A Study of Oral and Intravenous (IV) Tedizolid Phosphate in Hospitalized Participants, Ages 2 to <12 Years, With Confirmed or Suspected Bacterial Infection (MK-1986-013)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Gram-Positive Bacterial Infections

Treatments: Drug: Tedizolid Phosphate (IV); Drug: Tedizolid Phosphate (oral suspension)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02750761

1986-013

TR701-120 (Other Identifier)

MK-1986-013 (Other Identifier)

2015-004595-29 (EudraCT Number)

Details and patient eligibility

About

This is a study to assess the pharmacokinetics (PK) of tedizolid phosphate and its active metabolite, tedizolid, and the safety of tedizolid phosphate following administration of a single IV (Part A) or oral suspension (Part B) administration to hospitalized participants ages 6 to <12 years (Groups 1 and 3, respectively), and 2 to <6 years (Groups 2 and 4, respectively).

Full description

Part A (IV):

• Group 1 (Cohort 1 and Cohort 2) (6 to <12 years)
• Group 2 (Cohort 1 and Cohort 2) (2 to <6 years)

Part B (Oral Suspension):

• Group 3 (6 to <12 years)
• Group 4 (2 to <6 years)

In Cohort 1 of Group 1 (IV) participants received a single administration of tedizolid phosphate at 5 mg/kg of total body weight. After all participants in Cohort 1 of Group 1 received study drug, a preliminary analysis of the safety and PK data was performed and results were used to select 4 mg/kg as the appropriate dose for Cohort 2 of Group 1 and Group 3, and to select 6 mg/kg as the starting dose for the younger participants, Cohort 1 of Group 2. After all participants in Cohort 1 of Group 2 receive study drug, another preliminary analysis of the safety and PK data will be performed and results will be used to confirm 6 mg/kg as the appropriate dose for Cohort 2 of Group 2. Similarly, the Group 4 dose will be confirmed after data review of Group 3 results.

Enrollment: 32 patients

Sex: All

Ages: 2 to 11 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Receiving prophylaxis for or with a confirmed or suspected infection with Gram-positive bacteria and receiving concurrent antibiotic treatment with Gram-positive antibacterial activity;
• Weight >5th percentile and <95th percentile based on age;
• Stable condition as determined from medical history, physical examination, minimally 5-lead electrocardiogram (ECG), vital signs, and clinical laboratory evaluations;
• Females must be premenarchal, abstinent, or practicing an effective method of birth control;

Exclusion criteria

• History of seizures, other than febrile seizures, clinically significant cardiac arrhythmia, cystic fibrosis, moderate or severe renal impairment, or any physical condition that could interfere with the study results;
• Recent (3 month) history or current infection with viral hepatitis or other significant hepatic disease;
• History of drug allergy or hypersensitivity to oxazolidinones;
• Pregnant or breast feeding;
• Significant blood loss within 60 days prior to study start;
• Any acute or chronic condition that would limit the participant's ability to complete and/or participate in this clinical study.
• Treatment with investigational medicinal product within 30 days before the infusion/dose of study drug.
• Oral administration of methotrexate, topotecan, irinotecan or rosuvastatin, during administration of oral study drug. Administration during the follow-up period is allowed, as is administration during treatment with IV study drug.
• Use of monoamine oxidase inhibitors or serotonergic agents including tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin 5 hydroxytryptamine receptor agonists (triptans), meperidine, or buspirone within,14 days prior to study, or planned use while on study.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 6 patient groups

Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 years)

Experimental group

Description:

Participants 6 to \<12 years of age received a single intravenous infusion of tedizolid phosphate dosed at 5 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.

Treatment:

Drug: Tedizolid Phosphate (IV)

Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 years)

Experimental group

Description:

Participants 6 to \<12 years of age received a single intravenous infusion of tedizolid phosphate dosed at 4 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.

Treatment:

Drug: Tedizolid Phosphate (IV)

Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 years)

Experimental group

Description:

Participants 2 to \<6 years of age received a single intravenous infusion of tedizolid phosphate dosed at 6 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.

Treatment:

Drug: Tedizolid Phosphate (IV)

Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 years)

Experimental group

Description:

Participants 2 to \<6 years of age received a single intravenous infusion of tedizolid phosphate dosed at 3 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.

Treatment:

Drug: Tedizolid Phosphate (IV)

Group 3: Tedizolid oral 4 mg/kg (6 to <12 years)

Experimental group

Description:

Participants 6 to \<12 years of age received a single dose of tedizolid phosphate oral suspension dosed at 4 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.

Treatment:

Drug: Tedizolid Phosphate (oral suspension)

Group 4: Tedizolid oral 3 mg/kg (2 to <6 years)

Experimental group

Description:

Participants 2 to \<6 years of age received a single dose of tedizolid phosphate oral suspension dosed at 3 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate.

Treatment:

Drug: Tedizolid Phosphate (oral suspension)