Tedizolid Tissue Penetration in Diabetic Patients With Wound Infections and Healthy Volunteers Via In Vivo Microdialysis

Comparative Assessment of Tedizolid Tissue Penetration and Pharmacokinetic Profile Between Diabetic Patients With Wound Infections and Healthy Volunteers Via In Vivo Microdialysis

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.

Study Overview

• Status: Completed
• Conditions: Diabetes; Healthy Volunteers; Wound Infection
• Intervention / Treatment: Procedure: Microdialysis Catheter Insertion; Drug: Tedizolid

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diabetic Wound Infection; Participants with a documented medical history of Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound infection of the lower limb will receive 3 to 6 doses of oral tedizolid 200mg once daily, followed by sampling of interstitial tissue fluid at the margin of the wound by a microdialysis probe over 24 hours following the last dose (e.g., 48-72 hours).	Procedure: Microdialysis Catheter Insertion; A 20 kila-Dalton 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.; Drug: Tedizolid; Other Names: Sivextro
Active Comparator: Healthy Volunteers; Participants will be male or female healthy adult volunteers with no significant medical or medication history. Participants will receive 3 to 6 doses of oral tedizolid 200mg once daily, followed by sampling of interstitial tissue fluid at the margin of the wound by a microdialysis probe over 24 hours following the last dose (e.g., 48-72 hours).	Procedure: Microdialysis Catheter Insertion; A 20 kila-Dalton 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.; Drug: Tedizolid; Other Names: Sivextro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tedizolid Tissue Penetration	The ratio of tedizolid tissue concentrations to blood concentrations following the final tedizolid dose	48-72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tedizolid Area Under the Curve (AUC) in Tissue	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 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.	48-72 hours
Tedizolid AUC in Plasma	The area under the plasma drug concentration-time curve (AUC) reflects the actual plasma exposure to drug after administration of a dose of the drug and is expressed in mg*h/L	48-72 hours

Collaborators and Investigators

• Sponsor: Hartford Hospital
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: David P Nicolau, PharmD, Hartford Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2016
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: December 1, 2015
• First Submitted That Met QC Criteria: December 1, 2015
• First Posted (Estimate): December 3, 2015

Study Record Updates

• Last Update Posted (Actual): January 15, 2019
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Wounds and Injuries; Wound Infection; Anti-Infective Agents; Anti-Bacterial Agents; Tedizolid
• Other Study ID Numbers: Nicolau-53466

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No