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).
Brief Title
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)
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.
* 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.
Completion Date
Completion Date Type
Actual
Conditions
Gram-Positive Bacterial Infections
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.
* 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.
Inclusion 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;
* 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;
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
11 Years
Minimum Age
2 Years
NCT Id
NCT02750761
Org Class
Industry
Org Full Name
Merck Sharp & Dohme LLC
Org Study Id
1986-013
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Cmax of tedizolid phosphate in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2). Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug)
Outcome Time Frame
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.
Outcome Description
Time to reach peak plasma concentration (Tmax) of tedizolid phosphate in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2). Tedizolid phosphate concentrations were below the lower limit of quantification in Group 3 and Group 4. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug)
Outcome Time Frame
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.
Outcome Description
Area under the plasma concentration time curve (AUC) of tedizolid phosphate from time zero to last detectable measurement following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement
Outcome Time Frame
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.
Outcome Description
Area under the plasma concentration time curve (AUC) of tedizolid phosphate from time zero to infinity following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity
Outcome Time Frame
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.
Outcome Description
Terminal elimination half-life (T1/2) of tedizolid phosphate following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug)
Outcome Time Frame
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.
Outcome Description
CL of IV tedizolid phosphate in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2).
Outcome Measure
Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV)
Outcome Time Frame
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.
Outcome Description
CL/F of oral suspension tedizolid phosphate and its active metabolite, tedizolid, in participants ages 6 to \<12 years (Group 3) and 2 to \<6 years (Groups 4).
Outcome Measure
Clearance (CL/F) of Tedizolid Phosphate in Participants Who Received Oral Tedizolid Phosphate (Prodrug)
Outcome Time Frame
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
Outcome Description
Maximum observed drug concentration in plasma (Cmax) of tedizolid (active metabolite) following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite)
Outcome Time Frame
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.
Outcome Description
Time to reach peak plasma concentration (Tmax) of tedizolid (active metabolite) following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite)
Outcome Time Frame
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.
Outcome Description
Area under the plasma concentration time curve (AUC) of tedizolid (active metabolite) from time zero to last detectable measurement following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement
Outcome Time Frame
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.
Outcome Description
Area under the plasma concentration time curve (AUC) of tedizolid (active metabolite) from time zero to infinity following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity
Outcome Time Frame
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.
Outcome Description
Terminal elimination half-life (T1/2) of tedizolid (active metabolite) following administration of IV or oral dose. Pharmacokinetic sampling occurred at the following time points: Group 1 (6 to \<12 years): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (IV): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (6 to \<12 years): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (2 to \<6 years): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite)
Outcome Time Frame
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.
Outcome Description
CL of IV tedizolid phosphate and its active metabolite, tedizolid, in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2).
Outcome Measure
Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV)
Outcome Time Frame
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.
Outcome Description
CL/F of tedizolid, in participants ages 6 to \<12 years (Group 3) and 2 to \<6 years (Groups 4).
Outcome Measure
Clearance (CL/F) of Tedizolid (Active Metabolite) in Participants Who Received Oral Tedizolid Phosphate
Outcome Time Frame
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
Outcome Description
The area under the plasma concentration time curve (AUC) of tedizolid (active metabolite) from time zero to infinity following administration of IV or oral dose, normalized to dosage, was calculated. Per protocol, this outcome used pooled groups as follows: The IV Group pooled Groups 1 and 2, who received tedizolid phosphate via intravenous (IV) administration; the Oral Group pooled groups 3 and 4, who received tedizolid phosphate via oral administration. Pharmacokinetic sampling occurred at the following time points: Group 1 (part of the IV Group): Day 1 immediately after infusion and 1.5, 2, 3, 4, 6, 12, and 24 hours; Group 2 (part of the IV Group): Day 1 immediately after infusion and 3, 6, 12, 24 and 48 hours; Group 3 (part of the Oral Group): Day 1 at 1, 2, 3, 4, 6, 8, 12, and 24 hours after oral dose; Group 4 (part of the Oral Group): Day 1 at 3, 6, 9, 12, 24 and 48 hours after oral dose.
Outcome Measure
Dose Normalized Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity
Outcome Time Frame
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 Ids
Secondary Id
TR701-120
Secondary Id
2015-004595-29
Secondary Id
MK-1986-013
Secondary Outcomes
Outcome Description
An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Outcome Time Frame
Up to 9 days
Outcome Measure
Number of Participants Who Experienced at Least One Adverse Event
Outcome Description
An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Outcome Time Frame
1 day
Outcome Measure
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Outcome Description
Palatability of oral tedizolid phosphate suspension in participants ages 6 to \<12 years (Group 3) and 2 to \<6 years (Group 4). Palatability was assessed using a 5-point hedonic scale and spontaneous verbal judgment. This hedonic scale consists of 5 pictures of line drawn faces corresponding to very bad, bad, neither good nor bad, good and very good. The participant was asked to mark or point to the face to show how they felt about the taste of the study drug. For preverbal children, the score was assessed by the parent/caregiver, or study staff administering or witnessing administration of the study drug.
Outcome Time Frame
Following single oral dose on Day 1
Outcome Measure
Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
11
Minimum Age Number (converted to Years and rounded down)
2
Investigators
Investigator Type
Principal Investigator
Investigator Name
Iona Munjal
Investigator Email
imunjal@montefiore.org
Investigator Phone