Study of Tedizolid Phosphate in Adolescents With Complicated Skin and Soft Tissue Infection (cSSTI) (MK-1986-012)

Phase 3 Study of IV to Oral 6-Day Tedizolid Phosphate Compared With 10-day Comparator in Subjects 12 to < 18 Years With cSSTI.

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.

Study Overview

• Status: Completed
• Conditions: Skin Diseases, Infectious; Skin Diseases, Bacterial
• Intervention / Treatment: Drug: Tedizolid Phophate; Drug: Aztreonam; Drug: Metronidazole; Drug: Antibiotic comparator

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tedizolid Phosphate; 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).	Drug: Tedizolid Phophate; Tedizolid Phophate 200 mg, IV and/or oral for 6 days; Other Names: SIVEXTRO®; MK-1986; TR701-122; Drug: Aztreonam; 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.; Other Names: Azactam, Cayston; Drug: Metronidazole; 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.; Other Names: Flagyl, Metro
Active Comparator: Antibiotic comparator drug; 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).	Drug: Aztreonam; 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.; Other Names: Azactam, Cayston; Drug: Metronidazole; 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.; Other Names: Flagyl, Metro; Drug: Antibiotic comparator; Antibiotic comparator drug, IV and/or orally for 10 days. Antibiotic comparator included the following: Vancomycin, Linezolid, Clindamycin, Flucloxacillin, Cefazolin, Cephalexin.; Other Names: Vancomycin: Vancocin, Firvanq, Lyphocin; Linezolid: Zyvox; Clindamycin: Cleocin; Flucloxacillin: Floxapen, Flopen, Staphylex; Cefazolin: Ancef, Kefzol; Cephalexin: Keflex, Zartan, Panixine, Biocef

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 40 days (including 30-day follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	TOC Visit: 18-25 days after first drug infusion
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.	TOC Visit: 18-25 days after first drug infusion
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.	48-72 hr after first drug infusion
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.	EOT Visit: up to 13 days after first drug infusion
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.	EOT Visit: up to 13 days after first drug infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Lesion Size	Lesion size is the area in cm^2 of erythema, edema or induration. A negative number corresponds to a decrease in lesion size.	Baseline and TOC visit (18 to 25 days after infusion)
Peak Plasma Concentration (Cmax) of Tedizolid	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.	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
Area Under the Plasma Concentration Versus Time Curve Time 0 to 24 Hours (AUC0-24h) of Tedizolid	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.	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

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2015
• Primary Completion (Actual): September 17, 2018
• Study Completion (Actual): September 17, 2018

Study Registration Dates

• First Submitted: October 9, 2014
• First Submitted That Met QC Criteria: October 27, 2014
• First Posted (Estimate): October 28, 2014

Study Record Updates

• Last Update Posted (Actual): August 7, 2019
• Last Update Submitted That Met QC Criteria: July 12, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Skin Diseases, Infectious; Skin Diseases; Skin Diseases, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Vancomycin; Linezolid; Metronidazole; Anti-Bacterial Agents; Clindamycin; Cefazolin; Cephalexin; Aztreonam; Tedizolid
• Other Study ID Numbers: 1986-012; TR701-122 (Other Identifier: Cubist Pharmaceuticals LLC Protocol Number); 2014-004023-40 (EudraCT Number); MK-1986-012 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No