Clinical trial NCT04144374: Omadacycline Tissue Penetration in Diabetic Patients With Wound Infections and Healthy Volunteers Via In Vivo Microdialysis
Official title: Comparison of Omadacycline Pharmacokinetics and Soft-Tissue Penetration in Diabetic Patients With Wound Infections Versus Healthy Volunteers Via In Vivo Microdialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Wound Infection
Healthy Volunteers
Lead sponsor: Hartford Hospital
Sponsor class: OTHER
Collaborators: name: Paratek Pharmaceuticals Inc
First posted: 2019-10-30
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Omadacycline Tissue Penetration.
timeFrame: 48-72 hours
Secondary outcomes:
measure: Omadacycline Area Under the Curve (AUC) in Tissue
timeFrame: 48-72 hours
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
Study officials:
affiliation: Center for Anti-Infective Research and Development, Hartford Hospital
name: David P Nicolau, PharmD
role: PRINCIPAL_INVESTIGATOR
References: