Clinical trial NCT02276482: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Skin Diseases, Infectious
Skin Diseases, Bacterial
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2014-10-28
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Adverse Events on Tedizolid Phosphate and Comparator Drugs
timeFrame: Up to 40 days (including 30-day follow-up)
Secondary outcomes:
measure: Number of Participants With Investigator's Assessment Indicating Clinical Success at Test of Cure (TOC) Visit (Intent to Treat Analysis Set)
timeFrame: TOC Visit: 18-25 days after first drug infusion
measure: Number of Participants With Investigator's Assessment Indicating Clinical Success at TOC Visit (Clinically Evaluable-Test of Cure [CE-TOC] Analysis Set)
timeFrame: TOC Visit: 18-25 days after first drug infusion
measure: Number of Participants With Early Clinical Responses Measured by Lesion Reduction
timeFrame: 48-72 hr after first drug infusion
measure: Number of Participants With Investigator's Assessment Indicating Clinical Success at End of Therapy (EOT) Visit (Intent to Treat Analysis Set)
timeFrame: EOT Visit: up to 13 days after first drug infusion
measure: Number of Participants With Investigator's Assessment Indicating Clinical Success at EOT Visit (Clinically Evaluable-End of Therapy [CE-EOT] Analysis Set)
timeFrame: EOT Visit: up to 13 days after first drug infusion
Other outcomes:
measure: Change From Baseline in Lesion Size
timeFrame: Baseline and TOC visit (18 to 25 days after infusion)
measure: Peak Plasma Concentration (Cmax) of Tedizolid
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve Time 0 to 24 Hours (AUC0-24h) of Tedizolid
timeFrame: 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
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.