Trial Outcomes & Findings for Tedizolid Tissue Penetration in Diabetic Patients With Wound Infections and Healthy Volunteers Via In Vivo Microdialysis (NCT NCT02620787)
NCT ID: NCT02620787
Last Updated: 2019-01-15
Results Overview
The ratio of tedizolid tissue concentrations to blood concentrations following the final tedizolid dose
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
48-72 hours
Results posted on
2019-01-15
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
6
|
|
Overall Study
COMPLETED
|
10
|
6
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Eligibility Criteria Not Met
|
1
|
0
|
Baseline Characteristics
Only patient participants were analysed for PEDIS grade. Healthy volunteers (i.e. non diabetics) did not exibit wound infections.
Baseline characteristics by cohort
| Measure |
Diabetic Wound Infection
n=10 Participants
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.
Tedizolid
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.
|
Healthy Volunteers
n=6 Participants
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.
Tedizolid
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.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 17 • n=10 Participants
|
33 years
STANDARD_DEVIATION 9 • n=6 Participants
|
44 years
STANDARD_DEVIATION 17 • n=16 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=10 Participants
|
3 Participants
n=6 Participants
|
8 Participants
n=16 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=10 Participants
|
3 Participants
n=6 Participants
|
8 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=10 Participants
|
0 Participants
n=6 Participants
|
8 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=10 Participants
|
6 Participants
n=6 Participants
|
8 Participants
n=16 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=10 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=10 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=10 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=10 Participants
|
1 Participants
n=6 Participants
|
1 Participants
n=16 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=10 Participants
|
5 Participants
n=6 Participants
|
15 Participants
n=16 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=10 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=10 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=16 Participants
|
|
Region of Enrollment
United States
|
10 Participants
n=10 Participants
|
6 Participants
n=6 Participants
|
16 Participants
n=16 Participants
|
|
Body Mass Index
|
31.5 kg/m^2
STANDARD_DEVIATION 6.3 • n=10 Participants
|
28.5 kg/m^2
STANDARD_DEVIATION 5.4 • n=6 Participants
|
30.4 kg/m^2
STANDARD_DEVIATION 6.0 • n=16 Participants
|
|
Weight
|
89.4 kg
STANDARD_DEVIATION 21 • n=10 Participants
|
79.5 kg
STANDARD_DEVIATION 17.9 • n=6 Participants
|
85.7 kg
STANDARD_DEVIATION 19.9 • n=16 Participants
|
|
Height
|
66.6 inches
STANDARD_DEVIATION 5.0 • n=10 Participants
|
65.7 inches
STANDARD_DEVIATION 4.5 • n=6 Participants
|
66.3 inches
STANDARD_DEVIATION 4.7 • n=16 Participants
|
|
Albumin
|
3.1 g/dL
STANDARD_DEVIATION 0.4 • n=10 Participants
|
4.6 g/dL
STANDARD_DEVIATION 0.3 • n=6 Participants
|
3.6 g/dL
STANDARD_DEVIATION 0.8 • n=16 Participants
|
|
Serum creatinine
|
0.9 mg/dL
STANDARD_DEVIATION 0.2 • n=10 Participants
|
0.9 mg/dL
STANDARD_DEVIATION 0.1 • n=6 Participants
|
0.9 mg/dL
STANDARD_DEVIATION 0.2 • n=16 Participants
|
|
Creatinine clearance
|
90.4 mg/ml
STANDARD_DEVIATION 31.9 • n=10 Participants
|
101.5 mg/ml
STANDARD_DEVIATION 26.6 • n=6 Participants
|
94.6 mg/ml
STANDARD_DEVIATION 29.6 • n=16 Participants
|
|
PEDIS Grade
Grade 2
|
1 Participants
n=10 Participants • Only patient participants were analysed for PEDIS grade. Healthy volunteers (i.e. non diabetics) did not exibit wound infections.
|
—
|
1 Participants
n=10 Participants • Only patient participants were analysed for PEDIS grade. Healthy volunteers (i.e. non diabetics) did not exibit wound infections.
|
|
PEDIS Grade
Grade 3
|
9 Participants
n=10 Participants • Only patient participants were analysed for PEDIS grade. Healthy volunteers (i.e. non diabetics) did not exibit wound infections.
|
—
|
9 Participants
n=10 Participants • Only patient participants were analysed for PEDIS grade. Healthy volunteers (i.e. non diabetics) did not exibit wound infections.
|
PRIMARY outcome
Timeframe: 48-72 hoursPopulation: One volunteer and one patient participant were excluded due to low concentrations
The ratio of tedizolid tissue concentrations to blood concentrations following the final tedizolid dose
Outcome measures
| Measure |
Diabetic Wound Infection
n=9 Participants
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.
|
Healthy Volunteers
n=5 Participants
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.
|
|---|---|---|
|
Tedizolid Tissue Penetration
|
0.98 ratio
Standard Deviation 0.43
|
0.82 ratio
Standard Deviation 0.08
|
SECONDARY outcome
Timeframe: 48-72 hoursPopulation: One volunteer and one patient participant were excluded due to low concentrations
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.
Outcome measures
| Measure |
Diabetic Wound Infection
n=9 Participants
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.
|
Healthy Volunteers
n=5 Participants
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.
|
|---|---|---|
|
Tedizolid Area Under the Curve (AUC) in Tissue
|
3.44 mg*h/L
Standard Deviation 1.50
|
5.20 mg*h/L
Standard Deviation 1.61
|
SECONDARY outcome
Timeframe: 48-72 hoursThe 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
Outcome measures
| Measure |
Diabetic Wound Infection
n=10 Participants
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.
|
Healthy Volunteers
n=6 Participants
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.
|
|---|---|---|
|
Tedizolid AUC in Plasma
|
18.47 mg*h/L
Standard Deviation 9.70
|
28.71 mg*h/L
Standard Deviation 9.58
|
Adverse Events
Diabetic Wound Infection
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Healthy Volunteers
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Diabetic Wound Infection
n=11 participants at risk
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.
|
Healthy Volunteers
n=6 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/11 • Adverse events were collected over a 76 hour window, from the start of first tedizolid dose (0 hour) to the end of blood/dialysate sampling (72 hours), plus a 4 hour observation window after the last sample was collected for subjects who received at least one dose of tedizolid. Note. In the diabetic wound infection group, 12 subjects were enrolled, but 11 received at least one dose. Therefore, the denominator is different from what is listed in the participant flow.
Adverse event: any pathologic or unintended change in the structure, function, or chemistry associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to do usual activities A serious adverse event will be defined as any which results in death or is immediately life-threatening, requires in-participant hospitalization.
|
50.0%
3/6 • Adverse events were collected over a 76 hour window, from the start of first tedizolid dose (0 hour) to the end of blood/dialysate sampling (72 hours), plus a 4 hour observation window after the last sample was collected for subjects who received at least one dose of tedizolid. Note. In the diabetic wound infection group, 12 subjects were enrolled, but 11 received at least one dose. Therefore, the denominator is different from what is listed in the participant flow.
Adverse event: any pathologic or unintended change in the structure, function, or chemistry associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to do usual activities A serious adverse event will be defined as any which results in death or is immediately life-threatening, requires in-participant hospitalization.
|
|
General disorders
Hypothermia
|
9.1%
1/11 • Adverse events were collected over a 76 hour window, from the start of first tedizolid dose (0 hour) to the end of blood/dialysate sampling (72 hours), plus a 4 hour observation window after the last sample was collected for subjects who received at least one dose of tedizolid. Note. In the diabetic wound infection group, 12 subjects were enrolled, but 11 received at least one dose. Therefore, the denominator is different from what is listed in the participant flow.
Adverse event: any pathologic or unintended change in the structure, function, or chemistry associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to do usual activities A serious adverse event will be defined as any which results in death or is immediately life-threatening, requires in-participant hospitalization.
|
0.00%
0/6 • Adverse events were collected over a 76 hour window, from the start of first tedizolid dose (0 hour) to the end of blood/dialysate sampling (72 hours), plus a 4 hour observation window after the last sample was collected for subjects who received at least one dose of tedizolid. Note. In the diabetic wound infection group, 12 subjects were enrolled, but 11 received at least one dose. Therefore, the denominator is different from what is listed in the participant flow.
Adverse event: any pathologic or unintended change in the structure, function, or chemistry associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to do usual activities A serious adverse event will be defined as any which results in death or is immediately life-threatening, requires in-participant hospitalization.
|
|
Gastrointestinal disorders
Nausea
|
9.1%
1/11 • Adverse events were collected over a 76 hour window, from the start of first tedizolid dose (0 hour) to the end of blood/dialysate sampling (72 hours), plus a 4 hour observation window after the last sample was collected for subjects who received at least one dose of tedizolid. Note. In the diabetic wound infection group, 12 subjects were enrolled, but 11 received at least one dose. Therefore, the denominator is different from what is listed in the participant flow.
Adverse event: any pathologic or unintended change in the structure, function, or chemistry associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to do usual activities A serious adverse event will be defined as any which results in death or is immediately life-threatening, requires in-participant hospitalization.
|
0.00%
0/6 • Adverse events were collected over a 76 hour window, from the start of first tedizolid dose (0 hour) to the end of blood/dialysate sampling (72 hours), plus a 4 hour observation window after the last sample was collected for subjects who received at least one dose of tedizolid. Note. In the diabetic wound infection group, 12 subjects were enrolled, but 11 received at least one dose. Therefore, the denominator is different from what is listed in the participant flow.
Adverse event: any pathologic or unintended change in the structure, function, or chemistry associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to do usual activities A serious adverse event will be defined as any which results in death or is immediately life-threatening, requires in-participant hospitalization.
|
Additional Information
Dr. David P. Nicolau
Center for Anti Infective Research and Development
Phone: (860) 972-3941
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place