Clinical trial NCT03217565: A Pharmacokinetic Study of Tedizolid Phosphate in Pediatric Participants With Gram-Positive Infections (MK-1986-014)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gram-Positive Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-07-14
Enrollment: 47
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

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.

Primary outcomes:
measure: 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
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: Maximum Concentration (Cmax) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: Time to Reach Maximum Concentration (Tmax) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: Apparent Terminal Half-life (t½) of Tedizolid Phosphate (Prodrug) After Single-dose IV Administration
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: AUC0-last of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: AUC0-inf of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: Cmax of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: Tmax of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: t½ of Tedizolid Phosphate (Prodrug) After Multiple-dose IV Administration
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: AUC0-24 of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate [AUC0-last]
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: AUC0-inf of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: Cmax of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: Tmax of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: t½ of Tedizolid (Active Metabolite) After Single-dose IV Administration of Tedizolid Phosphate
timeFrame: 1, 1.5, 3, 6, 12 and 24 hours post start of dosing
measure: Part A: AUC0-12 of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate [AUC0-last]
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: Cmax of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: Tmax of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: AUC0-inf of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: Part A: t½ of Tedizolid (Active Metabolite) After Multiple-dose IV Administration of Tedizolid Phosphate
timeFrame: Day 3: pre-dose, 1, 1.5, 3, 6 and 12 hours post start of dosing
measure: 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]
timeFrame: 1, 3, 5, 8, 12, and 24 hours post start of dosing
measure: Part B: AUC0-inf of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension
timeFrame: 1, 3, 5, 8, 12, and 24 hours post start of dosing
measure: Part B: Cmax of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension
timeFrame: 1, 3, 5, 8, 12, and 24 hours post start of dosing
measure: Part B: Tmax of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension
timeFrame: 1, 3, 5, 8, 12, and 24 hours post start of dosing
measure: Part B: t½ of Tedizolid (Active Metabolite) After Single-dose Administration of Tedizolid Phosphate Oral Suspension
timeFrame: 1, 3, 5, 8, 12, and 24 hours post start of dosing
Secondary outcomes:
measure: Number of Participants With an Adverse Event (AE)
timeFrame: Up to approximately 21 days
measure: Number of Participants That Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 3 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital ( Site 1012)
state: Arkansas
city: Orange
country: United States
facility: Children's Hospital of Orange County ( Site 1001)
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital ( Site 1021)
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1022)
state: Illinois
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Regional Medical Center. ( Site 1004)
state: Louisiana
city: Saint Louis
country: United States
facility: Saint Louis Children's Hospital ( Site 1020)
state: Missouri
city: Salt Lake City
country: United States
facility: Primary Children's Hospital ( Site 1000)
state: Utah
city: Sevlievo
country: Bulgaria
facility: Medical Center - 1- Sevlievo EOOD ( Site 2207)
state: Gabrovo
city: Kozloduy
country: Bulgaria
facility: MHAT Sv. Ivan Rilski EOOD ( Site 2201)
state: Vratsa
city: Burgas
country: Bulgaria
facility: UMHAT Deva Maria ( Site 2208)
city: Gabrovo
country: Bulgaria
facility: MHAT Dr. Tota Venkova-Pediatrics ( Site 2218)
city: Montana
country: Bulgaria
facility: MHAT "Dr. Stamen Iliev" Montana ( Site 2215)
city: Montana
country: Bulgaria
facility: MHAT City Clinic Sv. Georgi EOOD ( Site 2202)
city: Pleven
country: Bulgaria
facility: UMHAT Dr. Georgi Stranski EAD ( Site 2211)
city: Ruse
country: Bulgaria
facility: MHAT Rousse-Neonatology ( Site 2213)
city: Ruse
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Ruse ( Site 2204)
city: Ruse
country: Bulgaria
facility: UMHAT Kanev AD ( Site 2209)
city: Sliven
country: Bulgaria
facility: MHAT Dr. Ival Seliminski ( Site 2212)
city: Medellin
country: Colombia
facility: Hospital San Vicente Fundacion ( Site 1103)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Clinica de la Costa S.A.S. ( Site 1106)
state: Atlantico
city: Bogota
country: Colombia
facility: Fundacion Hospital Infantil Universitario de San Jose ( Site 1107)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Fundacion Valle del Lili ( Site 1102)
state: Valle Del Cauca
city: Loerenskog
country: Norway
facility: Akershus Universitetssykehus HF ( Site 1604)
state: Akershus
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus ( Site 1602)
state: Hordaland
city: Stavanger
country: Norway
facility: Stavanger Universitetssykehus, Helse Stavanger ( Site 1601)
state: Rogaland
city: Trondheim
country: Norway
facility: St. Olavs Hospital. ( Site 1600)
state: Sor-Trondelag
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust ( Site 1700)
state: Hampshire
city: Liverpool
country: United Kingdom
facility: Alder Hey Childrens NHS Foundation Trust Hospital ( Site 1703)
state: Lancashire
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary ( Site 1702)
state: Newcastle Upon Tyne
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust ( Site 1704)
state: Oxfordshire
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: