Gram-Positive Bacterial Infections
Conditions
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.
Interventions
DRUGTedizolid Phosphate (IV)
200 mg/vial powder for injection
DRUGTedizolid Phosphate (oral suspension)
Powder for oral suspension 20 mg/mL following reconstitution
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Normalized Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 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. | 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. |
| Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite) | 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. | 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. |
| Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | 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. | 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). |
| Clearance (CL/F) of Tedizolid (Active Metabolite) in Participants Who Received Oral Tedizolid Phosphate | 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 | CL/F of tedizolid, in participants ages 6 to \<12 years (Group 3) and 2 to \<6 years (Groups 4). |
| Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug) | 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. | 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. |
| Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug) | 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. | 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. |
| Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement | 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. | 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. |
| Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity | 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. | 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. |
| Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug) | 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. | 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. |
| Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | 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. | CL of IV tedizolid phosphate in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2). |
| Clearance (CL/F) of Tedizolid Phosphate in Participants Who Received Oral Tedizolid Phosphate (Prodrug) | 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 | 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). |
| Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite) | 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. | 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. |
| Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite) | 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. | 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. |
| Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement | 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. | 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. |
| Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 1 day | 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. |
| Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Following single oral dose on Day 1 | 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. |
| Number of Participants Who Experienced at Least One Adverse Event | Up to 9 days | 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. |
Participant flow
Pre-assignment details
Prior to enrollment, participants were receiving prophylaxis for or with a confirmed or suspected infection with gram-positive bacteria and receiving concurrent antibiotic treatment with gram-positive antibacterial activity.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) Participants 6 to \<12 years of age received a single intravenous infusion of tedizolid phosphate dosed at 5 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate. | 5 |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) Participants 6 to \<12 years of age received a single intravenous infusion of tedizolid phosphate dosed at 4 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate. | 5 |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) Participants 2 to \<6 years of age received a single intravenous infusion of tedizolid phosphate dosed at 6 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate. | 5 |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) Participants 2 to \<6 years of age received a single intravenous infusion of tedizolid phosphate dosed at 3 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate. | 5 |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) Participants 6 to \<12 years of age received a single dose of tedizolid phosphate oral suspension dosed at 4 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate. | 6 |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) Participants 2 to \<6 years of age received a single dose of tedizolid phosphate oral suspension dosed at 3 mg/kg of total body weight. Maximum dose is 200 mg of tedizolid phosphate. | 6 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 8.2 years STANDARD_DEVIATION 1.3 | 7.4 years STANDARD_DEVIATION 1.1 | 3.4 years STANDARD_DEVIATION 0.5 | 4.0 years STANDARD_DEVIATION 1.4 | 8.5 years STANDARD_DEVIATION 1.8 | 3.2 years STANDARD_DEVIATION 1 | 5.8 years STANDARD_DEVIATION 2.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 4 Participants | 3 Participants | 5 Participants | 3 Participants | 4 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 26 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 4 Participants | 2 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 5 | 1 / 5 | 2 / 5 | 0 / 5 | 3 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 1 / 5 | 0 / 5 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid necessary to calculate the AUC.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 29600 hr*ng/mL |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 21000 hr*ng/mL |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 27300 hr*ng/mL |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 17300 hr*ng/mL |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 24900 hr*ng/mL |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 17200 hr*ng/mL |
Primary
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid necessary to calculate the AUC.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement | 28200 hr*ng/mL | 95% Confidence Interval 21200 |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement | 19700 hr*ng/mL | 95% Confidence Interval 14800 |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement | 26800 hr*ng/mL | 95% Confidence Interval 20200 |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement | 17100 hr*ng/mL | 95% Confidence Interval 12800 |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement | 22700 hr*ng/mL | 95% Confidence Interval 17500 |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Last Detectable Measurement | 14600 hr*ng/mL | 95% Confidence Interval 11200 |
Primary
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid phosphate necessary to calculate the AUC. Only 1 participant, from Group 2 Cohort 2, had analyzable data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity | NA hr*ng/mL |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity | NA hr*ng/mL |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity | NA hr*ng/mL |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity | 2000 hr*ng/mL |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity | NA hr*ng/mL |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Infinity | NA hr*ng/mL |
Primary
Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid phosphate necessary to calculate the AUC.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement | 64.8 hr*ng/mL |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement | 63.6 hr*ng/mL |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement | 433 hr*ng/mL |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement | 182 hr*ng/mL |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement | NA hr*ng/mL |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid Phosphate (Prodrug) From Time Zero to Last Detectable Measurement | 14.1 hr*ng/mL |
Primary
Clearance (CL/F) of Tedizolid (Active Metabolite) in Participants Who Received Oral Tedizolid Phosphate
CL/F of tedizolid, in participants ages 6 to \<12 years (Group 3) and 2 to \<6 years (Groups 4).
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
Population: All participants who received an oral dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid of tedizolid necessary to calculate the CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Clearance (CL/F) of Tedizolid (Active Metabolite) in Participants Who Received Oral Tedizolid Phosphate | 4073.32 mL/hr/kg | Geometric Coefficient of Variation 21.14 |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Clearance (CL/F) of Tedizolid (Active Metabolite) in Participants Who Received Oral Tedizolid Phosphate | 2090.77 mL/hr/kg | Geometric Coefficient of Variation 50.27 |
Primary
Clearance (CL/F) of Tedizolid Phosphate in Participants Who Received Oral Tedizolid Phosphate (Prodrug)
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).
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
Population: All participants who received an oral dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid phosphate necessary to calculate the CL/F. All orally dosed participants' data were below the lower limit of quantification, resulting in no reportable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Clearance (CL/F) of Tedizolid Phosphate in Participants Who Received Oral Tedizolid Phosphate (Prodrug) | NA mL/hr/kg |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Clearance (CL/F) of Tedizolid Phosphate in Participants Who Received Oral Tedizolid Phosphate (Prodrug) | NA mL/hr/kg |
Primary
Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV)
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).
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.
Population: All participants who received an IV infusion of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid of tedizolid necessary to calculate the CL.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | 4164.60 mL/hr | Geometric Coefficient of Variation 36.39 |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | 4145.73 mL/hr | Geometric Coefficient of Variation 73.21 |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | 2582.66 mL/hr | Geometric Coefficient of Variation 20.64 |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Clearance (CL) of Tedizolid (Active Metabolite) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | 2461.08 mL/hr | Geometric Coefficient of Variation 11.99 |
Primary
Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV)
CL of IV tedizolid phosphate in participants ages 6 to \<12 years (Group 1) and 2 to \<6 years (Group 2).
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.
Population: All participants who received an IV infusion of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid phosphate necessary to calculate the CL. Only 1 participant, from Group 2 Cohort 2, had analyzable data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | NA mL/hr |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | NA mL/hr |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | NA mL/hr |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Clearance (CL) of Tedizolid Phosphate (Prodrug) in Participants Who Received Tedizolid Phosphate Intravenously (IV) | 24400 mL/hr |
Primary
Dose Normalized Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid necessary to calculate the AUC. Per protocol, participant arms were pooled based on route of administration (IV or Oral) and outcome was normalized to the dose received.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Dose Normalized Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 5340 hr*ng/mL/mg/kg |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Dose Normalized Area Under the Plasma Concentration Time Curve (AUC) of Tedizolid (Active Metabolite) From Time Zero to Infinity | 6000 hr*ng/mL/mg/kg |
90% CI: [0.93, 1.35]
Primary
Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug)
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had at least one quantifiable (above the lower limit of quantification) post-administration concentration of tedizolid phosphate.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug) | 76.3 ng/mL |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug) | 82.4 ng/mL |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug) | 710 ng/mL |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug) | 234 ng/mL |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug) | NA ng/mL |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid Phosphate (Prodrug) | 9.4 ng/mL |
Primary
Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite)
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had at least one quantifiable (above the lower limit of quantification) post-administration concentration of tedizolid.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite) | 4960 ng/mL | 95% Confidence Interval 3440 |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite) | 4140 ng/mL | 95% Confidence Interval 2880 |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite) | 7460 ng/mL | 95% Confidence Interval 5180 |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite) | 4190 ng/mL | 95% Confidence Interval 2910 |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite) | 2590 ng/mL | 95% Confidence Interval 1860 |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Maximum Observed Drug Concentration in Plasma (Cmax) of Tedizolid (the Active Metabolite) | 1820 ng/mL | 95% Confidence Interval 1310 |
Primary
Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite)
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid necessary to calculate the T1/2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite) | 5.18 Hours | Geometric Coefficient of Variation 21.54 |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite) | 4.93 Hours | Geometric Coefficient of Variation 13.82 |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite) | 5.51 Hours | Geometric Coefficient of Variation 30.16 |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite) | 5.76 Hours | Geometric Coefficient of Variation 29.2 |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite) | 6.15 Hours | Geometric Coefficient of Variation 24.41 |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid (Active Metabolite) | 6.79 Hours | Geometric Coefficient of Variation 10.85 |
Primary
Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug)
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had adequate quantifiable (above the lower limit of quantification) post-administration concentrations of tedizolid phosphate necessary to calculate the T1/2. Only 1 participant, from Group 2 Cohort 2, had analyzable data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug) | NA Hours |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug) | NA Hours |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug) | NA Hours |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug) | 2.77 Hours |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug) | NA Hours |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Terminal Elimination Half-life (T1/2) of Tedizolid Phosphate (Prodrug) | NA Hours |
Primary
Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug)
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had at least one quantifiable (above the lower limit of quantification) post-administration concentration of tedizolid phosphate.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug) | 1.18 Hours |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug) | 1.10 Hours |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug) | 1.12 Hours |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug) | 1.02 Hours |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug) | NA Hours |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid Phosphate (Prodrug) | 6.0 Hours |
Primary
Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite)
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.
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.
Population: All participants who received a dose of tedizolid phosphate and had at least one quantifiable (above the lower limit of quantification) post-administration concentration of tedizolid.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite) | 1.18 Hours | Full Range 1.07 |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite) | 1.10 Hours | Full Range 1 |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite) | 1.12 Hours | Full Range 1.07 |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite) | 1.00 Hours | Full Range 1 |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite) | 2.53 Hours | Full Range 1.2 |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Time to Reach Peak Plasma Concentration (Tmax) of Tedizolid (the Active Metabolite) | 3.08 Hours | Full Range 3 |
Secondary
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
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.
Time frame: 1 day
Population: All participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
Secondary
Number of Participants Who Experienced at Least One Adverse Event
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.
Time frame: Up to 9 days
Population: All participants who received any study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Number of Participants Who Experienced at Least One Adverse Event | 2 Participants |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Number of Participants Who Experienced at Least One Adverse Event | 1 Participants |
| Group 2 Cohort 1: Tedizolid IV 6 mg/kg (2 to <6 Years) | Number of Participants Who Experienced at Least One Adverse Event | 2 Participants |
| Group 2 Cohort 2: Tedizolid IV 3 mg/kg (2 to <6 Years) | Number of Participants Who Experienced at Least One Adverse Event | 0 Participants |
| Group 3: Tedizolid Oral 4 mg/kg (6 to <12 Years) | Number of Participants Who Experienced at Least One Adverse Event | 3 Participants |
| Group 4: Tedizolid Oral 3 mg/kg (2 to <6 Years) | Number of Participants Who Experienced at Least One Adverse Event | 1 Participants |
Secondary
Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate
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.
Time frame: Following single oral dose on Day 1
Population: All participants who received an oral dose of tedizolid phosphate suspension.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Good | 0 Participants |
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Bad | 1 Participants |
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Neither good nor bad | 3 Participants |
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Very bad | 2 Participants |
| Group 1 Cohort 1: Tedizolid IV 5 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Very good | 0 Participants |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Very bad | 0 Participants |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Very good | 0 Participants |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Good | 1 Participants |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Neither good nor bad | 2 Participants |
| Group 1 Cohort 2: Tedizolid IV 4 mg/kg (6 to <12 Years) | Palatability of Oral Tedizolid Phosphate Suspension in Participants Who Received Oral Tedizolid Phosphate | Bad | 3 Participants |