Healthy Volunteers, Wound Infection
Conditions
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.
Interventions
DRUGTebipenem Pivoxil Hydrobromide
Tebipenem 300 mg or 600 mg will be administered orally every 8 hours for total of 3 to 7 doses
Sponsors
Spero Therapeutics
Hartford Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Exclusion criteria
- All patients/participants Participants in the diabetic wound group or healthy volunteer group will be excluded if any of the following criteria are met: 1. Less than 18 years of age 2. History of hypersensitivity or allergy to tebipenem or its derivatives and any β-lactam antibiotic 3. History of hypersensitivity to lidocaine or lidocaine derivatives 4. Concurrently receiving probenecid. 5. Males who are not surgically sterilized (with female partners of childbearing potential) and females of childbearing potential must agree to use two highly effective methods of contraception from screening, during this trial, and for 90 days after the last dose of study drug. A woman is considered of childbearing potential unless postmenopausal (≥1 year without menses) or surgically sterilized via bilateral oophorectomy, hysterectomy, bilateral tubal ligation, or successful Essure® placement with a documented confirmation test at least 90 days after the procedure. Highly effective contraception is defined as a method of contraception that has a less than 1% failure rate when used consistently and correctly. These methods are as follows: * Hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants). * Intrauterine device or intrauterine system. * Double-barrier methods of contraception (eg, male condom with diaphragm or male condom with cervical cap). * Monogamous relationship with a vasectomized partner. * Total abstinence, in accordance with the lifestyle of the subject. 6. Any other documented reason felt by the investigator to potentially affect the outcomes of the study Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tebipenem Pivoxil Hydrobromide Tissue Penetration | 8 hours | The ratio of tebipenem tissue concentrations to blood concentrations following the final tebipenem dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed