Clinical trial NCT02620787: Tedizolid Tissue Penetration in Diabetic Patients With Wound Infections and Healthy Volunteers Via In Vivo Microdialysis
Official title: Comparative Assessment of Tedizolid Tissue Penetration and Pharmacokinetic Profile Between Diabetic Patients With Wound Infections and 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: Merck Sharp & Dohme LLC
First posted: 2015-12-03
Enrollment: 18
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 tedizolid (Sivextro, Merck \& Co.), a novel oxazolidinone antibiotic, 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 6 doses of oral tedizolid 200mg once daily. 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 lactated Ringer's 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:

All Participants:

* Less than 18 years of age
* History of hypersensitivity to tedizolid or linezolid
* History of hypersensitivity to lidocaine or lidocaine derivatives
* Pregnant or breastfeeding
* Presence of anemia, thrombocytopenia, or leukopenia as defined by hematocrit, platelet, or white blood cell count \< 75% of the lower limit of normal
* Concomitant receipt of linezolid
* Any other reason felt by the investigator to potentially affect the outcomes of the study

Experimental Group Only:

* No palpable pedal pulses present
* Participants likely to require multiple surgical interventions during the study period, which therefore could affect placement of the microdialysis catheter

Active Comparator Group Only:

* Positive urine drug screen (cocaine, tetrahydrocannabinol, 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.
* 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. Herbal supplements, hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing intrauterine devices (IUDs), postcoital contraceptive methods), and hormone replacement therapy must be discontinued at least 14 days prior to the first dose of study medication. Depo-Provera® must be discontinued at least 6 months prior to the first dose of study medication.

Primary outcomes:
measure: Tedizolid Tissue Penetration
timeFrame: 48-72 hours
Secondary outcomes:
measure: Tedizolid Area Under the Curve (AUC) in Tissue
timeFrame: 48-72 hours
measure: Tedizolid AUC in Plasma
timeFrame: 48-72 hours
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
Study officials:
affiliation: Hartford Hospital
name: David P Nicolau, PharmD
role: PRINCIPAL_INVESTIGATOR
References: