MK-1986-013

Principal Investigator: Kwabena Ampofo
Keywords: tedizolid phosphate Department: Pediatric Administration
IRB Number: 00102349 Co Investigator:  
Specialty: Pediatrics, General
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Taylor Mathie
taylor.mathie@hsc.utah.edu
801-587-6293

Brief Summary

Primary Objective
Part A (IV Study Drug Administration)
To describe the single-administration PK of IV tedizolid phosphate and its active
metabolite, tedizolid, in subjects ages 6 to <12 years (Group 1) and 2 to <6 years (Group
2).

Part B (Oral Study Drug Administration)
To describe the bioavailability of tedizolid following oral tedizolid phosphate administration
to subjects ages 6 to <12 years (Group 3) and 2 to <6 years (Group 4).

Secondary Objective
Part A (IV Study Drug Administration)
To evaluate the safety and tolerability of IV tedizolid phosphate administration in subjects ages
6 to <12 years (Group 1) and 2 to <6 years (Group 2).

Part B (Oral Study Drug Administration)
To evaluate the safety and tolerability of oral tedizolid phosphate administration in subjects
ages 6 to <12 years (Group 3) and 2 to <6 years (Group 4).
To evaluate the palatability of oral tedizolid phosphate suspension in subjects ages 6 to <12
years (Group 3) and 2 to <6 years (Group 4).

This is an open-label, multicenter, 2-part, single-administration study to assess the 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 (Part B) administration to hospitalized
subjects ages 6 to <12 years (Groups 1 and 3, respectively), and 2 to <6 years (Groups 2 and
4, respectively). Subjects receiving prophylaxis for or being treated for a confirmed or
suspected infection with Gram-positive bacteria will be enrolled. The IV groups will be split
into 2 cohorts of 5 subjects each. Prior to this amendment, 5 subjects ages 6 to <12 from
Cohort 1 of Group 1 received the study drug at dose of 5 mg/kg of total body weight. Table 3
summarizes the parts (administration route), groups (age), and cohorts (dose) of the amended
study.

Tedizolid phosphate will be administered to subjects any time after antimicrobial
administration with a non-study antibiotic has been initiated.

Progression to younger ages will be conducted as follows:

The first group to be enrolled will be Group 1 Cohort 1; following enrollment of all 5
patients in this cohort, a preliminary analysis will take place to review the
pharmacokinetic and safety data. The dose for further subjects in this group (Group 1
Cohort 2) as well as Group 3 (oral) may be adjusted, if the safety data suggest poor
tolerability or the PK data indicate a low likelihood of achieving exposure distribution
similar to that at the indicated dose in adults. These data will also be used to reevaluate
the dose for the younger age range (2 to <6 years), prior to initiating Group 2
Cohort 1. The younger age range will follow a similar sequence, with a preliminary
analysis of PK and safety after the first cohort of Group 2 has been enrolled, in order to
confirm or adjust the dose for the remaining subjects in this age range (Group 2 cohort
2 and Group 4).


Prior to this amendment, the first 5 subjects were enrolled for Group 1 Cohort 1, and
the preliminary analysis of the safety data indicate that the 5 mg/kg dose is well
tolerated. Pharmacokinetic analyses are underway to evaluate the appropriate dose level
for further subjects in both age ranges. (The modified dose level will be communicated
to sites via a memo and a revised Pharmacy Manual.).


Further enrollment in the upper age range will initiate with group 3 (oral), to provide an early
assessment of bioavailability (which enables additional studies to be initiated), prior to enrolling
the remainder of the IV Group 1. A similar sequence of enrollment (IV Group 2 Cohort 1, Oral
Group 4, IV Group 2 Cohort 2) will be used for enrollment of the lower age group.

In addition to safety (clinical laboratory evaluations; physical examinations; adverse events),
palatability will be assessed in oral tedizolid phosphate suspension in subjects ages 6 to <12
years (Group 3) and 2 to <6 years (Group 4). Subjects will receive study drug on Day 1, with
study visits on Day 2 and Day 8. The Day 8 Visit may be a telephone contact.

Study treatment may be discontinued at the subject’s/Parent's/Guardian's request, in the case of
unacceptable toxicity or pregnancy, or if the Investigator believes changing therapy would be
in the best interest of the subject.

The overall duration of the study is expected to be approximately 24.5 months (24 months for
enrollment, 11 days from the Screening Visit through last visit [Study Day 8]). Subject
participation may be extended if a subject is being monitored for an SAE. Subjects will be
monitored for AEs through 7 days after study drug administration and SAEs will be followed
until stabilization, resolution/death, or consent/assent is withdrawn.

Inclusion Criteria

1. Aged 2 to <12 years at the time of consent


2. Receiving prophylaxis for or with a confirmed or suspected infection with Gram-positive bacteria and receiving concurrent antibiotic treatment with Gram-positive antibacterial activity


3. Weight >5th percentile and <95th percentile based on age (http://www.cdc.gov/growthcharts/clinical_charts.htm)


4. Stable condition as determined from medical history, physical examination, electrocardiogram (minimally 5-lead), vital signs, and clinical laboratory evaluations


5. No clinically significant ECG abnormalities in the judgment of the Investigator


6. Serum creatinine within 1.5 × upper limit of reference range based on age


7. Females must be pre-menarchal, abstinent, or practicing an effective method of birth control


8. Negative blood or urine beta-human chorionic gonadotropin pregnancy test (if urine test is used, it must be high sensitivity [i.e., able to detect 10 mIU/mL β-hCG]) at the Screening Visit (postmenarchal females only)


9. Subjects and parents must be willing to adhere to the prohibitions and restrictions specified in this protocol


10. Parents or guardians able to give informed consent and willing and able to comply with all required study procedures. Assent is also required of children capable of understanding the nature of the study (typically ≥7 years old)

Exclusion Criteria

1. 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 interpretation of the study results, as determined by the Investigator


2. Use of rifampin within, 14 days prior to study drug administration


3. Use of ranitidine, cimetidine, and antacids for subjects in Part B (oral administration) from 24 hours prior to study drug administration and throughout the study


4. Recent (3 month) history or current infection with viral hepatitis or other significant hepatic disease


5. History of drug allergy or hypersensitivity to oxazolidinones


6. Pregnant or breast feeding


7. Significant blood loss (≥5% of total blood volume) within 60 days before the Screening Visit


8. Any acute or chronic condition that, in the opinion of the Investigator, would limit the subject’s ability to complete and/or participate in this clinical study


9. Treatment with investigational medicinal product within 30 days before the infusion/dose of study drug


10. Need for 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.)


11. 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