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Omadacycline 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

Omadacycline

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:

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.

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 5 doses of omadacycline 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 doses of omadacycline 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

Omadacycline Tissue Penetration.

The ratio of omadacycline tissue concentrations to blood concentrations following the final omadacycline dose.

Secondary Outcome Measures

Omadacycline Area Under the Curve (AUC) in Tissue

he 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.

Full Information

NCT ID

NCT04144374

First Posted

October 28, 2019

Last Updated

August 23, 2021

Sponsor

Hartford Hospital

Collaborators

Paratek Pharmaceuticals Inc

1. Study Identification

Unique Protocol Identification Number

NCT04144374

Brief Title

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

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

February 10, 2020 (Actual)

Primary Completion Date

July 12, 2021 (Actual)

Study Completion Date

July 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hartford Hospital

Collaborators

Paratek Pharmaceuticals Inc

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 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.

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

14 (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)

Omadacycline

Other Intervention Name(s)

Nuzyra

Intervention Description

Omadacycline will be administered 200 mg IV once daily on day 1 followed by omadacycline 300 mg by mouth once daily for 2-4 doses.

Intervention Type

Procedure

Intervention Name(s)

Microdialysis Catheter Insertion

Intervention Description

A 20 kilodalton 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

Omadacycline Tissue Penetration.

Description

The ratio of omadacycline tissue concentrations to blood concentrations following the final omadacycline dose.

Time Frame

48-72 hours

Secondary Outcome Measure Information:

Title

Omadacycline Area Under the Curve (AUC) in Tissue

Description

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: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David P Nicolau, PharmD

Organizational Affiliation

Center for Anti-Infective Research and Development, 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

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

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