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Study 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
Cubist Pharmaceuticals LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Skin Diseases, Infectious

Eligibility Criteria

12 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

    First Posted
    October 9, 2014
    Last Updated
    July 12, 2019
    Sponsor
    Cubist Pharmaceuticals LLC
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    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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