Omadacycline Tissue Penetration in Diabetic Patients With Wound Infections and Healthy Volunteers Via In Vivo Microdialysis
Omadacycline Tissue Penetration in Diabetic Patients With Wound Infections and Healthy Volunteers Via In Vivo Microdialysis
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.
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.
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 Exclusion Criteria for Diabetic Patient Study Group:

 -  Participants likely to require multiple surgical interventions during the study
 period, which therefore could affect placement of the microdialysis catheter

 Additional Criteria for Healthy Volunteer Control Group:

 -  Body Mass Index (BMI) ≥ 35 kg/m2

 -  Serum creatinine greater than 1.5 mg/dl or creatinine clearance (CrCl) < 50ml/min, as
 calculated by Cockroft-Gault using ideal body weight for all participants

 -  Presence of anemia, thrombocytopenia, or leukopenia as defined by hematocrit,
 platelet, or white blood cell count < 75% of the lower limit of normal

 -  Aspartate transaminase, alanine aminotransferase, or alkaline phosphatase greater than
 five times upper limit of normal

 -  Total bilirubin greater than three times the upper limit of normal

 -  Any known active co-morbidity listed on medical history or that becomes apparent
 during physical examination

 -  Positive urine drug screen (cocaine, THC, opiates, benzodiazepines, and amphetamines)

 -  History of regular alcohol consumption exceeding 7 drinks/week for females or 14
 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of
 hard liquor) within 6 months of screening.

 -  Use of tobacco- or nicotine-containing products in excess of the equivalence of 5
 cigarettes per day.

 -  Consumption of caffeine between Study Days 1 and 4

 -  Use of prescription or nonprescription drugs, vitamins, or dietary supplements within
 7 days or 5 half-lives (whichever is longer) prior to the first dose of study
 medication, with the exception of acetaminophen at doses of ≤ 1 g/day. The use of
 hormonal methods of contraception (including oral and transdermal contraceptives,
 injectable progesterone, progestin subdermal implants, progesterone-releasing IUDs,
 postcoital contraceptive methods) are permitted.