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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Acute Bacterial Skin and Skin Structure Infections

Treatments: Drug: Tedizolid phosphate; Drug: Comparator

Study type: Interventional

Funder types: Industry

Identifiers

NCT03176134

1986-018

MK-1986-018 (Other Identifier)

2016-003884-20 (EudraCT Number)

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 100 patients

Sex: All

Ages: 1 day to 11 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a parent/legally acceptable representative who is able to give documented informed consent
• Has acute bacterial skin and skin structure infections (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

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 end of treatment (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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 8 patient groups

Cohort 1: Tedizolid phosphate 6 to <12 Years

Experimental group

Description:

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.

Treatment:

Drug: Tedizolid phosphate

Cohort 1: Comparator 6 to <12 Years

Active Comparator group

Description:

Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days.

Treatment:

Drug: Comparator

Cohort 2: Tedizolid phosphate 2 to <6 Years

Experimental group

Description:

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.

Treatment:

Drug: Tedizolid phosphate

Cohort 2: Comparator 2 to <6 Years

Active Comparator group

Description:

Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days.

Treatment:

Drug: Comparator

Cohort 3: Tedizolid phosphate 28 Days to <2 Years

Experimental group

Description:

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.

Treatment:

Drug: Tedizolid phosphate

Cohort 3: Comparator 28 Days to <2 Years

Active Comparator group

Description:

Participants will receive comparator IV and/or oral per local standard of care for 10 to 14 days.

Treatment:

Drug: Comparator

Cohort 4: Tedizolid phosphate Birth to <28 Days Term and Preterm Neonates

Experimental group

Description:

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 (NCT03217565) covering the age range.

Treatment:

Drug: Tedizolid phosphate

Cohort 4: Comparator Birth to <28 Days Term and Preterm Neonates

Active Comparator group

Description:

Participants will receive comparator IV and/or oral per local standard of care for 10 to14 days.

Treatment:

Drug: Comparator