Diabetes, Wound Infection, Healthy Volunteers
Conditions
Brief summary
This study will determine the tissue penetration of the novel tetracycline antibiotic, omadacycline (Nuzyra, Paratek Pharmaceuticals, 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 5 doses of omadacycline (200mg IV once daily on day 1, transitioned to 300 mg by mouth thereafter). 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 24 hours following the final dose (i.e., 48-72 hours). 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
DRUGOmadacycline
Omadacycline will be administered 200 mg IV once daily on day 1 followed by omadacycline 300 mg by mouth once daily for 2-4 doses.
PROCEDUREMicrodialysis Catheter Insertion
A 20 kilodalton microdialysis probe (63 MD catheter; MDialysis Inc., N. Chelmsford, MA) will be inserted into the subcutaneous tissue at the margin of the wound (patient group) or in the thigh tissue (healthy volunteers). The probe will be left in place for the final dose and all tissue sampling procedures thereafter. This probe is perfused with a physiologic solution to collect interstitial fluid samples. The probe will then be removed after completion of sample collection.
Sponsors
Paratek Pharmaceuticals Inc
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
Inclusion criteria
Experimental: Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound infection of the lower limb Active Comparator: Healthy Adult Volunteer
Exclusion criteria
Participants in the study or control group will be excluded if any of the following criteria are met: * Less than 18 years of age * History of hypersensitivity to omadacycline or any tetracycline based molecule * History of hypersensitivity to lidocaine or lidocaine derivatives * Pregnant or breastfeeding * Concomitant receipt of any tetracycline based antibiotic therapy * Any other documented reason felt by the investigator to potentially affect the outcomes of the study Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Omadacycline Tissue Penetration. | 48-72 hours | The ratio of omadacycline tissue concentrations to blood concentrations following the final omadacycline dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Omadacycline Area Under the Curve (AUC) in Tissue | 48-72 hours | he 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 was obtained via peripheral intravenous catheter at 48 hours from the start of the first dose (i.e., immediately before administration of the 3rd dose), and at 49, 50, 50.5, 51, 51.5, 52, 54, 56, 60, 64 and 72 hours. Dialysate samples of 120μL were collected in 200µL microvials simultaneously with plasma at 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 64, 68 and 72 hours following administration of the first dose. |
Countries
United States
Outcome results
None listed