A Study of Safety and Efficacy of MK-1986 (Tedizolid Phosphate) and Comparator in Participants From Birth to Less Than 12 Years of Age With Acute Bacterial Skin and Skin Structure Infections (MK-1986-018)

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, and efficacy of tedizolid phosphate (MK-1986) compared with comparator antibacterial agent in participants from birth to less than 12 years of age with acute bacterial skin and skin structure infections (ABSSSI).

Detailed Description
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Participants will be randomized (3:1) to receive tedizolid phosphate at a weight-based dose ≤200 mg/day, intravenous (IV) and/or oral suspension for 6 to 10 days, or comparator IV and/or oral per local standard of care for 10 to 14 days. The switch from IV to oral administration can be made at any time based on 1) no worsening of the primary skin lesion, 2) last temperature <37.7 °C, and 3) primary acute bacterial skin and skin structure infection (ABSSSI) site has not worsened and at least 1 site has improved from Baseline. The potential 4-day treatment extension will be based on clinical need as judged by the investigator, considering the following criteria: 1) ≥40% reduction in primary lesion size, 2) reduction in pain, and 3) no new signs and symptoms and no complications attributable to ABSSSI compared with Baseline.

Official Title
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A Phase III Randomized, Active-comparator-Controlled Clinical Trial to Study the Safety and Efficacy of MK-1986 (Tedizolid Phosphate) and Comparator, in Subjects From Birth to Less Than 12 Years of Age With Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Conditions
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Acute Bacterial Skin and Skin Structure Infections

Intervention / Treatment
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* Drug: Tedizolid phosphate
* Drug: Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a parent/legally acceptable representative who is able to give documented informed consent Has ABSSSI, defined as ≥1 of the following: 1) cellulitis/erysipelas, 2) major cutaneous abscess, or 3) wound infection Local symptoms of ABSSSI that started within 14 days before study start Suspected or documented Gram-positive bacterial infection Body weight ≥3.2 kg Exclusion Criteria: Uncomplicated skin and skin structure infection ABSSSI due to or associated with disallowed etiology per protocol Received antibacterial therapy for treatment of the current episode of ABSSSI except 1) <48 hours of antibacterial therapy with a short-acting antibacterial drug, or 2) response is considered to be failure (no improvement in signs and symptoms) after at least 48 hours of therapy Known bacteremia, severe sepsis, or septic shock Significant or life-threatening condition, disease, or organ system condition Recent history of opportunistic infections where the underlying cause of the infection is still active, or is suspected to be at risk of opportunistic infection with unusual pathogens Received or is receiving treatment for active tuberculosis within 1 month of study start Known or suspected severe neutropenia Human immunodeficiency virus (HIV) positive and has Cluster of Differentiation (CD) 4 cell count <15% (HIV testing is not required for eligibility) Renal impairment that requires renal filtration Severe hepatic impairment Cardiac or electrocardiogram (ECG) finding that would limit participation in the study Received an investigational medicinal product (not approved) within 30 days before study start Investigational device present or removed within 30 days before study start Previously treated with tedizolid phosphate Contraindication, including hypersensitivity to tedizolid phosphate, other oxazolidinones, or any component in the formulation Contraindication, including hypersensitivity to all available comparator drugs Wound infection and history of hypersensitivity to aztreonam adjunctive therapy or metronidazole adjunctive therapy, if adjunctive therapy is required Needs oral administration of methotrexate, topotecan, irinotecan, or rosuvastatin, during administration of oral study drug (administration during the follow-up period, ie, after the EOT visit, is allowed, as is administration during treatment with IV drug) Female who is pregnant or nursing or is of childbearing potential and not abstinent; or male who is not abstinent Use of monoamine oxidase inhibitors, tricyclic antidepressants, buspirone, selective serotonin reuptake inhibitors, or serotonin 5-hydroxytryptamine receptor agonists (triptans) Identified as having used illicit drugs (urine drug screening not required for entry)

Ages Eligible for Study
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Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Tedizolid phosphate 6 to <12 Years<br>Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days. | Drug: Tedizolid phosphate<br>* Tedizolid phosphate IV solution or oral suspension<br>* Other names: TR-701 FA;|
| Active Comparator: Cohort 1 Comparator: 6 to <12 Years<br>Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days | Drug: Comparator<br>* Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care<br>|
| Experimental: Cohort 2: Tedizolid phosphate 2 to <6 Years<br>Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days. | Drug: Tedizolid phosphate<br>* Tedizolid phosphate IV solution or oral suspension<br>* Other names: TR-701 FA;|
| Active Comparator: Cohort 2 Comparator: 2 to <6 Years<br>Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days | Drug: Comparator<br>* Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care<br>|
| Experimental: Cohort 3: Tedizolid phosphate 28 Days to <2 Years<br>Participants will receive tedizolid phosphate once-daily single 200-mg dose (body weight ≥50 kg) or twice-daily 2-mg/kg doses (body weight 30 kg to <50 kg); or twice-daily 2.5-mg/kg doses (body weight 3.2 kg to <30 kg), by IV and/or oral suspension for 6 to 10 days. | Drug: Tedizolid phosphate<br>* Tedizolid phosphate IV solution or oral suspension<br>* Other names: TR-701 FA;|
| Active Comparator: Cohort 3: Comparator: 28 Days to <2 Years<br>Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days | Drug: Comparator<br>* Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care<br>|
| Experimental: Cohort 4: Tedizolid phosphate Birth to <28 Days Neonates<br>Participants will receive tedizolid phosphate ≤200 mg daily dose, IV and/or oral suspension for 6 to 10 days. Exact mg/kg dose is to be determined based on results of another study covering the age range. | Drug: Tedizolid phosphate<br>* Tedizolid phosphate IV solution or oral suspension<br>* Other names: TR-701 FA;|
| Active Comparator: Comparator: Birth to <28 Days (Term and preterm neonates)<br>Participants will receive comparator IV and/or oral per local standard of care for 10 to14 days | Drug: Comparator<br>* Vancomycin IV, linezolid IV or oral (outside European Union only), clindamycin IV or oral, flucloxacillin IV or oral, cefazolin IV, or cephalexin oral provided locally by the trial site and administered per local standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with ≥1 adverse events (AEs) | An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants with one or more AEs will be reported. | Up to Day 35 | 
| Percentage of participants discontinuing from study therapy due to AEs | An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants discontinued from the study due to an AE will be reported. | Up to Day 35 | 
| Percentage of participants with hematopoietic cytopenias | A standardized MedDRA query for hematopoietic cytopenia will be conducted. The percentage of participants with a hematopoietic cytopenia will be reported. | Up to Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with clinical success | The investigator's assessment of clinical response will be conducted at the Test of Cure (TOC) visit, approximately 25 days after the first infusion. Clinical success is defined as 1) resolution or near-resolution of most signs and symptoms, 2) absence or near-resolution of signs of infection, and 3) no new signs, symptoms, or complications attributable to the infections (no further antibiotic therapy required for the primary lesion). The percentage of participants with clinical success will be reported. | Day 25 |