Back to resultsStudy of Tedizolid Phosphate in Adolescents With Complicated Skin and Soft Tissue Infection (cSSTI) (MK-1986-012)
Primary Purpose
Skin Diseases, Infectious, Skin Diseases, Bacterial
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Tedizolid Phophate
Antibiotic comparator
Aztreonam
Metronidazole
Sponsored by
About this trial
This is an interventional treatment trial for Skin Diseases, Infectious
Eligibility Criteria
Inclusion Criteria:
- Males or females 12 years to <18 years
- Adequate venous access for IV administration of study drug for at least 24 hours (for participants receiving IV medication) and collection of protocol-specified blood samples
- Local symptoms must have started within 7 days before Study Day -1
- cSSTI meeting at least 1 of the clinical syndrome definitions.
- Suspected or documented Gram-positive infection from baseline Gram stain or culture.
- Parent/legally authorized representative (LAR) able to give informed consent and willing and able to comply with all required study procedures. Assent is also required of children who in the Investigator's judgment are capable of understanding the nature of the study
Exclusion Criteria:
- Uncomplicated minor skin and skin structure infections such as pustules, folliculitis, furuncles, minor abscesses (small volume of suppuration not surrounded by cellulitis/erysipelas), impetiginous lesions, superficial or limited cellulitis/erysipelas, and minor wound associated foreign body reactions (eg, stitch abscesses)
- Known bacteremia, severe sepsis or septic shock
- Recent history of opportunistic infections where the underlying cause of these infections is still active (eg, leukemia, transplant, acquired immunodeficiency syndrome)
- Hypersensitivity to tedizolid phosphate or any component in the formulation
- Hypersensitivity to all of the comparator drugs; hypersensitivity to a comparator drug does not preclude participation if an alternative comparator can be used
- For participants with wound infections: history of hypersensitivity to ceftazidime, aztreonam, or any component of the aztreonam formulation, if aztreonam adjunctive therapy is required; history of hypersensitivity to metronidazole or any component of the formulation, if metronidazole adjunctive therapy is required
- Needs oral administration of methotrexate, topotecan, irinotecan or rosuvastatin, during administration of oral study drug.
- Uses monoamine oxidase inhibitors, tricyclic antidepressants, buspirone, selective serotonin reuptake inhibitors and serotonin 5 hydroxytryptamine receptor agonists (triptans) within 14 days prior to study drug administration
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tedizolid Phosphate
Antibiotic comparator drug
Arm Description
Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events on Tedizolid Phosphate and Comparator Drugs
An adverse event (AE) refers to a treatment-emergent adverse event (TE-AE). A TE-AE is any AE that newly appeared, increased in frequency, or worsened in severity following initiation of study drug.
Secondary Outcome Measures
Number of Participants With Investigator's Assessment Indicating Clinical Success at Test of Cure (TOC) Visit (Intent to Treat Analysis Set)
Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.
Number of Participants With Investigator's Assessment Indicating Clinical Success at TOC Visit (Clinically Evaluable-Test of Cure [CE-TOC] Analysis Set)
Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.
Number of Participants With Early Clinical Responses Measured by Lesion Reduction
Early clinical response is defined as ≥20% reduction from baseline lesion area (defined as length multiplied by the width of the erythema, edema, and/or induration [EEI]) at the 48-72 hour (hr) visit.
Number of Participants With Investigator's Assessment Indicating Clinical Success at End of Therapy (EOT) Visit (Intent to Treat Analysis Set)
Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.
Number of Participants With Investigator's Assessment Indicating Clinical Success at EOT Visit (Clinically Evaluable-End of Therapy [CE-EOT] Analysis Set)
Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2) absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.
Full Information
NCT ID
NCT02276482
First Posted
October 9, 2014
Last Updated
July 12, 2019
Sponsor
Cubist Pharmaceuticals LLC
1. Study Identification
Unique Protocol Identification Number
NCT02276482
Brief Title
Study of Tedizolid Phosphate in Adolescents With Complicated Skin and Soft Tissue Infection (cSSTI) (MK-1986-012)
Official Title
Phase 3 Study of IV to Oral 6-Day Tedizolid Phosphate Compared With 10-day Comparator in Subjects 12 to < 18 Years With cSSTI.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
March 25, 2015 (Actual)
Primary Completion Date
September 17, 2018 (Actual)
Study Completion Date
September 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cubist Pharmaceuticals LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to compare the safety of intravenous (IV) and/or oral 6-day 200 mg tedizolid phosphate with 10-day comparator in participants 12 to <18 years with cSSTI.
Detailed Description
A randomized, single-blind, multicenter, Phase 3 study of IV and/or oral tedizolid phosphate 200 mg once per day for 6 days compared with IV and/or oral comparator for 10 days for the treatment of cSSTI, also known as acute bacterial skin and skin structure infections, in participants 12 to <18 years. cSSTI includes major cutaneous abscess, cellulitis/erysipelas, and wound infection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Skin Diseases, Infectious, Skin Diseases, Bacterial
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tedizolid Phosphate
Arm Type
Experimental
Arm Description
Tedizolid Phosphate IV and/or oral 200 mg once per day for 6 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Arm Title
Antibiotic comparator drug
Arm Type
Active Comparator
Arm Description
IV and/or oral antibiotic comparator drug for 10 days. Participants with gram-negative wound infection may receive aztreonam (IV) and/or metronidazole (IV or oral).
Intervention Type
Drug
Intervention Name(s)
Tedizolid Phophate
Other Intervention Name(s)
TR701-122, MK-1986, SIVEXTRO®
Intervention Description
Tedizolid Phophate 200 mg, IV and/or oral for 6 days
Intervention Type
Drug
Intervention Name(s)
Antibiotic comparator
Other Intervention Name(s)
Vancomycin: Vancocin, Firvanq, Lyphocin; Linezolid: Zyvox; Clindamycin: Cleocin; Flucloxacillin: Floxapen, Flopen, Staphylex; Cefazolin: Ancef, Kefzol; Cephalexin: Keflex, Zartan, Panixine, Biocef
Intervention Description
Antibiotic comparator drug, IV and/or orally for 10 days. Antibiotic comparator included the following: Vancomycin, Linezolid, Clindamycin, Flucloxacillin, Cefazolin, Cephalexin.
Intervention Type
Drug
Intervention Name(s)
Aztreonam
Other Intervention Name(s)
Azactam, Cayston
Intervention Description
In countries and/or sites where aztreonam is available, adjunctive aztreonam (IV) may be initiated on Day 1 or during the first 3 days of treatment if the participant is determined or suspected to have an infection with gram-negative aerobic pathogens.
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Other Intervention Name(s)
Flagyl, Metro
Intervention Description
Metronidazole (IV or oral) may be initiated on Day 1 or during the first 3 days of treatment if the participant is determined or suspected to have an infection with anaerobic pathogens.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events on Tedizolid Phosphate and Comparator Drugs
Description
An adverse event (AE) refers to a treatment-emergent adverse event (TE-AE). A TE-AE is any AE that newly appeared, increased in frequency, or worsened in severity following initiation of study drug.
Time Frame
Up to 40 days (including 30-day follow-up)
Secondary Outcome Measure Information:
Title
Number of Participants With Investigator's Assessment Indicating Clinical Success at Test of Cure (TOC) Visit (Intent to Treat Analysis Set)
Description
Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.
Time Frame
TOC Visit: 18-25 days after first drug infusion
Title
Number of Participants With Investigator's Assessment Indicating Clinical Success at TOC Visit (Clinically Evaluable-Test of Cure [CE-TOC] Analysis Set)
Description
Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.
Time Frame
TOC Visit: 18-25 days after first drug infusion
Title
Number of Participants With Early Clinical Responses Measured by Lesion Reduction
Description
Early clinical response is defined as ≥20% reduction from baseline lesion area (defined as length multiplied by the width of the erythema, edema, and/or induration [EEI]) at the 48-72 hour (hr) visit.
Time Frame
48-72 hr after first drug infusion
Title
Number of Participants With Investigator's Assessment Indicating Clinical Success at End of Therapy (EOT) Visit (Intent to Treat Analysis Set)
Description
Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2)absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.
Time Frame
EOT Visit: up to 13 days after first drug infusion
Title
Number of Participants With Investigator's Assessment Indicating Clinical Success at EOT Visit (Clinically Evaluable-End of Therapy [CE-EOT] Analysis Set)
Description
Investigator's assessment of clinical success is defined as (1) resolution or near resolution of most disease-specific signs and symptoms, (2) absence or near resolution of regional or systemic signs of infection (lymphadenopathy, fever, >10% immature neutrophils, abnormal white blood cell count), if present at baseline, and (3) no new signs, symptoms, or complications attributable to the infection under study so no further antibiotic therapy is required for the treatment of the primary lesion.
Time Frame
EOT Visit: up to 13 days after first drug infusion
Other Pre-specified Outcome Measures:
Title
Change From Baseline in Lesion Size
Description
Lesion size is the area in cm^2 of erythema, edema or induration. A negative number corresponds to a decrease in lesion size.
Time Frame
Baseline and TOC visit (18 to 25 days after infusion)
Title
Peak Plasma Concentration (Cmax) of Tedizolid
Description
The Cmax of tedizolid in plasma after the last dose was estimated based on population pharmacokinetic analysis of observed pharmacokinetic data. Blood samples were collected for pharmacokinetic analysis at specific time points.
Time Frame
Day 1 at 5-80 minutes (min) and 4-12 hrs post-infusion or 2 samples collected between 4-12 hrs after oral dose, at least 60 min apart; at 48-72 hrs: within 60 min prior to administration and 4-12 hrs after administration; and anytime between Day 7 and 9
Title
Area Under the Plasma Concentration Versus Time Curve Time 0 to 24 Hours (AUC0-24h) of Tedizolid
Description
AUC0-24h is a measure of the total tedizolid exposure in the plasma from the dose to 24 hours after last dose. AUC0-24h was estimated based on population pharmacokinetic analysis of observed pharmacokinetic data. Blood samples were collected for pharmacokinetic analysis at specific time points.
Time Frame
Day 1 at 5-80 min and 4-12 hrs post-infusion or 2 samples collected between 4-12 hrs after oral dose, at least 60 min apart; at 48-72 hrs: within 60 min prior to administration and 4-12 hrs after administration; and anytime between Day 7 and 9
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females 12 years to <18 years
Adequate venous access for IV administration of study drug for at least 24 hours (for participants receiving IV medication) and collection of protocol-specified blood samples
Local symptoms must have started within 7 days before Study Day -1
cSSTI meeting at least 1 of the clinical syndrome definitions.
Suspected or documented Gram-positive infection from baseline Gram stain or culture.
Parent/legally authorized representative (LAR) able to give informed consent and willing and able to comply with all required study procedures. Assent is also required of children who in the Investigator's judgment are capable of understanding the nature of the study
Exclusion Criteria:
Uncomplicated minor skin and skin structure infections such as pustules, folliculitis, furuncles, minor abscesses (small volume of suppuration not surrounded by cellulitis/erysipelas), impetiginous lesions, superficial or limited cellulitis/erysipelas, and minor wound associated foreign body reactions (eg, stitch abscesses)
Known bacteremia, severe sepsis or septic shock
Recent history of opportunistic infections where the underlying cause of these infections is still active (eg, leukemia, transplant, acquired immunodeficiency syndrome)
Hypersensitivity to tedizolid phosphate or any component in the formulation
Hypersensitivity to all of the comparator drugs; hypersensitivity to a comparator drug does not preclude participation if an alternative comparator can be used
For participants with wound infections: history of hypersensitivity to ceftazidime, aztreonam, or any component of the aztreonam formulation, if aztreonam adjunctive therapy is required; history of hypersensitivity to metronidazole or any component of the formulation, if metronidazole adjunctive therapy is required
Needs oral administration of methotrexate, topotecan, irinotecan or rosuvastatin, during administration of oral study drug.
Uses monoamine oxidase inhibitors, tricyclic antidepressants, buspirone, selective serotonin reuptake inhibitors and serotonin 5 hydroxytryptamine receptor agonists (triptans) within 14 days prior to study drug administration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
33395210
Citation
Bradley JS, Antadze T, Ninov B, Tayob MS, Broyde N, Butterton JR, Chou MZ, De Anda CS, Kim JY, Sears PS. Safety and Efficacy of Oral and/or Intravenous Tedizolid Phosphate From a Randomized Phase 3 Trial in Adolescents With Acute Bacterial Skin and Skin Structure Infections. Pediatr Infect Dis J. 2021 Mar 1;40(3):238-244. doi: 10.1097/INF.0000000000003010.
Results Reference
derived
Learn more about this trial
Study of Tedizolid Phosphate in Adolescents With Complicated Skin and Soft Tissue Infection (cSSTI) (MK-1986-012)
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