Clinical trial NCT02750761: 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)
Official title: A Phase 1, Single-Administration Pharmacokinetic and Safety Study of Oral and IV Tedizolid Phosphate in Hospitalized Subjects 2 to <12 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gram-Positive Bacterial Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2016-04-25
Enrollment: 32
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug)
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug)
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug)
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV)
timeFrame: Group 1 (6 to <12 years): Day 1 immediately after infusion and at 1.5, 2, 3, 4, 6, 12, and 24 hours. Group 2 (2 to <6 years): Day 1 immediately after infusion and at 3, 6, 12, 24 and 48 hours.
measure: Clearance (CL/F) of Tedizolid Phosphate in Participants Who Received Oral Tedizolid Phosphate (Prodrug)
timeFrame: Group 3 (6 to <12 years): at 1, 2, 3, 4, 6, 8, 12, and 24 hours after the dose; Group 4 (2 to <6 years): at 3, 6, 9, 12, 24 and 48 hours after the dose
measure: Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite)
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite)
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite)
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
measure: Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV)
timeFrame: Group 1 (6 to <12 years): Day 1 immediately after infusion and at 1.5, 2, 3, 4, 6, 12, and 24 hours. Group 2 (2 to <6 years): Day 1 immediately after infusion and at 3, 6, 12, 24 and 48 hours.
measure: Clearance (CL/F) of Tedizolid (Active Metabolite) in Participants Who Received Oral Tedizolid Phosphate
timeFrame: Group 3 (6 to <12 years): at 1, 2, 3, 4, 6, 8, 12, and 24 hours after the dose; Group 4 (2 to <6 years): at 3, 6, 9, 12, 24 and 48 hours after the dose
measure: Dose Normalized Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity
timeFrame: IV: immediately after the end of the infusion, and various time points up to 48 hours after the start of infusion as described above. Oral: at various time points up to 48 hours after the dose as described above.
Secondary outcomes:
measure: Number of Participants Who Experienced at Least One Adverse Event
timeFrame: Up to 9 days
measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: 1 day
measure: Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate
timeFrame: Following single oral dose on Day 1
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Arrieta AC, Ang JY, Espinosa C, Fofanov O, Tondel C, Chou MZ, De Anda CS, Kim JY, Li D, Sabato P, Sears PS, Bradley JS. Pharmacokinetics and Safety of Single-dose Tedizolid Phosphate in Children 2 to <12 Years of Age. Pediatr Infect Dis J. 2021 Apr 1;40(4):317-323. doi: 10.1097/INF.0000000000003030.