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

Merck Sharp & Dohme LLC47 enrolled

Overview

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.

Per protocol, PK analysis in Part A Group 1 will be conducted across ages in Cohorts 1 and 2 combined: Part A Group 1 Cohort 1 + Cohort 2: 28 days to \<24 months.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gram-Positive Infections

Interventions

IV Tedizolid PhosphateDRUG

A single dose, or twice daily dose for 3 days, of tedizolid phosphate administered IV.

Oral Suspension Tedizolid PhosphateDRUG

A single dose of tedizolid phosphate administered as an oral suspension.

Eligibility

Sex: ALLMin age: 1 DayMax age: 24 Months

Medical Language ↔ Plain English

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.

Locations (30)

Outcomes

Primary Outcomes

Part A: Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Drug Concentration (AUC0-last) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration

AUC0-last of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of pharmacokinetic (PK) outcomes in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, tedizolid phosphate AUC0-last for multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration

AUC0-inf of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK outcomes in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, tedizolid phosphate AUC0-inf for multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: Maximum Concentration (Cmax) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration

Cmax of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK outcomes in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, tedizolid phosphate Cmax for multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Data from ClinicalTrials.gov

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Arkansas Children's Hospital ( Site 1012)

Little Rock, Arkansas, United States

Children's Hospital of Orange County ( Site 1001)

Orange, California, United States

Sharp Memorial Hospital ( Site 1021)

San Diego, California, United States

Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1022)

Chicago, Illinois, United States

Our Lady of the Lake Regional Medical Center. ( Site 1004)

Baton Rouge, Louisiana, United States

Saint Louis Children's Hospital ( Site 1020)

St Louis, Missouri, United States

Primary Children's Hospital ( Site 1000)

Salt Lake City, Utah, United States

Medical Center - 1- Sevlievo EOOD ( Site 2207)

Sevlievo, Gabrovo, Bulgaria

MHAT Sv. Ivan Rilski EOOD ( Site 2201)

Kozloduy, Vratsa, Bulgaria

UMHAT Deva Maria ( Site 2208)

Burgas, Bulgaria

...and 20 more locations

Part A: Time to Reach Maximum Concentration (Tmax) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration

Tmax of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK outcomes in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, tedizolid phosphate Tmax for multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: Apparent Terminal Half-life (t½) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration

t½ of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK outcomes in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, tedizolid phosphate t½ for multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: AUC0-last of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration

AUC0-last of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. As specified in the protocol, tedizolid phosphate AUC0-last for single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol. Participants in Group 2 Cohort 2 study arm did not meet the criteria for PK per protocol analysis population for this outcome and were excluded from this protocol-specified analysis.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: AUC0-inf of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration

AUC0-inf of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. As specified in the protocol, tedizolid phosphate AUC0-inf for single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol. Participants in Group 2 Cohort 2 study arm did not meet the criteria for PK per protocol analysis population for this endpoint and were excluded from this protocol-specified analysis.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: Cmax of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration

Cmax of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. As specified in the protocol, tedizolid phosphate Cmax for single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol. Participants in Group 2 Cohort 2 study arm did not meet the criteria for PK per protocol analysis population for this outcome and were excluded from this protocol-specified analysis.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: Tmax of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration

Tmax of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. As specified in the protocol, tedizolid phosphate Tmax for single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol. Participants in Group 2 Cohort 2 study arm did not meet the criteria for PK per protocol analysis population for this outcome and were excluded from this protocol-specified analysis.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: t½ of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration

t½ of tedizolid phosphate was quantified in participants receiving tedizolid phosphate. As specified in the protocol, tedizolid phosphate t½ for single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1) were not included in this outcome and have been reported separately in the record. Tedizolid phosphate PK analysis was not planned or conducted in Part B (Groups 4, 5, 6), per protocol. Participants in Group 2 Cohort 2 study arm did not meet the criteria for PK per protocol analysis population for this outcome and were excluded from this protocol-specified analysis.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: AUC0-24 of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate [AUC0-last]

AUC0-last of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK endpoints in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, AUC0-last for tedizolid metabolite in multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) and Part B (Groups 4, 5, 6) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: AUC0-inf of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate

AUC0-inf of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK endpoints in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, AUC0-inf for tedizolid metabolite in multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) and Part B (Groups 4, 5, 6) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: Cmax of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate

Cmax of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK endpoints in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, Cmax for tedizolid metabolite in multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) and Part B (Groups 4, 5, 6) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: Tmax of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate

Tmax of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK endpoints in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, Tmax for tedizolid metabolite in multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) and Part B (Groups 4, 5, 6) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: t½ of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate

t½ of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. Protocol specified analysis of PK endpoints in Group 1 was done irrespective of age (28 days to \<24 months, across ages in Cohorts 1 and 2). As specified in the protocol, t½ for tedizolid metabolite in multiple dose (Part A Group 2 Cohort 2, Group 3 Cohort 2) and Part B (Groups 4, 5, 6) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing

Part A: AUC0-12 of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate [AUC0-last]

AUC0-last of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach used in this noncompartmental analysis allowed data collected to generate single concentration listing. This was analyzed in the per protocol population consisting of the subset of participants who complied with the protocol sufficiently to ensure that these data would be likely to exhibit treatment effects, based on the underlying scientific model and had data available for this endpoint. As specified in the protocol, AUC0-last for tedizolid metabolite in single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1; Part B \[Groups 4, 5, 6\]) were not included in this endpoint and have been reported separately in the record.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: Cmax of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate

Cmax of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach used in this noncompartmental analysis allowed data collected to generate single concentration listing. As specified in the protocol, Cmax for tedizolid metabolite in single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1; Part B \[Groups 4, 5, 6\]) were not included in this endpoint and have been reported separately in the record.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: Tmax of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate

Tmax of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach used in this noncompartmental analysis allowed data collected to generate single listing. As specified in the protocol, Tmax for tedizolid metabolite in single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1; Part B \[Groups 4, 5, 6\]) were not included in this endpoint and have been reported separately in the record.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: AUC0-inf of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate

AUC0-inf of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach to be used in this noncompartmental analysis would allow data collected to generate single concentration listing. However, protocol-specified PK sampling did not characterize the terminal elimination phase; therefore, AUC0-inf of tedizolid metabolite could not be estimated for multiple dose study arms (Part A Group 2 Cohort 2 and Part A Group 3 Cohort 2). As specified in the protocol, AUC0-inf for tedizolid metabolite in single dose (Part A Group 1\[Cohorts 1 and 2\],Group 2 Cohort 1, Group 3 Cohort 1; Part B\[Groups 4, 5, 6\]) were not included in this endpoint and have been reported separately in the record.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part A: t½ of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate

t½ of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach to be used in this noncompartmental analysis would allow data collected to generate single listing. However, protocol-specified PK sampling did not characterize the terminal elimination phase; therefore, t½ could not be estimated for multiple dose study arms (Part A Group 2 Cohort 2 and Part A Group 3 Cohort 2). As specified in the protocol, t½ for tedizolid metabolite in single dose (Part A Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 3 Cohort 1; Part B \[Groups 4, 5, 6\]) were not included in this endpoint and have been reported separately in the record.

Time frame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing

Part B: Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension [AUC0-last]

Time frame: 1, 3, 5, 8, 12, and 24 hours post start of dosing

Part B: AUC0-inf of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension

AUC0-inf of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach used in this noncompartmental analysis allowed data collected to generate single concentration listing. As specified in the protocol, AUC0-inf for tedizolid metabolite in Part A (Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 2 Cohort 2, Group 3 Cohort 1, Group 3 Cohort 2) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 3, 5, 8, 12, and 24 hours post start of dosing

Part B: Cmax of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension

Cmax of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach used in this noncompartmental analysis allowed data collected to generate single concentration listing. As specified in the protocol, Cmax for tedizolid metabolite in Part A (Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 2 Cohort 2, Group 3 Cohort 1, Group 3 Cohort 2) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 3, 5, 8, 12, and 24 hours post start of dosing

Part B: Tmax of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension

Tmax of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach used in this noncompartmental analysis allowed data collected to generate single listing. As specified in the protocol, Tmax for tedizolid metabolite in Part A (Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 2 Cohort 2, Group 3 Cohort 1, Group 3 Cohort 2) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 3, 5, 8, 12, and 24 hours post start of dosing

Part B: t½ of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension

t½ of tedizolid (metabolite) was quantified in participants receiving tedizolid phosphate. The per protocol statistical approach used in this noncompartmental analysis allowed data collected to generate single listing. As specified in the protocol, t½ for tedizolid metabolite in Part A (Group 1 \[Cohorts 1 and 2\], Group 2 Cohort 1, Group 2 Cohort 2, Group 3 Cohort 1, Group 3 Cohort 2) were not included in this endpoint and have been reported separately in the record.

Time frame: 1, 3, 5, 8, 12, and 24 hours post start of dosing

Secondary Outcomes

Number of Participants With an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing an AE was reported for each arm.

Time frame: Up to approximately 21 days

Number of Participants That Discontinued Study Treatment Due to an AE

Time frame: Up to approximately 3 days