A Pharmacokinetic Study of Tedizolid Phosphate in Pediatric Participants With Gram-Positive Infections (MK-1986-014)

Study Overview
=================
Brief Summary
-----------------
The primary objectives of this study are to describe the single-dose, and multiple dose pharmacokinetics (PK) of intravenous (IV) tedizolid phosphate, or a single dose oral suspension of tedizolid phosphate, when administered to pediatric participants, full-term neonates, and preterm neonates.

Official Title
-----------------
A Phase 1, Single- and Multiple-Dose Safety and Pharmacokinetic Study of Oral and IV Tedizolid Phosphate (MK-1986) in Inpatients Under 2 Years Old

Conditions
-----------------
Gram-Positive Infections

Intervention / Treatment
-----------------
* Drug: IV Tedizolid Phosphate
* Drug: Oral Suspension Tedizolid Phosphate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is receiving prophylaxis for or has a confirmed or suspected infection with gram-positive bacteria and receiving concurrent antibiotic treatment with gram -positive antibacterial activity. Is at least 1 kg in weight. Is in stable condition as determined from medical history, physical examination, electrocardiogram (ECG), vital signs, and clinical laboratory evaluations. Has no clinically significant ECG abnormalities. Has sufficient vascular access to receive trial drug, and allow for required blood draws. Is able to receive medication by mouth, for those dosed with oral suspension; dose administration via feeding tube is acceptable. Exclusion Criteria: Has a history of seizures, other than febrile seizures, clinically significant cardiac arrhythmia or condition, moderate or severe renal impairment, or any physical condition that could interfere with the interpretation of the study results, as determined by the Investigator. Has used rifampin within 14 days prior to dosing. Has used or will be using proton pump inhibitors, H2 blockers, or antacids (for participants in Part B, i.e, oral suspension dose) at any time from 24 hours prior to dosing through 24 hours after dosing.. Has a recent (3-month) history or current infection with viral hepatitis or other significant hepatic disease. Has a history of drug allergy or hypersensitivity to oxazolidinones. Has had significant blood loss. Need for oral administration of topotecan, rosuvastatin, irinotecan, or methotrexate during administration of oral study drug. Used monoamine oxidase inhibitors (MAOIs) or serotonergic agents including tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and serotonin 5-hydroxytryptamine receptor agonists (triptans), meperidine, or buspirone within 14 days prior to study, or planned use while on study. Has received another investigational product within the 30 days prior to enrollment.

Ages Eligible for Study
-----------------
Minimum Age: 1 Day
Maximum Age: 24 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV Tedizolid Phosphate<br>A single dose, or twice daily dose for 3 days, of tedizolid phosphate administered intravenously (IV). For body weight <10 kg: 3 mg/kg; for body weight 10 to <30 kg: 2.5 mg/kg. | Drug: IV Tedizolid Phosphate<br>* A single dose, or twice daily dose for 3 days, of tedizolid phosphate administered IV.<br>|
| Experimental: Oral Suspension Tedizolid Phosphate<br>A single dose of tedizolid phosphate administered as an oral suspension. For body weight <10 kg: 3 mg/kg; for body weight 10 to <30 kg: 2.5 mg/kg. | Drug: Oral Suspension Tedizolid Phosphate<br>* A single dose of tedizolid phosphate administered as an oral suspension.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-last of tedizolid phosphate | Area under the concentration-time curve from time 0 to time of last quantifiable drug concentration (AUC0-last) of plasma tedizolid phosphate | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| AUC0-inf of tedizolid phosphate | Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of plasma tedizolid phosphate | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| Cmax of tedizolid phosphate | Maximum concentration (Cmax) of plasma tedizolid phosphate | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| Tmax of tedizolid phosphate | Time to reach Cmax (Tmax) of plasma tedizolid phosphate | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| T1/2 of tedizolid phosphate | Apparent terminal half-life (t1/2) of plasma tedizolid phosphate | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| AUC0-last of tedizolid | Area under the concentration-time curve from time 0 to time of last quantifiable drug concentration of plasma tedizolid | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| AUC0-inf of tedizolid | Area under the concentration-time curve from time 0 to infinity of plasma tedizolid | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| Cmax of tedizolid | Maximum concentration of plasma tedizolid | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| Tmax of tedizolid | Time to reach Cmax of plasma tedizolid | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 
| T1/2 of tedizolid | Apparent terminal half-life of plasma tedizolid | IV Treatment: after the end of infusion, 1.5, 3, 6, 12, 24 hours after the start of infusion; Oral Suspension Treatment: 1, 3, 5, 8, 12, and 24 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) | Number of participants with one or more adverse events. | Up to Day 21 | 
| Discontinuations | Number of participants who discontinued from study due to an AE | Day 1 |