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

Primary Purpose

Diabetes, Wound Infection, Healthy Volunteers

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tedizolid

Microdialysis Catheter Insertion

About this trial

This is an interventional other trial for Diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Hartford Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Diabetic Wound Infection

Healthy Volunteers

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Tedizolid Tissue Penetration

The ratio of tedizolid tissue concentrations to blood concentrations following the final tedizolid dose

Secondary Outcome Measures

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.

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

Full Information

NCT ID

NCT02620787

First Posted

December 1, 2015

Last Updated

July 31, 2018

Sponsor

Hartford Hospital

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02620787

Brief Title

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

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

February 23, 2016 (Actual)

Primary Completion Date

March 1, 2017 (Actual)

Study Completion Date

March 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hartford Hospital

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes, Wound Infection, Healthy Volunteers

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Diabetic Wound Infection

Arm Type

Experimental

Arm Description

Arm Title

Healthy Volunteers

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tedizolid

Other Intervention Name(s)

Sivextro

Intervention Type

Procedure

Intervention Name(s)

Microdialysis Catheter Insertion

Intervention Description

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.

Primary Outcome Measure Information:

Title

Tedizolid Tissue Penetration

Description

The ratio of tedizolid tissue concentrations to blood concentrations following the final tedizolid dose

Time Frame

48-72 hours

Secondary Outcome Measure Information:

Title

Tedizolid Area Under the Curve (AUC) in Tissue

Description

Time Frame

48-72 hours

Title

Tedizolid AUC in Plasma

Description

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

Time Frame

48-72 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David P Nicolau, PharmD

Organizational Affiliation

Hartford Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hartford Hospital

City

Hartford

State/Province

Connecticut

ZIP/Postal Code

06102

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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